Inquiry into Matters Relating to the Safety of Blood ...€¦ · EXECUTIVE SUMMARY REPORT OF THE...
84
3 Inquiry into Matters Relating to the Safety_of Blood Products in New Zealand Wellington December 1992 Department of Health TETARI ORA
Transcript of Inquiry into Matters Relating to the Safety of Blood ...€¦ · EXECUTIVE SUMMARY REPORT OF THE...
3
Inquiry into MattersRelating to the
Safety_of Blood Productsin New Zealand
WellingtonDecember 1992
Department of HealthTETARI ORA
Dr Sue MoreyMember of the Inquiry
Hon. Stan RodgerMember of the Inquiry
00, 0
Mr. J. C. LovelaceDirector-General of HealthDepartment of HealthWellington
Dear Mr. Lovelace,
In accordance with the Terms of Reference of the Inquiry into matters relating to the safety ofblood products in New Zealand, we have the honour to present our report.
WELLINGTON15 December 1992
EXECUTIVE SUMMARY
REPORT OF THE INQUIRY INTO MATTERS RELATINGTO THE SAFETY OF BLOOD PRODUCTS IN NEW ZEALAND
1Issue which led to the InquiryOn 17 November, an article in the "Dominion" newspaper raised concern about the continuedsupply, after HCV screening was introduced in July 1992, of the blood product Factor IX(Prothrombinex) which was manufactured from blood unscreened for Hepatitis C, resulting inpotential risk of Hepatitis C infection for haemophiliacs using Factor IX.
2Establishment of Inquiry and Tennis of ReferenceThe Director-General by letter dated 23 November 1992 appointed the Inquiry under Section 7 ofthe Health Act 1956 and Section 90 of the Area Health Boards Act 1983. Dr Sue Morey, ChiefMedical Officer, New South Wales Department of Health, Australia and the Honourable StanleyJoseph Rodger, retired Member of Parliament and former Minister of the Crown, were charged asfollows:
"Now pursuant to section 7 of the Health Act 1956 and section 90 of the Area Health Boards Act1983 you are appointed and requested to do the following:
1 To determine the circumstances surrounding the continued supply after 1 July 1992 of ablood product which potentially exposed the users of that product to the risk of infectionwith Hepatitis C; and
2 To investigate what are the responsibilities and functions of the Office of the Minister ofHealth, the Department of Health, the Blood Transfusion Advisory Committee and theRegional Blood Transfusion Services and how those functions and responsibilities inter-relate in respect of:2.1The provision of policy advice to the Minister of Health regarding the risk ofinfection with Hepatitis C resulting from receipt of fractionated blood products; and2.2The facilitation of the efficient and effective and safe acquisition and distribution offractionated blood products in New Zealand.
3Report to the Director-General of Health on the results of your inquiry makingrecommendations as appropriate regarding:3.1Any changes to processes for the preparation and submission to the Minister ofHealth of policy advice relating to blood and blood products; and3.2 Any changes to the responsibilities and functions between the office of the Ministerof Health, the Department of Health, the Blood Transfusion Advisory Committee and theRegional Blood Transfusion Service and their inter-relationships that are necessary tofacilitate the acquisition and distribution of blood and blood products in an efficient andeffective and safe way (bearing in mind the Government's proposals for the reorganisationof the Blood Transfusion Service).
3Procedure Adopted b y the Inquiry
3.1 The Inquiry reviewed the functions and responsibilities of the Office of the Minister ofHealth, the Department of Health (including changes arising from departmental restructuring), theBlood Transfusion Advisory Committee and the Regional Blood Transfusion Services. The rolesand inter-related responsibilities of the Communicable Disease Control Advisory Committee andthe Medicines Adverse Reactions Committee were also considered.
3.2 The Inquiry examined departmental files for all relevant correspondence, backgroundpapers and briefing papers to Ministers, the Minutes of the relevant advisory committees andinterviewed departmental and ministerial office staff, in order to establish a chronology of events.
3.3A number of interviews were held and submissions were received from a variety oforganisations and individuals.
4General Observations
Funding for screening of donated blood for Hepatitis C was provided from 1 July 1992. As aresult of timing of approval and time required for the tendering process and implementation,screening of blood for Hepatitis C was not in place throughout the country until 27 July 1992.
Because the time difference between plasma collection and product return for Factors VIII and IXis up to nine months, from 1 July until 30 November 1992, blood products supplied for clinicaluse in patients with haemophilia continued to be that made from blood unscreened for Hepatitis C.In the case of patients with Haemophilia A, as the products had been subjected to high heattreatment (80°C), any Hepatitis C virus in the plasma used to make the product would have beeninactivated. However, for patients with Haemophilia B (Factor IX deficiency) there was no
-'readily available product which could guarantee absence of potential exposure to the Hepatitis Cvirus.
Neither the Minister of Health nor senior officers of the Department of Health had beenspecifically alerted to the fact that, despite introduction of screening of blood donations, there wasa small group of patients, ie those with Factor IX deficiency, who had not been previouslyinfected with Hepatitis C (a total of between 10 and 15 patients) who were potentially exposed tothe virus if they received Factor IX. This is clearly a small subsection of a very vulnerable groupof patients, already carrying a significant burden of illness, and they warrant special attention.
Even if they had been specifically alerted to the fact that blood products derived from bloodunscreened for Hepatitis C were still in use, no clearly defined and completely satisfactoryalternative was available. High heat treated Factor IX (Prothrombinex H-T, PTX H-T) has notbeen available to either Australian or New Zealand patients because it is a new product which hasnot yet been approved by the Australian Drug Evaluation Committee, and there is a prohibition onthe export of products which are not licensed. (This unlicensed product was however madeavailable to New Zealand on 30 November 1992 at the request of the New Zealand Department ofHealth).
While the letter of 31 July 1992 to the Minister of Health written by Dr E W Berry on behalf ofthe Medical Advisory Panel of the New Zealand Haemophilia Society referred to the potential
2
problem for Factor IX deficient haemophiliacs associated with the lack of PTX-HT, the primarypurpose of the letter was to request funding to import products from overseas. The Minister'sreply of 4 September 1992 referred to the fact that Area Health Boards have the responsibility toprovide services for the health needs of the people of their region. While any Area Health Boardhas the ability to buy commercial products which have been high heat treated (or equivalent newproducts) from overseas, the fact that these products are derived from unknown plasma which maycontain unrecognised viruses is a cause for concern in scientific communities.
There is no doubt that much of the media attention to this issue has been inaccurate and misleadingand has led to unnecessary anxiety for the New Zealand public.
Nevertheless, the circumstances surrounding events subsequent to 1 July 1992 can only be placedin perspective by acknowledging that there has been widespread community concern and debateregarding testing of donated blood for Hepatitis C in New Zealand since early 1990.
The Blood Transfusion Advisory Committee advised the Department of Health in June 1990 andthe Communicable Disease Control Advisory Committee advised the Minister of Health in August1990 that screening of donated blood for Hepatitis C should be introduced. The matter wasrefel-red to the Department of Health which commissioned a number of cost-effectiveness studies.The Department was apparently concerned that the sensitivity and specificity of the available testwere not sufficiently high for this to be introduced at a time of significant budgetary problems forArea Health Boards. Approval in principle for the provision of central funding for theintroduction of Hepatitis C screening was given by the Minister of Health on 30 July 1991.Additional funds were sought through normal budgetary processes, but this application for fundingwas rejected, with approval of funding only recommended if funding was available fromreprioritisation within the Health Budget. Funds were withheld centrally from AHB Budgets toallow screening to commence in the 1992-93 financial year.
This two year delay was a cause of considerable concern to transfusion services, clinicians and thegeneral community, and was the subject of ongoing representations to the Minister and theDepartment. It is not difficult to see how the larger group of transfusion recipients in generaldetracted attention from the greater risk posed to the much smaller number of potential recipientsof unscreened, non high heat treated Factor IX . At no time was it clearly articulated that eventhe second generation screening test was only 98% sensitive, and would not detect 2 of every 100infected donors. • Therefore, when up to 6,000 donations were pooled to make one batch ofFactor IX, given the estimated prevalence of 0.31% of Hepatitis C in the donor population, 33%of batches are likely to contain Hepatitis C virus. In the absence of super heat treatment, over aperiod of time, all recipients of Factor IX are likely to become infected.
It is obvious that the complexities of the problem are unlikely to be recognised by those without amedical and scientific background. The fact that the Department of Health was undergoing anumber of major restructures during the period and that there was no medical or epidemiologicalinput from within the Department at decision making level, no doubt contributed to the delay inintroducing screening. There was no clear channel of communication between the Minister'sexpert Advisory Committees and the Minister, and the Departmental structures for providingadvice to the Minister on competing priorities lacked clinical input.
3
The devolution of responsibility and funding to Area Health Boards resulted in a failure toacknowledge that there are some clinical areas, blood transfusion being one, where strong nationalpolicy and national standards are essential. It is clear that at least in the foreseeable future, NewZealand will remain dependent on other countries for some blood products or recombinantproducts as they become available and that responsibility for negotiating and purchasing should bevested in an organisation with a clearly defined national responsibility in this area.
5Findings
5.1First Term of Reference
Blood and blood products can never be 100% safe - that is, there can never be a zero-riskblood supply.
HCV screening of blood reduces, but does not completely eliminate the risk of HCVinfection in blood.
Supply of Prothrombinex, a complex Factor IX blood clotting product, which was madefrom plasma unscreened for Hepatitis C, continued after 1 July 1992.
Screening of blood for HCV, begun on 27 July 1992, would have reduced the risk but noteliminated the possibility of infection. As the screening test will not detect 2 in every 100infected donors, and as up to 6,000 donations are pooled to make one batch of PTX, in theabsence of super heat treatment, 33% of batches are likely to contain HCV.
HCV in Factor IX is partially inactivated if the blood product heated to 60°C and morefully inactivated if the product is high heat treated to 80°C.
No approved and licensed alternative Factor IX product (heated to 80°C) was available ineither Australia or New Zealand on 1 July. An unregistered Australian product wasprovided under special conditions on 1 December 1992.
• The fact that Prothrombinex made from blood unscreened for Hepatitis C continued to beused after July 1, 1992 was not known either to the senior management of the Departmentof Health or to the Minister of Health or his office.
•There is no evidence of a deliberate attempt to withho l d information relating to thissituation.
5.2Second Term of reference
•There are no clearly defined lines of communication for transmission of policy advice to theMinister on issues relating to blood transfusion.
•BTAC was left without a Chairman or access to senior levels of the Department of Health orto the Minister of Health.
4
• As a result of numerous departmental reorganisations, there was no senior departmentalofficer with a knowledge of clinical issues, who was aware of the problems faced by BTACand the complex scientific problems involved in maintaining a safe and effective supply ofblood products in New Zealand.
•
Responsibility for negotiation with CSL for the acquisition and distribution of fractionatedblood products in New Zealand was loosely delegated to the Director of the Auckland RBTS.
•
There is no formal contract between CSL and New Zealand for the supply of blood productsworth over $6 million per year.
5.3Third term of reference
•There should be a Committee charged with the development of national policy andstandards for the Blood Transfusion Service. This Committee should compriserepresentatives from blood transfusion service directors, clinical haematologists, RegionalHealth Authorities, the Principal Medical Advisor, Department of Health and a consumer.
• The Committee should more appropriately advise the Director-General of Health ratherthan the Minister of Health in order to ensure that appropriate policy can be developedtaking into account other competing priorities.
•
Nevertheless, the Committee should retain the option to approach the Minister of Healthdirectly on matters of concern.
•
There are some distinctive features about Blood Transfusion Services which require them tobe considered in a somewhat different context from most other health services.
• There is a need for the services to retain a local focus, firstly to facilitate donor recruitmentand retention, and secondly to maintain close relationships with clinicians, the users of theproducts, in order to ensure appropriate usage and quality control.
There is also a need for a strong national focus.
- National standards for good manufacturing practice of blood and blood productsneed to be adopted and monitored.
- Decisions on policy for issues such as screening need to be made at a national level.
- There needs to be a clearly identified body which takes total responsibility for allissues relating to the acquisition and supply of blood and related products for NewZealand.
- There are likely to be financial as well as quality advantages in purchasing bloodproducts nationally.
5
Transfusion medicine is a highly specialised and rapidly advancing field. It is important tolimit responsibility for transfusion services to a small number of appropriately qualified staffwhose expertise can be maintained and developed
Links should be maintained between any body charged with the development of nationalblood transfusion policy and the Principal Medical Advisor to the Department to ensure thatsenior departmental officers are aware of any developing issues requiring a policy response.
.A contract should be signed with CSL, with regular review at appropriate intervals, toformalise the arrangements between Australia and New Zealand.
6Recommendations
There is a need for a national committee to take responsibility for the development ofpolicy and standards, the monitoring of standards and the provision of advice to theDepartment and the Minister of Health on issues relating to blood and blood products.
2The Principal Medical Advisor to the Department of Health should be responsible, withinthe Department of Health, for overseeing issues relating to blood and blood products.
3A contract should be formalised with CSL for the supply of blood products for use in NewZealand.
4 The Department of Health should request the manufacture and supply of high heat treatedProthrombinex, sourced from New Zealand plasma screened for HCV, from CSL at theearliest practicable opportunity.
5Steps should be taken by the Department of Health to ensure appropriate medical andtechnical input into health policy.
To:The Director-General of Health
REPORT OF THE INQUIRY INTO MATTERS RELATING TO THESAFETY OF BLOOD PRODUCTS IN NEW ZEALAND
Issue which led to the Inquiry
On 17 November, an article in the "Dominion" newspaper raised concern about thecontinued supply, after HCV screening was introduced in July 1992, of the bloodproduct Factor IX (Prothrombinex) which was manufactured from blood unscreenedfor Hepatitis C, resulting in potential risk of Hepatitis C infection for haemophiliacsusing Factor IX.
2Establishment of Inquiry and Terms of Reference
The Director-General by letter dated 23 November 1992 appointed the Inquiryunder Section 7 of the Health Act 1956 and Section 90 of the Area Health BoardsAct 1983. Dr Sue Morey, Chief Medical Officer, New South Wales Department ofHealth, Australia and the Honourable Stanley Joseph Rodger, retired Member ofParliament and former Minister of the Crown, were charged as follows:
"Now pursuant to section 7 of the Health Act 1956 and section 90 of the AreaHealth Boards Act 1983 you are appointed and requested to do the following:
1 To determine the circumstances surrounding the continued supply after 1July 1992 of a blood product which potentially exposed the users of thatproduct to the risk of infection with Hepatitis C; and
2 To investigate what are the responsibilities and functions of the Office of theMinister of Health, the Department of Health, the Blood TransfusionAdvisory Committee and the Regional Blood Transfusion Services and howthose functions and responsibilities inter-relate in respect of:
2.1 The provision of policy advice to the Minister of Health regardingthe risk of infection with Hepatitis C resulting from receipt of fractionatedblood products; and
2.2The facilitiation of the efficient and effective and safe acquisition anddistribution of fractionated blood products in New Zealand.
INQUIRY REPORT
3Report to the Director-General of Health on the results of your inquirymaking recommendations as appropriate regarding:
3.1Any changes to processes for the preparation and submission to theMinister of Health of policy advice relating to blood and blood products; and
3.2 Any changes to the responsibilities and functions between the officeof the Minister of Health, the Department of Health, the Blood TransfusionAdvisory Committee and the Regional Blood Transfusion Service and theirinter-relationships that are necessary to facilitate the acquisition anddistribution of blood and blood products in an efficient and effective and safeway (bearing in mind the Government's proposals for the reorganisation ofthe Blood Transfusion Service).
The Inquiry was assisted by Mr Patrick Hoy, Auditor - Major Projects Group,Office of the Controller and Auditor General, Wellington.
Support was also provided by the following officials of the Department of Health,Dr Sharon Kletchko, Wendy Edgar, Alison Brieseman and Gina Inglis.
We record our warm appreciation for their strenuous efforts in assisting to bring thisreport to the stage of presentation at very short notice.
INQUIRY REPORT 2
3Procedure Adopted by the Inquiry
3.1 The Inquiry reviewed the functions and responsibilities of the Office of theMinister of Health, the Department of Health (including changes arising fromdepartmental restructuring), the Blood Transfusion Advisory Committee and theRegional Blood Transfusion Services. The roles and inter-related responsibilities ofthe Communicable Disease Control Advisory Committee and the Medicines AdverseReactions Committee were also considered.
3.2 The Inquiry examined departmental files for all relevant correspondence,background papers and briefing papers to Ministers, the Minutes of the relevantadvisory committees and interviewed departmental and ministerial office staff, inorder to establish a chronology of events.
3.3 A number of interviews were held and submissions were received from avariety of organisations and individuals. A list of those interviewed or who madesubmissions is attached as Appendix 1.
4Clinical and Scientific Background Information
4.1Transfusion-transmitted Infection and Reduction of Risk
Transfusion of human blood is not without risk. Certain infectious agents includingmalaria, syphilis, hepatitis A, B & C, HIV and cytomegalovirus can be carried inthe blood and therefore transmitted during the transfusion process. In addition tothese (described in Appendix 4), at different times it has been alleged that morbilli,varicella, variola, epidemic parotitis, influenza, filariasis, toxoplasmosis, Q-fever,tuberculosis, leptospirosis and "Chagas" disease have been transmitted by bloodtransfusion.
The number of infections that are potentially transmissable by blood transfusionseems daunting, however, the incidence of most of these infections in the generalpopulation is low.
Five key measures help improve the safety of blood transfusions:
Selection of donors - it is important that donors are interviewed in private byexperienced interviewers, who will question the potential donor on relevantareas of their history and lifestyle. It is also important that there is anopportunity for a donor to request anonymously, subsequent to donation,that the blood not be used.
INQUIRY REPORT 3
2 Use, wherever possible, of autologous blood, that is blood donated by aperson for their own subsequent use. This would include salvaging and re-infusion of blood during surgical procedures.
3Education of providers to minimise use of blood transfusions as a treatmentoption unless the situation is life-threatening.
4Screening of blood for known infections. Laboratory-testing can identifymarkers of infectious agents in donated blood. Tests include those forsyphilis, hepatitis B and C viruses, HIV types 1 and 2, and human T-celllymphotropic virus (HTLV) types I and II; in addition, selected bloodcomponents may be tested or processed to prevent the transmission ofcytomegalovirus to susceptible patients.
5 Pooled plasma products can be subject to viral-inactivation procedures andresearch is under way on recombinant products and viral inactivation forcellular blood components.
The safety of the blood supply continues to improve. New screening tests areintroduced from time to time. The sensitivity of current tests continues to improve.There is also an increased awareness amongst the donor population of theirresponsibility when donating blood.
The chances of contracting a serious disease or dying from transfusion are nowmuch lower than with many other therapeutic interventions. However a zero-riskblood supply is virtually unachievable. Each step towards the goal of achieving azero-risk blood supply absorbs more resources that, if diverted elsewhere, mighthave a greater impact on the health of the public.
There is no consistent approach to dealing with this difficult question, but thereremains a responsibility to educate the public about the risks and benefits associatedwith blood transfusion.
Patients are at a much greater risk if they do not have transfusions when theygenuinely need them than they are from the possible complications of transfusion.
4.2Hepatitis C
Hepatitis is an inflammation of the liver commonly caused by viruses and toxicagents such as alcohol and other drugs. Recent advances in the identification of thecausative viral agents of hepatitis have clarified some of the issues and associatedproblems. The group of viruses causing hepatitis includes a range of very differentand unrelated human pathogens. Hepatitis A, hepatitis B, Epstein-Barr. hepatitis(associated with glandular fever) and cytomegalic hepatitis were until recently themajor identifiable forms of viral hepatitis. A further group was given theuncomfortable name of non A, non B hepatitis viruses.
INQUIRY REPORT 4
One of the major viruses causing non A, non B hepatitis is now designated HepatitisC. It is the most common form of hepatitis following blood transfusion and can bespread in ways other than through blood. Hepatitis D virus (also referred to asDelta agent) can cause infection only in association with hepatitis B and therefore isof special significance because of the high level of hepatitis B infection in NewZealand. The most recent advance is the successful identification of the viruscausing enterically transmitted non A, non B hepatitis, provisionally named hepatitisE virus (which has epidemiological and clinical features similar to hepatitis A).
The importance of sexual and perinatal transmission of Hepatitis C is uncertain. Itis clear, however, that it is transmitted through blood and blood products in thesame way as other blood-borne viruses, such as hepatitis B and humanimmunodeficiency virus (HIV). Hepatitis C occurs only occasionally in people whohave received blood transfusions. It is a more common problem in people receivinga lot of blood and blood products. Since the end of July 1992 all donated blood inNew Zealand has been screened for Hepatitis C, so blood transfusion has becomesafer.
It is thought that the majority of Hepatitis C infection in the community is caughtthrough ways other than transfusion of blood and blood products (e.g. sharing ofcontaminated needles and syringes by injecting drug users). In many cases it is notpossible to ascertain how the infection was acquired.
A great deal of information about Hepatitis C has become available internationallyin the last two years. Although several research studies are in progress, there islimited knowledge of the epidemiology and clinical spectrum of the disease in NewZealand.
The majority of cases of non A, non B hepatitis transmitted through bloodtransfusions and a significant proportion of cases of sporadic (no identified riskfactors) non A, non B hepatitis are thought to be due to infection with the HepatitisC virus.
Modes of transmission of Hepatitis C virus (HCV) in New Zealand are similar toother parts of the world. A number of studies have been carried out to look atprevalence of infection, although no national seroprevalance study has beenundertaken. All of the studies have investigated prevalence of antibody to HepatitisC Virus (anti-HCV). The presence of anti-HCV indicates that the person has beenexposed to the virus. It does not identify acute or chronic infection or whether theperson is immune.
Some of the results of serological study in NZ population groups provided by theNew Zealand Communicable Disease Centre are as follows:
Injecting drug users >75%anti-HCVreactive(mostly those attending treatment clinics):
INQUIRY REPORT
CLARIFICATION TO PARAGRAPH 3 ON PAGE 6 OF THE INQUIRY REPORT
Hepatitis C disease is not specifically listed in the First Schedule to the Health Act 1956but would be included in the category of Hepatitis non A or B.
People in the Christchurch community 15% anti-HCV reactivewith some liver dysfunction:
Patients with chronic liver disease: 10-20%anti-HCVreactive
STD clinic attenders: 7% anti-HCV reactive
Male prison inmates: 20% anti-HCV reactive
There were 585 laboratory-diagnosed anti-HCV positives in the first ten months of1992. There were also 157 cases found to have HCV RNA (a marker for the virusand therefore of infectivity.) Many of the RNA positive cases will have been anti-HCV positive as well.
Hepatitis C is not a notifiable disease. However up to 31 October 1992, notificationof hepatitis non A, non B, Hepatitis C or hepatitis acute type unspecified, numbered78. The notifications were only 13 in 1990 and 22 in 1991. The increasedreporting in 1992 is likely to be due to increased awareness of Hepatitis C.
Australian figures suggest that about 40% of patients with chronic HCV infectionreferred to clinics acquired the infection from transfusion of blood and bloodproducts; compared with 40% by injecting drug use and 20% other factors(including tattooing and occupational exposure.) In contrast, information from theUSA suggests that 10% of cases of non-A, non-B hepatitis is related to transfusion.The proportion of New Zealand cases of Hepatitis C associated with transfusion ofblood or blood products is likely to be between these estimates.
Up to 50% of adults who are infected with HCV may become chronic carriers ofthe virus. This compares with hepatitis B, where up to 10% of adolescents andadults, and 50% or more of neonates and pre-schoolers infected develop a chroniccarrier state.
Most patients with chronic HCV infection do not initially show any symptoms ofillness (they are asymptomatic) but many gradually develop non-specific symptomssuch as fatigue and malaise. Chronic carriers are rarely jaundiced.
Hepatitis C virus carriers have a substantially increased risk of developing chronicliver disease, including chronic persistent hepatitis, chronic active hepatitis,cirrhosis and primary hepatocellular carcinoma. Progression to chronic diseases isusually very slow, occurring over 1-3 decades.
Asymptomatic or symptomatic patients may have normal or intermittently abnormalblood biochemical findings and have specific inflammatory activity in the liverwhich can only be identified by liver biopsy. The latter is particularly important inrelation to monitoring therapy with drugs such as Interferon.
INQUIRY REPORT 6
The outcomes of HCV infection may be influenced by other factors, such asalcohol.
4.3 Haemophililia
Haemophilia is a term which describes a congenital plasma clotting deficiency ordefect which may result in bleeding into muscles, joints and body cavities, hours ordays after an acute trauma.
Most of the inherited plasma coagulation disorders are due to defects in singlecoagulation proteins (those proteins responsible for helping blood to clot).
Two of the disorders, namely factors VIII and IX deficiency, occur in males but arecarried by females (X chromosome-linked). These two disorders account for themajority of congenital coagulation disorders. That is, most people with haemophiliain New Zealand have one or other of these disorders. These patients merit specialattention since they may have severe bleeding and chronic disability and requirespecialised medical therapy with pooled plasma products for either prophylaxis toprevent bleeding or to control bleeding.
Prothombinex has been a standard product for the management of patients withFactor IX deficiency for many years. It contains coagulation factors II, IX and Xwith atrace of VII.
4.4 Estimated Risk from Blood and Blood Products of Hepatitis C
A number of media reports have contained misleading figures regarding thepotential risk of infection with HCV to New Zealanders. The following informationattempts to put this risk into perspective.
There are 135,000 patients transfused per year who are at risk of infection. Thismeans that 337,500 patients will have been transfused from February 1990 (whenAustralia began to screen) to 27 July 1992 (when New Zealand began to screen).Approximately 1048 (0.31 %) non-immune patients will have been exposed to asero-positive unit based on the 1990 prevalence study by Dr D G Woodfield,Director of the Auckland Blood Transfusion Service. Of these approximately 733(70%) will contract the Hepatitis C virus. Clinical acute Hepatitis C will developwithin six to twenty-six weeks in approximately 183 (25%) patients and asnallnumber. 4.0l %) will develop fulminant Hepatitis C which will lead to death orliver transplant.
Of the 733 infected patients 323 (43.9%) will survive, the remaining 410 patientshaving died from other causes within two years. 160 patients will have no adverseconsequences of the infection, while 163 will develop some liver disease. Of these130 will have chronic low-grade disease (approximately half will have no adverseeffects while the other half will have minimal disruption to daily living.) A total of
INQUIRY REPORT 7
33 patients will develop aggressive liver disease with cirrhosis and some maydevelop hepatocellular cancer an average of 15 years post transfusion
There are several estimates of the total number of haemophiliacs in New Zealandwith the highest estimate being 535 Factor VIII and 95 Factor IX haemophiliacs.Of these, approximately 38% are severe, with a factor level of less than or equal to5% of normal, thus having a greater use of blood products.
A study conducted in 1990 revealed that 70% of haemophiliacs were HCV positive.That is, infection took place for 70% of the at risk population before any screeningtests were available.
It is more difficult to quantify the numbers of haemophilia patients recently exposedas pasteurisation to 60°C of pooled plasma products is effective in reducing the totalnumber of infected batches as indicated by the Karolinska article (in Appendix IIILancet 1992: 340: 305-306). If pasteurisation was not effective at all, then onecould expect that of the estimated 50 patients who have Factor IX deficiency andrequire concentrates on a moderately regular basis, an estimated total of 15 wouldnot have been infected in 1990. Of these 15, 11 are at risk of developing HepatitisC infection through receiving pooled plasma concentrates. A total of 5 patientswould be predicted to develop chronic active hepatitis if there were no deaths fromother causes and 2 would go onto developing cirrhosis and possibly hepatocellularcarcinoma.
5Blood Transfusion Services In New Zealand
5.1Organisation of Services
The New Zealand Blood Transfusion Service (BTS), as currently organised, dealswith the recruitment of blood donors, the collection of blood (based on voluntarydonations), the screening and accreditation' of donated blood (eg HIV, Hepatitis B& C), the processing of donated blood into a variety of components, and the storageand dispensing of blood and blood products as requested by clinicians. Plasmaseparated from donated blood is frozen and pooled prior to dispatch to a centrewhere it is fractionated 2 into specific components.
Organisationally the New Zealand blood transfusion services tend to be part of AreaHealth Board pathology services, they comprise:
blood banks in most large hospitals (these store, dispense and provide cross-matching services);
18 sub-regional centres (mainly for blood collection, some testing);
'Accreditation: The process of testing blood and plasma donations for bloodgroups, relevant red cell antibodies and evidence of certain infections, and the finalcceptance and labelling of the blood/plasma for clinical use
'-Fractionated blood products: Therapeutic blood products prepared from plasmaby an integrated series of physico-chemical separation steps. Through letters ofagreement with New Zealand, this process is undertaken at the CommonwealthSerum Laboratories (CSL), Victoria, Australia.
INQUIRY REPORT 8
six regional centres (provide full range of services, support sub regions andhandle local distribution of Australian Commonwealth Serum Laboratories(CSL) products);
some additional services provided by the Auckland regional centre (liaisonwith CSL, storage and distribution of CSL products, some purchasing).
The Area Health Boards in which the six regional blood transfusion centres arebased bear the major costs of supplying blood products to the users - ie. otherboards and the private sector. Operating costs of the regional blood transfusioncentres (including the supply of fractionated products by CSL from plasmaproduced in New Zealand) are estimated at around $20 million (direct costs).
There is currently only limited formal co-ordination of the BTS at a national level -each regional centre is operated largely independently. There is a large degree ofvoluntary co-operation between regions.
No charges may be made for blood and blood products (Part III A of the Health Act1956).
There is no national database of donors. Each of the regional centres has anindependent system for donor management.
In 1991, 167,6988 units of blood were donated in New Zealand. The six regionalcentres collected close to 30% of this blood at their donor centres, and 50% frommobile collections. Just over 20% of the blood was collected from the smallercentres.
Average level of donations per 1000 population varies from a low of 46 inWellington to a high of 55 in Auckland.
More blood is collected than is required for whole blood and red cell usage becauseof the high demand for plasma derived products. Over 90% af all blood collectedhas the plasma retrieved for processing. In recent years the total blood requirementin New Zealand has declined due to increased efficiency in the use and processingof blood products.
New Zealand is almost wholly dependent upon the CSL for the processing andsupply of fractionated blood products. Frozen plasma is sent by the individualregional centres to the CSL in Melbourne for fractionation into various proteinconstituent products. The Auckland centre has a limited fractionation capability.which manufactured 4% of New Zealand's requirements for Factor VIII in1991/92.
There are currently 6 medical specialists qualified in transfusion medicine in theNew Zealand Blood Transfusion Service, equating to 4.5 full time equivalents.
It is understood that reviews of the Blood Transfusion Services, 1987 and 1989, hadconsidered the possibility of establishing a national agency but that this had not beensupported.
5.2 New Zealand Links with Commonwealth Serum Laboratories (CSL)
Since 1962, CSL in Melbourne has received plasma from New Zealand forprocessing into fractionated products. All plasma from New Zealand is sent by air,
INQUIRY REPORT
directly to Melbourne from one of the three international airports in New Zealand.All finished products are air-freighted to Auckland for distribution. Approximately30,000 litres were forwarded in the last year.
In 1987, New Zealand's arrangement with CSL was formalised by exchange ofletters between the Director-General of Health and the Managing Director, CSL.The letters followed a review in New Zealand on the feasibility of establishing afull-scale fractionation plant in New Zealand. The then Minister of Health haddecided against such a development in New Zealand on the grounds that it would bemore economical to continue with the system of having CSL produce bloodproducts from New Zealand plasma.
The Director-General's letter states "We agree also that it would be most desirableto establish an explicit and on-going commitment for the use of your facilities by anexchange of letters of intent and understanding rather than a formal contract".
Initially, this arrangement maximised the benefits for both countries because bloodfrom both New Zealand and Australia was pooled for fractionation processes.Following the HIV/AIDS risks in the early 1980s, the two blood streams wereseparated because HIV infection in New Zealand was significantly lower than inAustralia. While increasing the safety of New Zealand fractionated products, thedecision reduced the efficiencies in the arrangement.
This agreement involves about $6.2m per year.
5.3 Blood Transfusion Advisory Committee
The Blood Transfusion Advisory Committee (BTAC) was established in 1963 undersection 13 of the Hospitals Act 1957 to advise the Minister of Health on "technicalaspects of blood transfusion". The medical directors of the six regional bloodtransfusion centres (Auckland, Hamilton, Palmerston North, Wellington,Christchurch and Dunedin) make up the Committee. In the 1970's and early 80'sthe Chairman was a medical officer from the Department of Health. Subsequently,up to December 1990 there was an independent Chairman. The Committee isserviced by the Department of Health.
The BTAC has itself established three subcommittees:
A Technical Working Party which advises BTAC on technical issues.Membership comprises charge technologists from each of the six regionalcentres.
A Histocompatability Working Party which advises BTAC on tissue typingissues. Membership comprises a separate team of charge technologists fromfive of the six regional centres.
A Donor Managers Working Party which advises BTAC on donorrecruitment issues. Membership comprises the Donor Managers from sevencentres.
INQUIRY REPORT 10
6Summary of Chronological Events in relation to Hepatitis C
7/8 December 1989 BTAC minutes noted that tests have become available forHepatitis C and that testing is likely to start in Australia in afew months. It was stated that the Department of Healthshould fund tests to determine the frequency of Hepatitis Cin New Zealanders as a prelude to full-scale testing.
19 February 1990HCV screening was introduced throughout Australia.
22/23 February 1990 The BTAC noted at its meeting that Australia had startedtesting for Hepatitis C (HCV) and reported that AbbottIndustries had donated testing kits to conduct a trial in NewZealand to determine the positive rate for Hepatitis C inblood donors. BTAC also noted the Australianrecommendation that all new haemophiliacs should be givensuper heat-treated Factor VIII. This was recorded in FLAG(Red Cross Fractions Liaison Advisory Group) minutes "itwas believed that in the interests of responsibly providingthe safest possible service, the (Red Cross) Society shouldendeavour to ensure that all newly diagnosed haemophiliacsor those not previously exposed to treatment withconcentrate should be given high purity AHF concentrate iftreatment with concentrate is required". BTAC noted that"While high purity Factor VIII is not in New Zealand yet,all Factor VIII used in New Zealand will eventually be ofthis type. Current UK experience suggests that since theintroduction of the Elstree method, there have been nobreak-through cases of HIV or Hepatitis C in patientstreated with this concentrate."
March 1990The Minister of Health, Rt Hon Helen Clark, was advisedthat a trial was being conducted.
April 1990 Associate Professor C. Tasman-Jones, Department ofGastroenterology, School of Medicine, Auckland forwardeda paper supporting the case for blood screening for HepatitisC to the Director-General of Health.
30 April 1990 Medical Director, Auckland RBTS visited CSL andreported to BTAC, "80°C heated material has beenprocessed and the protocol for trial of this is in preparation.We can be involved in the evaluation if we wish. It hasbeen used successfully in the UK and some is being used inthe USA."
INQUIRY REPORT II
May 1990 New Zealand Communicable Diseases Centre was asked bythe Department to do a cost benefit analysis and commenton the technical aspects of testing. This was submitted tothe Communicable Disease Control Advisory Committee(CDCAC).
4 June 1990 The New Zealand trial of Abbott first generation test kitswas completed. The trial in 1990 indicated that HCVantibody was likely to be present in the blood of 0.47% ofdonors (taking false positives into account thisis likely tofall to approximately 0.31%). The current test to detectHCV antibody in blood did not identify all carriers ofHepatitis C. It would allow identification of approximately86% of infected donors and the elimination of their bloodfrom the blood supply. Second generation tests, withgreater specificity, were expected to be available in the late1990 year.
13 June 1990 Dr E W Berry, Chairman, Medical Advisory Panel, NZHaemophilia Society, wrote to the Chairperson, BTACsuggesting that the following matters be considered at the14/15 June 1990 meeting of BTAC. She advised that thepanel had recommended that super heat (80°C) treatedconcentrates are considered to be a minimum standard offactor concentrate which should be available for thetreatment of Haemophilia A and B (absence of Factor VIIIand Factor IX). Further recommendations were that allblood donors be tested for HCV and that a representative ofthe Haemophilia Society become a member of BTAC.
14115 June 1990 The BTAC minutes record that the letter was tabled, anddiscussion centred only on the membership of BTAC.BTAC recommended at its meeting the introduction of HCVscreening. The minutes also noted that Dr S Martindale,Advisor (Science), Therapeutics Section, Department ofHealth, advised BTAC that super-heat treated Factor VIII isa medicine requiring Ministerial consent before it can belegally used and distributed in New Zealand.
27 June 1990 The NZCDC report was submitted to the CDCAC, advising"that the CDCAC recommend to the Minister of Health theimmediate funding of a nationwide screening programme ofblood for tranfusion for Hepatitis C antibodies".
29 June 1990 The BTAC Chairpcson, Mr G K Chapman, wrote to theDepartment of Health about the BTAC recommendation,urging the immediate introduction of screening and setting
INQUIRY REPORT 12
out reasons for doing this and the consequences of notproceeding.
11 July 1990
An internal departmental request for advice from theDepartmental Legal Services Section resulted in advice that
12 July 1990 The CDCAC considered a paper by Professor C Tasman-Jones on Hepatitis C, at the request of the Minister ofHealth. They also tabled a paper by Dr N Wilson,NZCDC, "Cost-effectiveness of screening for HCVantibodies in blood for transfusion".
CDCAC agreed that advice to the Minister should be asfollows:
"Mandatory testing for the presence of HCV antibody houldbe introduced for all blood and blood products fortransfusion.
On scientific grounds it is difficult to disagree with ProfessorTasman-Jones' other four conclusions:
-Surveys should be made to show the relative incidenceof Hepatitis C in selected populations.
-Interferon should be made available for treatment ofHepatitis C in controlled clinical research units.
-The relative importance of Hepatitis C in chronic liverdisease should be ascertained by appropriate research.
-A national policy on liver transplantation should bedeveloped."
- 27 July 1990 A letter from Abbott Diagnostics to the Minister of Health,noted "they understand a decision has been made to screenall donors for HCV".
12 August 1990 Dr Stewart Reid, Chairman of CDCAC, wrote to theMinister of Health advising that the committee wasunanimous in its agreement that mandatory testing for HCVshould be introduced. This was one of a number of issuesraised with the Minister of Health. (NB. Normal procedurein processing Ministerial correspondence involves theimmediate referral of letters by a clerk in the Office of theMinister to the Department of Health for the preparation ofa draft reply. A period of one month is normally allowedunless an urgent reply is requested.)
INQUIRY REPORT 13
26 August 1990 The Minister of Health noted the CDCAC'srecommendation and requested a full briefing from theDepartment. The Inquiry found no record of that briefingbeing given.
28 August 1990 The Minister of Health replied to Abbott Diagnostics,stating "I understand that at a meeting in July the CDCACconsidered a recommendation that blood be screened forHepatitis C but I have not yet been advised of anyrecommendations arising from this meeting".
28 September 1990 An issues paper from the Manager, Health Services Policywas tabled by the Department of Health CorporateManagement Group. It considered legal and cost-effectiveness issues relating to Hepatitis C screening. 'Thereis no record of any resolutions made on the issues raised inthis paper.
September 1990 The Medical Director, Auckland RBTS reported on hisattendance at the Australian Red Cross Blood TransfusionServices executive committee held on 19/20 September1990 and the National Blood Transfusion Meeting, 20September 1990. His report noted that three batches ofProthrombinex heated at 80°C had been prepared and wereawaiting clinical evaluation.
24 October 1990 The Minister of Health replied to the Chairman CDCAC,thanking the committee for considering issues in relation toHepatitis C and these would be "followed up by theDepartment".
27 October 1990General election and change of Government.
2 November 1990New Government took Office. Hon. Simon Upton wassworn in as Minister of Health.
There is no reference in the Department of Health's BriefingPapers to the incoming Government to the issue of HepatitisC.
29/30 NovemberThe BTAC meeting minutes noted:1990
"Members concern over their legal position regarding thenon-introduction to date of Anti-HCV testing as previouslyrecommended by the BTAC and CDCAC.Dr Faed notified the meeting that he intended writing to theGeneral Manager Otago Area Health Board advising thatdue to the continuing delay in introducing Anti-HCV testing
INQUIRY REPORT 14
of the blood supply, he was no longer prepared to acceptresponsibility for patient safety. Regional Directorsconcurred with this action.Jill Stringer advised that people contracting Hepatitis Cfrom contaminated blood would be eligible to apply forACC benefits."
BTAC agreed to write to the Director-General requesting:
"(a) response to the recommendations on Anti-HCV testingcontained in a letter from the BTAC dated 29 June 1990.Clarification of Regional Directors legal position if patientscontract Hepatitis C from the blood supply was sought also.Include statement advising that CSL are currently refusingto accept blood that has tested HCV positive.
(b) In addition a letter should go to the Director-Generalrecommending that "the New Zealand CommunicableDisease Centre establish confirmatory testing proceduresfor HCV positive specimens, plus an external qualityassurance system for all laboratories involved in HCV Abtesting".
(c) Members agreed that after confirmatory testing, HCVpositive donors should be retired from the donor panel andreferred for appropriate medical investigation andcounselling."
1 December 1990 Resignation of BTAC Chairperson, Mr Chapman took effect.
5 December 1990 The New Zealand Medical Association (NZMA) Assemblyrecommended that funds should be made available byGovernment for mandatory screening.
12 December 1990 The NZMA wrote to the Minister of Health, advising of thisrecommendation.
21 December 1990 Secretary, BTAC wrote to the Director-General of Healthreminding him of the June recommendation from BTAC thatscreening of blood donations for Hepatitis C be introduced,and noted BTAC's concern about the need for an urgentdecision.
19 March 1991 The Medical Director, Auckland RBTS reported to BTAC onhis annual visit to CSL. He noted that "High heat treatmentfor Prothrombinex is not yet finalised, partly due to the needto add ATIII to the product for stability purposes. No datehas yet been set for its availablility". A new product, mono
INQUIRY REPORT 15
component Factor IX concentrate, "Haemostat IX", is to beprepared. No dates have been set for its release.
20 March 1991 The General Manager Services, Department of Healthattended a South Pacific Commission Regional Heads ofHealth Services Conference in Noumea on 11-15 March 1991,and reported that Dr Gary Schatz from the CommunicableDisease Centre, Atlanta spoke on Hepatitis C and hadindicated the screening tests then available had a high falsepositive rate. Dr Schatz is reported to have commented "thatanyone under pressure to use the current generation of kitsshould wait for the next generation products which should beavailable in 6-12 months". He also recommended Dr MiriamAlter for expert comment.
8 April 1991 3 April paper from Manager, Health Services Policy toCorporate Management Group, proposed that "screening forHCV be introduced and asked CMG to note that there are anumber of issues to be resolved."CMG agreed that a paper should be prepared for theMinister, recommending that screening be introduced, afterthe issues of test specificity and funding had been investigatedby Policy Group.
11 -12 April 1991Mr John Dagger of the Haemophilia Society, attended theBTAC meeting. The minutes noted:
"BTAC members responded to the specific concerns of theHaemophilia Society as follows:
Hepatitis C testing of blood donations.
• currently no guarantee can be given that donated bloodwill be screened before transfusion to haemophiliacs.
• the Standards for the BTS being prepared by the BTACcontain an obligatory requirement to screen donated bloodfor Hepatitis C.
• the availability of a new and more specific test for theHepatitis C virus is anticipated for the very near future.
• the option exists for the Haemophilia Society to lobby theMinister direct on the issue of introducing Hepatitis Cscreening of the blood supply."
Other issues discussed included:
INQUIRY REPORT 16
• present supply of Coagulation Products, and the phasingout of the use of Cryoprecipitate.
• national supply of Coagulation Products under AreaHealth Boards.
future availability and use of Recombinant Factor VIII.
The minutes also noted:
"Anti-HCV Testing: Confirmatory Testing
Dr Woodfield (Medical Director, Auckland RBTS) reportedreceiving written advice from Dr Martin Tobias, ManagerNZCommunicable Disease Centre, that Anti-HCV confirmatorytesting is now available at the Centre."
19 April 1991 The Morbidity and Mortality Weekly Report from CDC,Atlanta published "Public Health Service InteragencyGuidelines for Screening Donors of Blood, Plasma, Organs,Tissue and Semen for Evidence of Hepatitis B and HepatitisC". These guidelines recommended that all donations ofwhole blood and components for transfusion be tested foranti-HCV by EIA (enzyme immuno assay).
7 May 1991 CSL wrote to the Director-General of Health, advising thatAustralia had introduced screening for HCV in February1990. The letter noted the importance of eliminating HCVfrom the starting plasma. CSL requested comments andadvice on when New Zealand would be in a position tointroduce screening.
15 May 1991 The Department advised the Minister of Health of its supportof the CDCAC recommendation and that any final decisionshould be deferred until the specificity of the then availabletest had been investigated and further work on cost estimatesand on blood transfusion services funding had beencompleted.
20 May 1991Minister of Health approved the recommendation that
"You note:
1. that the Department supports the CDCACrecommendation that screening of donated blood forHepatitis C antibody should be introduced;
INQUIRY REPORT 17
2. that the Department considers the final decisionon fundingshould be deferred until the specificityof the currentlyavailabletesthasbeeninvestigated and further work on costestimatesand on blood transfusion services has been completed;
3. that a paper will be prepared for you on futureoptions for blood transfusion services by 30 June1991."
30 May 1991 A letter from Dr H W H Pullon on Manawatu Regional BloodTransfusion Services letterhead and signed as ConsultantHaematologist and Regional Transfusion Director to theAssociate Minister of Health, Hon Katherine O'Regan,reiterated the advice of BTAC that HCV screening shouldcommence forthwith, and offered BTAC's assistance to advisein any way possible to clarify any doubts or concerns whichpoliticians may have as regards this matter.
June 1991 Abbott second generation test kits were released for marketingin New Zealand. Limited screening of blood began on theinitiative of some Regional Blood Transfusion Centres (eg,Otago).
June 1991The Department of Health requested information fromNZCDC about technical developments in testing.
13 June 1991 NZCDC advised on improved performance characteristics ofthe second generation screening test, as well as developmentsin confirmatory and supplemental testing. The availability ofsecond generation tests in New Zealand was also mentioned.
17 June 1991 Letter from Mr M R Mapperson, President, New ZealandHaemophilia Society to the Minister of Health re-emphasisedthe need for testing of blood donors.
1 July 1991 Hon Katherine ORegan replied to Dr Pullon, advising thatthere was no need for BTAC to meet with Ministers on thisissue and pointing out that the proposal for Hepatitis C testinghas to be considered fully in the context of other pressingpriorities for funding.
10 July 1991 Dr E Berry wrote to the Minister of Health, copying the letterto the Acting Director-General of Health, expressing theconcern of the Medical Advisory Panel of the New ZealandHaemophilia Society about the supply and funding ofspecialised factor concentrates for patients with bleedingdisorders. Dr Berry noted the complete lack of budgetary
INQUIRY REPORT 18
provisions and commented that the prospect of a viral freeproduct is extremely desirable.
The Department referred this letter to BTAC. (it wasconsidered at the 28129 November 1991 meeting of BTAC.)
25 July 1991 Dr H W H Pullon of the Manawatu Regional BloodTransfusion Service wrote to the Minister of Health on behalfof all Regional Transfusion Directors advising that they "areappalled and dismayed that there has still been no decision onthe funding of Hepatitis C testing of blood donations withinNew Zealand. We now regard this as an extremely urgentmatter, and of great public concern."(NB - an extract from a two page letter.)
30 July 1991
The Department of Health prepared a comprehensive briefingto the Minister recommending that he:
1. agree in principle to the provision of centralfunding for the introduction of Hepatitis C screening;
2. note that the maximum cost in a full financialyear would be $2 million, but that it is expected thatthis cost could be reduced;
3. instruct the Blood Transfusion AdvisoryCommittee to meet as soon as possible to providethe Minister with options for the introduction ofscreening.
The Minister of Health approved this on the same day.
31 July 1991The Minister of Health replied to Dr H Pullon:
"I appreciate that this is a matter which is of considerableconcern for those involved with blood transfusion services andthat from your perspective action on the introduction ofHepatitis C screening has been slow. I have a responsibility,however, to carefully consider the implications and relativepriority of all proposals which call on the limited healthdollar.
I am now able to advise you that I am prepared to support inprinciple the provision of central funding for Hepatitis Cscreening.
I am concerned, however, at the high cost of the screeningprogramme, and wish to see the cost estimate of $2 million
INQUIRY REPORT 19
per annum reduced if at all possible. This may require sometrade-off in terms of what is optimal. I am advised that theBlood Transfusion Advisory Committee is best placed toprovide expert advice on this issue.
I am therefore instructing the Department of Health to arrangea meeting of this committee as soon as possible, in order toprovide me with options for the introduction of a screeningprogramme."
August 1991 A letter was received by the Minister of Health enclosing anundated newsbrief of the New Zealand Haemophilia Societywhich explained the nature of Hepatitis C. It contained asection on the safety of blood products which stated:"Some blood from New Zealand donors is pooled and sent toCSL in Australia for processing into Factor VIII and FactorIX concentrates. This Factor VIII is heat treated to 80°Cwhich seems to eliminiate the Hepatitis C and HIV virus.Factor IX concentrate (Prothrombinex PTX) is heat treated to60°C which inactivates HIV, but not the Hepatitis virus.Some blood from New Zealand donors is processed in NewZealand and made into Factor VIII concentrates. This FactorVIII is heat treated to 60°C which inactivates only the HIVvirus. Future productions later this year will probably beheated to 80°C, inactivating the Hepatitis C virus also."
5 August 1991 Letter from Dr H Pullon to the Minister of Health - onManawatu Blood Transfusion Service letterhead and signed asRegional Transfusion Director - clearly writing on behalf ofthe Medical Directors, as members of the NationalTransfusion Advisory Committee "We are uncertain as towhich Health Department officials are involved in overseeingtransfusion matters, and indeed organising TransfusionAdvisory Committee meetings". He suggested a date for aBTAC meeting to consider options for screening andrequested the presence of senior Health Department officialsat the meeting.
8 August 1991 Hon. M Williamson, on behalf of the Minister of Health,replied to Mr Mapperson, "I am pleased to advise you that Ihave now approved the provision of central funding forHepatitis C screening. The Blood Transfusion AdvisoryCommittee is to meet in the near future to provide me withoptions for the implementation of the screening programme."
8 August 1991 Hon. Simon Upton, replying to a letter dated 11 July 1991from Dr Berry about testing for Hepatitis C, stated "I ampleased to advise you that I have now approved the provision
INQUIRY REPORT 20
of central funding for Hepatitis C screening. The BloodTransfusion Advisory Committee is to meet in the near futureto provide me with options for the implementation of thescreening programme."
24 August 1991 Hon. Simon Upton, replied to Dr. Pullon's letter of 5 August1991 with suggested meeting date and stating that the Personaland Public Health Section of the Department's Policy Groupwill be involved in overseeing blood transfusion servicesmatters.
5 September 1991 BTAC members and departmental representatives met todevelop HCV screening costing options.
1 October 1991 The Medical Director, Auckland RBTS reported on hisattendance at the Australian Red Cross Blood TransfusionServices executive sub-committee held on 30 September 1991.His report noted that "an application for high heat treatedPTX is being prepared for submission to the AustralianTherapeutic Goods Administration. VFX H-T (800) will besupplied in February 1992, if all goes well. It is available onIPU (that is, named patient use). *We need to use up ourProthrombinex before high HT material becomes available.(The report uses *s and underlining to indicate mattersrelevant to New Zealand.)
2 October 1991 The Medical Director, Auckland RBTS reported on his 2October visit to CSL, noting that CSL is to advise the NewZealand Department of Health of the trends in overseasfractionation units of not accepting HCV antibody plasma andthat CSL will soon be requiring this as a standard criterion foracceptance of plasma for fractionation.
28/29 November 1991 The BTAC meeting minutes noted that:
"Anti-HCV Testing: Confirmatory Testing
Confirmatory testing for anti-HCV was not being done at theNew Zealand Communicable Diseases Centre yet."
and
Hepatitis C testing
Russell Ritchie reported that the paper on funding options forHepatitis C screening was shortly (following week) to go tothe Minister. A decision should be made shortly. Directorsreiterated their concerns over the delay of introducing
INQUIRY REPORT 21
screening and the ethical problems associated with issuinguntested blood.
Concern was also expressed over the implication of the newACC Bill (Accident Compensation and RehabilitationInsurance Bill) and Directors were encouraged to look overthe proposed legislation and make submissions.
ACTION REQUIRED: Secretary to find out the closing dateof submissions and inform Directors.
Supply and funding of specialised factor concentrates forpatients with bleeding disorders
The issue referred to BTAC by the Department was raised ina Dr Elizabeth Berry letter on behalf of the NZ HaemophiliacSociety. Also raised in a previous BTAC meeting, the issuewas whether the Department of Health or the BloodTransfusion Services directly supplied factor concentrates forthe treatment of haemophiliacs. It was generally agreed thatalthough specialised factor concentrates were a non-humanproduct and there was no specific budget for its procurement,channelling it through BTS was preferred, as the Serviceswere part of the overall treatment of haemophiliacs. BTScould also act as a control mechanism against unnecessaryusage". (This letter was replied to on 2 April 1992.)
29 November 1991 A briefing paper prepared by the Department for the Minister,setting out three fully costed options for HCV screening ofdonated blood, recommended that the Minister:
1. agree that option 1 be implemented i.e alldonated blood should be screened for HCV at anestimated cost of $1.642million in 1992/93 and$1,590,200 in. succeeding years.
2. note that the preferred second option is option2, ie to test all donors once annually at an estimatedcost of $1.534 million in year 1, $1,340,885 insubsequent years.
3. note that option 3 is least safe and the leastpreferred option: to test 50 % of all donations at a costof $1.733 millon in a year 1 and $1,293 million insubsequent years.
4. agree that the Auckland Area Health Boardshould manage the letting of the tender for HCV test
INQUIRY REPORT 22
kits, payment for the on-going supply of test kits andthe national donor information supplies.
5. agree that HCV screening of blood should beundertaken only by the six regional laboratories whichcurrently undertake HIV screening.
5 December 1991 The Minister of Health agreed with option 1, "subject to the1992/93 budget round" (an annotation in his own hand-writing), ie screening of all donated blood for HCV at anestimated cost of $1.642 million in 1992/93 and $1,590,200in succeeding years. He also noted recommendations 2-3 andagreed to recommendations 4-5 above. The Minister directedthe Department to address the issue of funding.
7 February 1992 Dr H W H Pullon, Regional Director, Palmerston North BTSwrote to the Director-General of Health on behalf of all of theMedical Directors urging urgent action to introduce HCVscreening.
"We ask that this matter be expedited and that the fundingarrangements for Hepatitis C antibody screening be finalisednow. We continue to endorse the previous recommendationthat all blood donations collected within New Zealand betested for Hepatitis C antibodies.
As you are aware, the Transfusion Advisory Committee willbe meeting in mid March 1992, and we hope that a finaldecision about funding for Hepatitis C antibody testing willhave been made by that time. If testing is to be commencedat the beginning of the next financial year it will be necessaryfor the Hepatitis C antibody test tender to be put out in lateMarch/early April 1992. It should then be possible toperform test kit evaluation and make a decision on which testkit is to be used during May 1992. Any delay in the timetableoutlined will further delay introduction of testing beyond thestart of the next financial year."(NB - Extract from a two page letter.)
27 February 1992 A briefing paper was provided to the Director-General on theissues raised in Dr Pullon's correspondence and a responsewas attached for his snature, outlining that the Minister hadalready received the Department of Health paper (29/11/91)and that the Minister was expecting to announce a decisionsoon.
INQUIRY REPORT 23
10 March 1992The Minister announced that he was seeking funding in the92/93 Budget for the HCV screening programme.
19/20 March 1992 The BTAC meeting minutes noted that:
"HEPATITIS C
Sheryl Small reported that the Minister of Health is seekingGovernment approval for funding in the 1992/93 Budgetround. The issue is now awaiting Government approval.
There was concern over the lag-time between fundingapproval and implementation. Dr Gibbons suggested that thetendering process start in anticipation of Governmentapproval. The BTAC selected Drs Gibbons and Woodfield asits representatives on the Committee involved with thetendering and evaluation of the test kits.
A press release from the Minister of Health stated that thescreening programme would be conducted by the six RegionalBlood Transfusion Centres. It was suggested that this beclarified: screening would be made in each region under thedirection of the regional director.
ACTION REQUIRED: Secretary to draft a letter to theDepartment of Health recommending that in view of the timerequired for the evaluation of test kits that a tender beestablished for Hepatitis C testing."
25/26 March 1992 NZCDC held a Hepatitis C workshop and the Minister wasinvited to open it and announce the Government's decision refunding for the HCV screening. The Minister declined theinvitation.
27 March 1992 Medical Director, Auckland RBTS reported on his visit toCSL, noting that "application for registration by the TGA isexpected by mid-April 1992, but that PTX H-T (80°C) couldbe released immediately under Section 29, Medicines Act1981 (for a period up to two years) and that a section 23application could be lodged".
March/April/May A series of letters was exchanged between Dr Berry, the1992 Auckland RBTS, the Auckland Area Health Board, the
Department of Health and the CSL about the process formaking individual named patient applications and obtainingPTX H-T. The reasons that this exchange of letters did notresult in the availability of any of these products relate to thecomplexities of legislative provisions and administrative
INQUERY REPORT 24
procedures associated with the use of unlicensed products bothin Australia and New Zealand.
2 April 1992 The Secretary, BTAC replied to Dr Berry's letter of 10 July1991, stating "The BTAC appreciates your concerns andacknowledges the special circumstances of haemophiliacs. Itnoted, however, that there was no specific budget for theprocurement of specialised factor concentrates.
As you would be aware, Area Health Boards currently fundthe blood transfusion services from the population based grantboards receive from the Department of Health. Thisallocation is determined having regard to competing claims ofother services on a boards resources. The funding the bloodtransfusion services receive is not tagged for any particularactivity within the scope of the services they provide. TheBTAC noted your suggestion and agreed that the bloodtransfusion services are better placed for channellingspecialised factor concentrates, providing funding was madeavailable."
22 April 1992 The Medical Director, Auckland RBTS wrote to CSLrequesting unregistered 80°C P1'X H-T on behalf of threeHepatitis C antibody negative patients. He stated " It seemsthat it must be near the time when we should make a batch ofNew Zealand plasma into the high heat treated material.What is the possibility of this and will it be possible to releasesome Australian sourced high heat treated Prothrombinex forour use in at least (named patient)?"
6 May 1992 A fax was sent from CSL to the Medical Director, AucklandRBTS, stating that he would have to ask the New ZealandDepartment of Health whether they are prepared to issue anIPU approval for the product which has not yet beenregistered by the Australian TGA. CSL also indicated theywould consider the feasibility of making a batch of PTX H-Tfrom New Zeland plasma. They noted they would first needto make some antithrombin (AT III).
7 May 1992 A letter to Dr G R Boyd, Manager, Therapeutics, Departmentof Health from Dr Woodfield asked for advice on how toproceed with a request from Dr Berry to importProthrombinex HT fro- CSL for some of her young patientsnot yet exposed to Hepatitis C.
8 May 1992The Officials Committee on Expenditure Control considered arequest by the Minister of Health for new funding for
INQUIRY REPORT 25
Hepatitis C testing, and recommended to Cabinet, onTreasury advice, that approval only be given if funded fromreprioritisation within Vote: Health. Treasury had argued thatfunding should come from existing AHB operating grants asBoards are the major beneficiaries of reduced health care costsdue to screening. Cabinet minutes (CAB (92) M20/13k)subsequently record that Cabinet agreed that the costs ofHepatitis C testing of $1.847m in 1992/93.. .be absorbed inthe existing Area Health Board grants.
14 May 1992 BTAC wrote to the Director-General urging that the test kittendering process be commenced in anticipation of fundingbeing approved.
25 May 1992 In a letter from Dr Boyd to Mr D King, General Manager,Auckland Area Health Board, in reply to the letter of 7 May1992 from the Medical Director, Auckland RBTS, Dr Boydadvised Mr King of the sections of the Medicines Act 1981(Sn 29 and Sn 25) under which which Prothrombinex - HTcould be legally used. This letter was copied to the MedicalDirector, Auckland RBTS.
12 June 1992 The Medical Director, Auckland RBTS wrote to CSL statingthat PTX H-T could be legally used in New Zealand. Hewas unsure "what IPU approval is", as he did not recall everhaving to use it in relation to other new products produced byCSL. He suggested that if there was a problem, CSL shouldcontact the New Zealand Department of Health.
He also commented "We will be very glad when you make abatch of PTX H-T for us. It will be very welcome."
19 June 1992 The Department prepared a briefing paper to the Ministerseeking approval for the Department's plan forimplementation of the Hepatitis C (HCV) screeningprogramme. The Department view was that screening shouldbe administered nationally and provided by Regional BloodTransfusion Centres as was the case with HIV testing.
The paper recommended that the Minister:
1. note the rationale for the Department's plan.
2. reconfirm that funding will come from the AreaHealth Board POBOC as approved by Cabinet (92) M20/13k.
INQUIRY REPORT 26
3.approve that testing will be carried out by thesix Regional Blood Transfusion Centres.
(The Minister's response to the briefing paper has notbeen located.)
June 1992National tender for second generation test kits was let.
9/10 July 1992 The Department consulted the BTAC on the tenders. Adecision was made on the successful tender. (NB - The draftminutes of the BTAC meeting became available on 15December 1992.)
27 July 1992HCV screening commenced nationally and the fol1oiinginitiatives were undertaken by the Department:
(i) press release prepared(ii) HCV educational materials produced (disseminated in
September1992)(iii) kits provided to all BTS(iv) NZCDC contracted to provide confirmatory testing(v) circular letter to medical practitioners prepared
announcing Hepatitis C screening.
Funding for the purchase of test kits was met from AreaHealth Board base allocations.
31 July 1992 Dr Berry wrote to the Minister of Health stating that "the onlyFactor IX concentrate available in New Zealand is heat treatedto only 60°C which inactivates HIV but not Hepatitis virusesand is thus able to continue infecting new patients.
Supplies of 80°C heat treated Prothrombinex from CSL havestill not eventuated and haemophiliacs with Factor IXdeficiency and others requiring this product are faced with thedilemma of leaving haemorrhages untreated or riskingHepatitis C infection. Commercial Factor IX products whichdo not transmit Hepatitis viruses are now available but areexpensive, and no budgets have been developed in theTransfusion Service to buy such products."
Dr Berry concluded by saying "The main purpose of thisletter is to request the necessary funding to purchase suppliesof safe Factor IX concentrate until such time as appropriatelocal products come on stream".
(NB. Normal procedure in processing Ministerialcorrespondence involves the immediate referral of letters bya clerk in the Office of the Minister to the Department of
INQUIRY REPORT 27
Health for the preparation of a draft reply. A period of onemonth is normally allowed unless an urgent reply isrequested. Hon Simon Upton replied on 4 September.)
6 August 1992 The Medical Director, Auckland RBTS wrote to CSL askingwhether CSL performs HCV testing on Prothrombinex. Heindicated that he had done HCV testing and found them to benegative.
21 August 1992 Secretary BTAC wrote to Dr R Fong, Director, WellingtonRBTC, stating "Following your inquiry, I consulted ToddKrieble about the issue of retrospective testing of blood forHepatitis C.
Todd said that the the issue of retrospective testing of bloodalready in stock was discussed at the meeting where DrWoodfield mentioned Auckland's intention to carry this out.It was budgeted for and there is a Ministerial expectation thatblood in stock will be tested.
Call me if you wish to discuss this."
(NB Mr Todd Krieble was Board Liaison Manager, AreaHealth Board Contracts, Department of health)
21 August 1992 CSL replied to the Medical Director, Auckland RBTSoutlining that tests on present PTX stocks would be a waste oftime because HCV antibodies are proteins, and the plasmapooling process for producing PTX diluted the protein contentto such an extent that screening tests would be unable todetect the presence of immune globulin protein.
4 September 1992 The Minister of Health replied to Dr Berry, noting that bloodtransfusion services are currently funded through Area HealthBoard bulk grants. In addition, he noted "the Department ofHealth makes an annual grant to the Auckland Area HealthBoard for purchasing, on behalf of the country, fractionatedproducts from CSL in Australia. Apart from that specificallocation, the funding that blood transfusion services receiveis not tagged for any particular activity. The bloodtransfusion services, through the Area Health Boards, havethe responsibility to provide services that meet the healthneeds of people in their regions. I understand the distributionand the monitoring of usage of Factor VIII and other productsfor the treatment of haemophiliacs is already handled throughthe six regional blood transfusion centres. I consider that
INQUIRY REPORT 28
your organisation should discuss any issue related to thetreatment of people with bleeding disorders with the regionaldirectors of the blood transfusion services. I will also referyour letter to the Blood Transfusion Advisory Committee forcomment."
October 1992 The Secretariat of the PTAC wrote to Professor V SChadwick, President of Society of Gastroenterology listingthe current approved indications of Interferon and asked forGuidelines on which indications should be funded and whetherthe Society would endorse funding for Interferon for HepatitisC and provide guidelines for its use. The response wasrequested by 8 December to be tabled at the next meeting ofthe PTAC.
The Society of Gastroenterology advised that this deadlinedate could not be met.
19 October 1992 CSL wrote to the Auckland RBTS requesting advice of thedates when screening of plasma was started at all regionalcentres.
29 October 1992 Dr E Berry wrote to the Acting General Manager, AucklandArea Health Board, stating "This letter is to bring to yoururgent attention that PTX, the only Factor IX concentrateavailable in New Zealand has not been treated to inactivateHepatitis viruses. Risk of infection transmitted from thisproduct is estimated to be over 70%. Appropriatelyinactivated products are widely available internationally andcould be obtained for NZ patients. Such a product wasexpected to be available from CSL over a year ago but hasstill not been delivered." Dr Berry commented that she hadno budget to supply appropriate product to clients. DrBerry's letter was referred to the Board Solicitor for adviceabout Board liability.
Over the ensuing two weeks discussions and communicationoccurred between the Board solicitor and Dr Berry.
17 November 1992 In response to reports in the Dominion newspaper of that day- "Blood product feared to contain Hepatitis C", Dr JoanBaas, Therapeutics Section, Department of Health telephonedDr Peter Schiff, clinical Senior Manager, Blood ProductsDivision CSL to obtain background information on Factor IXto prepare a paper for the Minister.
INQUIRY REPORT 29
18 November 1992 Dr Arvind Pate! and Dr Joan Baas of the Department ofHealth telephoned Dr Woodfield to discuss issues relating tothe Factor IX products produced by CSL. Dr Woodfieldfaxed some questions for CSL and Dr Baas agreed totelephone Dr Peter Schiff regarding these questions.
A telephone conversation with Dr Schiff confirmed that
• an immediate supply of some Prothrombinex (60°C) fromAustralian blood could be supplied following an approvalfrom the Australian Red Cross.
• A supply of super heat treated product (80°C) fromAustralian blood (currently subject to approval forclinical trial) could be supplied, if requested by the NewZealand Department of Health, following approval fromRed Cross and the Therapeutics Goods Administration, theAustralian Authority.
• Dr Schiff agreed to contact Dr Woodfield regardingsupply of these products.
18 November 1992 Dr E Berry wrote to the General Manager, Auckland Hospitalstating that the Auckland Area Health Board solicitorrecommended the purchase of a supply of commercial productas soon as possible to cover the interim period until CSL canprocess New Zealand plasma appropriately.
19 November 1992 A facsimile was sent by Dr Baas to Dr Woodfield to confirmdetails of an earlier conversation on 18 November 1992 withDr Schiff. Dr Baas asked Dr Woodfield:
•to advise when the Australian sourced product wouldarrive in New Zealand, which product and quantity.
•to recall to consumer level the current Prothrombinexand advise how this was to be put in place.
Dr Baas advised Dr Woodfield that "there should be noarrangement for the supply of Factor IX product to NewZealand manufactured from unscreened blood unless agreedby the Minister".
20 November 1992 Facsimile from Dr Woodfield to Dr Baas advised that asupply of test 300 units of high heat treated Factor IX arebeing consigned to New Zealand today. Regional Directors
INQUIRY REPORT 30
have been asked to quarantine all existing stocks of Factor IX.
CSL telephoned the Department of Health, asking forauthorisation for export listing of the high heat treated FactorIX. Export listing is required by TGA as the product is notregistered in Australia.-
This meant that this product could not be consigned to NewZealand until listing had occurred. Therefore Dr Baas asked"CSL to immediately supply Prothrombinex (60°) to ensure asafe supply of Factor IX was immediately available".
A letter was faxed on behalf of the Department of Health,New Zealand to both TGA and CSL acknowledging that NewZealand would receive Prothrombinex H-T, even though theproduct is not a registered product in Australia. 300 units ofhigh heat treated Factor IX are to be dispatched to NewZealand in the next two weeks.
A facsimile was received from CSL to confirm that 100bottles of Prothrombinex (60°C) would arrive in NewZealand on 21 November 1992.
A facsimile was sent from the Department of Health to DrSchiff, CSL, confirming that the next batch of Factor IX to bemade from New Zealand blood will be prepared fromscreened plasma.
The foregoing is a selection of the more notable items pertaining to the mattersunder inquiry amongst the substantial volume of material made available to theInquiry.
INQUIRY REPORT 31
7First Term of Reference
ff To determine the circumstances surrounding the continued supply after 1 July1992 of a blood product which potentially exposed the users of that product to therisk of infection with Hepatitis C"
7.1Introduction of HCV Screening of Donated Blood
The Committee was advised that the date of 1 July 1992 was selected on the basisthat funds for testing of donated blood had been made available for the 1992-93financial year, commencing on that date.
Official notification of the commencement of HCV screening, dated July 1 1992,from the Department of Health was forwarded to all Area Health Board GeneralManagers. Second generation EIA test kits were received from the supplier in allRegional Blood Transfusion Centres during the week up to 27 July 1992, the delaybeing associated with the tendering process. Full screening of blood for HCVcommenced throughout New Zealand on July 27 when the kitsets were provided toall regional Blood Transfusion Services.
Partial screening had begun in some areas on their own initiative (Otago, Southland,Hawkes Bay, Taranaki, Rotorua) as early as mid 1991, when the second generationtest became available.
Screening of existing stocks of blood was undertaken in the Auckland, PalmerstonNorth, and Otago Regional Blood Transfusion services within one week of startingto screen new blood donations. Wherever possible, existing blood was not used. InCanterbury, including Timaru and Greymouth, unscreened blood was quarantinedand not used. Wellington began screening existing blood stocks on 23 September1992. Existing blood stocks were not screened in Waikato, but all products issuedafter 27 July 1992 were screened.
7.2 The Reasons for Continuing Risk
High heat treatment of blood products had been introduced in England by theElstree Laboratories in 1987. The methodology for these products was obtained byCSL in 1989. However, concerns developed relating to the potential increase inconcentrations of activated clotting factors as a result of this heat treatment, leadingto complications of thrombosis in patients receiving this product.
It was therefore necessary to modify the methods used to produce PTX H-T throughthe addition of Antithrombin III. A high heat treated Factor VIII (inactivatingHCV) was produced by CSL and available for use in New Zealand from mid-1990.The development of a safe and effective high heat treated Factor IX proved moredifficult and was not available for trial in Australia until March 1992.
INQUIRY REPORT 32
In March 1992, the Medical Director, Auckland RBTS, in a report of a visit toCSL, stated "It appears that all products could be registered under Section 23 of theAct, although final registration required section 20 specifications to be met.....Itwas suggested that Prothrombinex (high heat treated) should be releasedimmediately under Section 29 and that a Section 23 application should be lodged,but that would be unlikely to be completed until the end of 1992".
CSL had made inquiries about what approvals would be required in Australia toallow an unapproved product (ie, PTX H-T) to be issued to New Zealand patientson an individual patient usage (IPU) basis. CSL were advised that the productrequired listing on the Australian Register of Therapeutic Goods as an "export only"product and that this could not be achieved until the New Zealand Department ofHealth gave informed consent.
Successive contacts with CSL during 1992 reinforced the expectation that access toProthrombinex H-T from Australia was imminent.
Nevertheless the product has still not been approved by the Therapeutic GoodsAdministration in Australia and is available for use in Australia only under theAustralian Special Access Scheme.
Relevant New Zealand legislation, Section 29, Medicines Act 1981 states that anexemption allows a distributor to supply a product not otherwise covered underother provisions of the Act. In effect, it allows individual medical practitioners torequest a distributor to provide a product for named patients. If a product issupplied, the distributor must report at the end of each month to the Director-General of Health on the name of the product supplied, the practitioner requestingthe product and the patient to whom the product is supplied.
In the context of Section 29, a request to purchase CSL manufactured Pi'X H-Twould be directed or referred to the Auckland Regional Blood Transfusion Service,by virtue of its apparent responsibility to purchase CSL products on behalf of thecountry. That is, the Medical Director, Auckland RBTS is the "distributor". TheMedicines Act 1981 does not oblige the distributor to provide requested products.
Section 25 of the Medicines Act 1981 also provides for individual medicalpractitioners to sell, or supply, or procure for supply, products not currentlycovered under the Act. In effect, this allows any practitioner to go direct to CSL orto other overseas suppliers. Under the circumstances, no central funding wasavailable, and Area Health Boards had the responsibility to fund the purchase of theproduct.
There was no risk of Hepatitis C associated with other blood products, ieImmunoglobulin products, SPPS, Albumin or !actor VIII concentrates.
INQUERY REPORT 33
7.3Level of Recognition of this Continuing Risk
The fact that Factor IX made from blood unscreened for Hepatitis C continued inuse was clearly recognised by BTS Directors and clinicians.
7.3.1 BTS Directors:
It is said that the continued use of Prothrombinex made from plasma not screenedfor HCV was discussed at the July 1992 meeting of BTAC, although this is notrecorded in the draft minutes first made available to the Inquiry on 15 December1992, at its request.
Given that the circumstances were clearly well known to this group, it couldreasonably be expected that if any members of the group had considered that theproducts should have been withdrawn, they would have sought to have this recordedin the proceedings of the meeting.
We were advised in writing by the Medical Director, Auckland RBTS that:In July 1992, a similar situation developed with the blood services in New
Zealand as with the Australian Red Cross Society Blood Transfusion Services inFebruary 1990. There was little scientific or financial logic in withdrawing ordiscarding all non-screened HCV plasma collected in the first half of 1992 andexcluding it from the production of a product like Prothrombinex. Indeed, thiswould have probably led to a major supply crisis and would not have substantiallyreduced the infectivity of Prothrombinex for routine use.
Therefore, in view of the Australian experience .... and in the absence of a highheat treated product, no change in the procedures was made, ie, there was nowithdrawal of stocks of Prothrombinex made from non screened plasma. There wasalso no withdrawal of plasma in process for the production of Prothrombinex.
7.3.2 Clinicians:
Clinicians using the blood products were also aware of the problem which had beenongoing for 2 1/2 years. The product information sheet for Prothrombinex fromCSL clearly stated that heating to 60°C did not inactivate the Hepatitis C virus. Inaddition it is said that a leaflet had been produced and circulated widely withinhospitals in New Zealand to ensure that medical and nursing staff were aware of therisk, and a Haemophilia Society newsletter had also drawn attention to the fact. DrElizabeth Berry has stated that she always advised her patients of the risks.
Dr Berry, repesenting the Medical Advisory Panel to the Haemophilia Society, hadbeen seeking funding and clarification of the process for importing alternative, saferproducts for uninfected patients with Factor IX deficiency haemophilia since July1991.
INQUIRY REPORT 34
7.3.3 Department of Health:
There is no indication that any senior official in the Department of Health had beenalerted to the fact that Prothrombinex made from unscreened blood continued in usein New Zealand.
The 31 July 1992 letter from Dr E W Berry, when referred to the Department forthe preparation of a draft reply for the Minister, drew to the attention of somedepartmental officers, the continuing risk of infection associated with the lack ofavailability of high heat treated Prothrombinex, but any potential relationshipbetween this and the introduction of whole blood screening for HCV was notidentified.
7.3.4 Minister of Health:
There is no indication that the Minister or anyone in his office had become aware ofthe fact that Prothrombinex made from unscreened blood continued in use in NewZealand after 27 July 1992.
On 31 July 1992 Dr E W Berry wrote to the Minister of Health, alluding to theproblem that PTX from CSL, which remained heat treated only to 60°C and not to80°C, could contain HCV and could continue infecting new patients. Dr Berryreferred to the availability of other commercial Factor IX products which do nottransmit Hepatitis C, but noted that "no budgets have been developed in theRegional Blood Transfusion Service to buy such products". She concluded: "Themain purpose of this letter is to request the necessary funding to purchase suppliesof safe Factor IX concentrate until such time as appropriate local products come onstream."
The 4 September 1992 reply to Dr Berry from the Minister of Health, submitted indraft by the Department of Health on 31 August 1992, noted that blood transfusionservices are currently funded through Area Health Board bulk grants. In addition,the reply noted "the Department of Health makes an annual grant to the AucklandArea Health Board for purchasing, on behalf of the country, fractionated productsfrom CSL in Australia. Apart from that specific allocation, the funding that bloodtransfusion services receive is not tagged for any particular activity. The bloodtransfusion services, through the Area Health Boards, have the responsibility toprovide services that meet the health needs of people in their regions. I understandthe distribution and the monitoring of usage of Factor VIII and other products forthe treatment of haemophiliacs is already handled through the six regional bloodtransfusion centres. I consider that your organisation should discuss any issuerelated to the treatment of people with bleeding disorders with the regional directorsof the blood transfusion services. I will also refer your letter to the BloodTransfusion Advisory Committee for comment."
The issue that the blood product was a potential source of infection was notaddressed in the reply from the Minister.
INQUIRY REPORT 35
7.4The Inquiry finds that
Blood and blood products can never be 100% safe - that is, there can neverbe a zero-risk blood supply.
HCV screening of blood reduces, but does not completely eliminate the riskof HCV infection in blood.
Supply of Prothrombinex, a complex Factor IX blood clotting product,which was made from plasma unscreened for Hepatitis C, continued after 1July 1992.
Screening of blood for HCV, begun on 27 July 1992, would have reducedthe risk but not eliminated the possibility of infection. As the screening testwill not detect 2 in every 100 infected donors, and as up to 6,000 donationsare pooled to make one Latch of PTX, in the absence of super heattreatment, 33% of batches are likely to contain HCV.
HCV in Factor IX is partially inactivated if the blood product heated to 60°Cand more fully inactivated if the product is high heat treated to 80°C.
No approved and licensed alternative Factor IX product (heated to 80°C)was available in either Australia or New Zealand on 1 July. An unregisteredAustralian product was provided under special conditions on 1 December1992.
The fact that Prothrombinex made from blood unscreened for Hepatitis Ccontinued to be used after July 1, 1992 was not known either to the seniormanagement of the Department of Health or to the Minister of Health or hisoffice.
There is no evidence of a deliberate attempt to withhold information relatingto this situation.
ENQUIRY REPORT 36
8Second Term of Reference
ff To investigate what are the responsibilities and functions of the Office of theMinister of Health, the Department of Health, the Blood Transfusion AdvisoryCommittee and the regional Blood Transfusion Services and how those functions andresponsibilities inter-relate in respect of.
2.1 The provision of policy advice to the Minister of Health regarding the risk ofinfection with Hepatitis C resulting from receipt of fractionated bloodproducts; and
2.2 The facilitiation of the efficient and effective and safe acquisition anddistribution offractionated blood products in New Zealand.
8.1Responsibilities and Functions: (
8.1.1 Minister of Health
According to "Parliamentary Practice in New Zealand" by David McGee, nowClerk of the House of Representatives, "The Minister in charge of each Departmentis responsible for the conduct of the affairs of that Department"
Ministers are appointed by the Governor-General on the advice of the PrimeMinister. Ministers are also members of Cabinet which, while having few if anylegal powers itself, makes many decisions of a political or administrative naturewhich are then implemented by ministers in their individual capacities.
In practice, many other day to day policy and administrative matters are managedby Ministers without reference to other Ministers.
Prior to November 1990, the Minister of Health was Rt. Hon Helen Clark.
Since the current Government assumed office, the Minister of Health, Hon SimonUpton, has been assisted by two Associate Ministers. Their identifiedresponsibilities are respectively:
Hon Simon Upton
-Overall strategic direction of health sector.-Interim Targeting Regime.- Determination and structure of Vote:Health and expenditure priorities. (This
includes expenditure priorities for Area Health Board and independentservice provider contracts and health benefits).
-Core concerns relating to the Health/Welfare Interface.-Health research.-Environmental health.
INQUIRY REPORT 37
Hon Katherine O'Regan
-Child and adolescent health.-Health of older people.-Mental health.-Women's health-Communicable disease control.-Non-communicable diseases.-Health consumer rights.-Workforce issues.-Food and nutrition.
Hon Maurice Williamson
-Information technology and information systems.-Pharmaceutical and therapeutics.-Alcohol and drug abuse.-Smoke-free Environments Act.-Day-to-day management and signing of Area Health Board and independent
service provider contracts.
Each minister as a small number of policy advisers and support staff in his/heroffice.
8.1.2 Depwlinent of Health:
Section 7, Health Act 1963 states:"The principal functions of the Department of Health shall be -(c)to prevent, limit and suppress infectious and other diseases:(g) generally, to take all such steps as may be desirable to secure thepreparation, effective carrying out, and co-ordination of measures conducive to thepublic health:
The Director-General of Health has a performance agreement with the Minister onthe outcomes expected from the Department during the financial year. Thisperformance agreement is harmonised with the Mission Statement and Business Planof the Department of Health.
The mission statements of the Department of Health in 1990/91, 1991/92 and1992/93 outline the Department's responsibility "to be the Government's principalagent and advisor on health .....
The Department of Health has undergone three restructurings since 1989. The first,completed in February 1990 marked a major transition for the Department towardsbecoming a policy Ministry. A number of functions of a service delivery naturewere devolved to Area Health Boards. Subsequent reorganisations in July 1991 andOctober 1992 were to focus the Department more sharply in its policy advice role.
INQUIRY REPORT 38
Organisational charts indicate successive changes of structure, function andresponsibility. As a result of the structural changes, different sections have beensuccessively responsible for policy advice on blood transfusion services and forproviding secretarial support to the above advisory committees.
As a result of restructuring to focus the Department of Health as a policy ministry,service provision functions were separated from policy advisory functions. Somekey staff with medical/technical expertise were transferred to the Services Group.This resulted in a significant dearth of medical, technical or epidemiological inputto the development of policy advice.
8.1.3 Blood Transfusion Advisory Committee (BTAC)
BTAC was established by the Minister of Health in 1963 under section 13 of theHospitals Act 1957 to advise the Minister of Health on technical aspects of bloodtransfusion.
The members of BTAC are the Medical Directors of the six Regional BloodTransfusion Services. The Chairpersonship, a Ministerial appointment, is currentlyvacant. Since the resignation of the last Chairperson, effective 1 December 1990,four Departmental officials, responsible under successive Departmentalrestructurings for this function, have chaired BTAC meetings.
BTAC has three sub-committees to advise on matters of donor management andrecruitment, tissue typing, and technical matters relating to blood transfusion.
BTAC is an advisory committee to the Minister of Health. In past practice, it hasreported in writing to the Minister of Health and the Director-General of Health.
The work of two other advisory committees is also relevent to the Inquiry:- Communicable Disease Control Advisory Committee (CDCAC)- Medicines Adverse Reactions Committee (MARC)
CDCAC was established by the Minister of Health in December 1984 under Section9A of the Health Act 1956 to advise the Minister of Health on general mattersrelating to
- communicable disease control- sexually transmitted disease control- immunisation procedures and practices.
MARC was established by the Minister c' Health in 1985 under Section 8 of theMedicines Act 1981
- to advise the Minister of Health on matters concerning adverse reactions tomedicines
INQUIRY REPORT 39
- to oversee the collection and dissemination of information on adversereactions to medicines- to keep the medical and dental professions informed on adverse reactionsto medicines.
The area of mutual interest to all three advisory committees is the monitoring andcontrol of infectious diseases. Within the Department of Health, there are noformal linkages, accountabilities or advisory mechanisms between these threebodies. The principal line of communication is through Departmental officialscommunicating with colleagues on matters they perceive to be relevant to othercommittees.
8.1.4 Regional Blood Transfusion Services (RBTS)
There are six regional blood transfusion centres under the direct responsibility ofArea Health Boards, organised geographically alongside the major providers ofacute trauma/surgical/medical/oncology care in Auckland, Hamilton, PalmerstonNorth, Wellington, Christchurch and Dunedin. The six regional centres organiseblood donation/collection activities locally and supply appropriate blood and bloodproducts to meet local requirements. They also provide advisory and otherspecialist, services and co-ordinate the transfer of plasma to CSL, and thedistribution and supply of fractionated and rare blood products.
BTS Directors are employed by the Area Health Boards.
The Auckland RBTS acts as the co-ordination centre for some "national" servicesincluding the maintenance of banks of frozen rare blood types. It is also responsiblefor maintaining New Zealand's links with CSL and is the co-ordinator anddistributer of CSL products throughout New Zealand.
From the perspective of the issues under inquiry, it is difficult to separate the rolesof the Regional Blood Transfusion Services and the BTAC.
8.2 The provision of policy advice to the Minister of Health
8.2.1 Policy Advice and BTAC
BTAC is a Ministerial Advisory Committee.
The minutes of meetings of that Committee have not, at least in recent years, beensubmitted to the Office of the Minister (or to Associate Ministers) or to theDirector-General of Health. From time to time, the Chairmen of this Committeeand of CDCAC have written directly either to the Minister or to the Director-General on major areas of concern. At other times, it appears that letters to the
INQUIRY REPORT 40
Minister or to the Director-General were drafted by the secretary who is adepartmental officer.
In May and June 1991, Dr H W H Pullon wrote both to the Hon Mrs KatherineO'Regan and the Hon Simon Upton, on Manawatu RBTS letter-head and signed inhis capacity as Regional Transfusion Director, regarding issues which clearlyrepresented the opinions of BTAC rather than Dr Pullon as an individual. On 25July 1991, Dr Pullon wrote, signing on behalf of the Medical Directors of theRBTS, stated "If funding for Hepatitis C is not forthcoming, then we as RegionalTransfusion Directors will publicly absolve ourselves from the responsibility for thesafety of the blood supply in New Zealand".
The reasons that advice was provided by members of BTAC in their individualcapacities without the Committee's formal letterhead no doubt related to the failureto appoint a permanent Chairman to replace Mr G K Chapman who resigned inDecemb'r 1990.
This, in turn, could be attributed to the review of Ministerial Advisory Committeeswhich was conducted in early 1991 at the request of the Minister of Health. Thisreview recommended that BTAC be disbanded and its functions devolved to AreaHealth Boards. The response to these recommendations is not known.Departmental restructuring, taken together with the review, may have contributed tothe lack of priority given to BTAC affairs.
It is clear from the chronology 'recorded earlier that issues relating to the screeningof donated blood for Hepatitis C were brought to the attention of the Minister by theDepartment and a number of external individuals and organisations.
8.2.2 Policy Advice and the Depamnent of Health
The Department of Health provided policy advice to the Minister on the issue ofscreening throughout the period under inquiry. The Department used a number ofsources of information in the formulation of its policy advice to the Minister. Thesesources included BTAC, CDCAC and the New Zealand Communicable DiseaseCentre (NZCDC). Their recommendations were considered in the light of availableresources.
It is clear that from early 1990 there was a view commonly held by departmentalmanagers that the first generation EIA test was "not reliable enough ". It appears tothe Inquiry that the concepts of sensitivity and specificity of tests were not wellunderstood, and that considerable emphasis was placed on the number of falsepositives rather than on the fact that screening would enable 86% of the cases ofHepatitis C to be eliminated from the donor pool. This view was reinforced inMarch 1991 after the meeting of the General Manager, Services, with an official ofthe Centers for Disease Control, Atlanta and seems to have contributed to theapproach taken by the department to policy formulation in respect of testing donatedblood for Hepatitis C. This view was contrary to that of the BTAC, CDCAC, and
INQUIRY REPORT 41
published guidelines of CDC Atlanta as well as cost effectiveness studies producedin New Zealand.
Another factor influencing departmental policy was the process of devolution ofresponsibility and budget to Area Health Boards and the view of Ministers of Healththat it would be inappropriate to direct Area Health Boards on health priorities fortheir local populations.
Senior departmental officers could have been more aware of the level of concernamong medical and professional groups regarding the failure to introduce screening,if a senior medical member of the staff of the Department had been asssigned theresponsibility for broad oversight of the operations of BTAC.
BTAC minutes from 1991 record the committee's discussions of progress reports tmscreening for Hepatitis C, the availability of PTX H-T from CSL and other issuesrelating to the treatment of haemophiliacs. In the BTAC minutes of 11 April 1991,it was noted that " all haemophiliacs who are not known to be infected should betreated solely with super heat treated concentrates". However, there is no record offurther action on this statement.
Since the resignation as Chairman of BTAC of Mr G.K. Chapman in December1990, each BTAC meeting was chaired by a different departmental officer.
Departmental officials servicing the committee had insufficient medical/technicalknowledge to identify the issues. As a result, they were not alerted to communicatewith other knowledgeable officials in the Department.
Therefore, the Director-General of Health was not explicitly advised byDepartmental officials that there was a continuing risk of infection and was not in aposition to advise the Minister.
8.2.3 Policy Advice and the Regional Blood Transfusion Services
It is noted that two letters to the Minister of Health, written on behalf of theDirectors of the Regional Blood Transfusion Services, raised the issue of screening.There is no other indication of policy advice from the RBTS directly to the Ministerof Health.
8.3The Facilitation of the Efficient, Effective and Safe Distribution ofFractionated Blood Products in New Zealand
8.3.1 Relationship with CSL
The great majority of fractionated blood products are supplied from CSL inAustralia. A very small amount (4%) of Factor VIII is manufactured in Auckland.
INQUIRY REPORT 42
It is notable that the agreement between CSL in Australia and the New ZealandDepartment of Health has never been formalised beyond an exchange of lettersbetween Ministers in 1962 and the Director-General of Health and ManagingDirector of CSL in 1987.
Responsibility for negotiation with CSL is with the Director of the Auckland BloodTransfusion Service. It is unclear under what authority he has been given thisresponsibility, other than as the designated liaison officer from the BloodTransfusion Advisory Committee. In this role he has visited CSL on an annualbasis and reported back to BTAC on any matters relating to the supply ordevelopment of blood products. The Auckland Area Health Board requires theRegional Transfusion Director to develop a yearly budget for blood products basedon assessments of the needs of each region. Information is obtained from individualregional transfusion directors and collated, costed and forwarded to the AucklandArea Health Board which then negotiates with the Health Department as to theavailability of funding. The budget for purchase of blood products from CSL hasbeen added to the budget of the Auckland Area Health Board, although reference tothis in the contract of the Auckland AHB is not detailed.
The Director's lines of responsibility for this activity remain unclear. His majorresponsibility for the Auckland Regional Blood Transfusion Service is to theAuckland Area Health Board which, although in receipt of tagged funding, has notbeen formally given responsibility for negotiating with CSL.
No senior departmental officer has been identified as having any responsibility forthe oversight of the negotiations with CSL, and therefore, apart from his reportingto BTAC, no clear channel of communication between the Director of the AucklandRBTS and the Department of Health exists in respect of his national responsibilities.
It is apparent that apart from information obtained at BTAC meetings by thoseacting as Chairman, issues relating to the delay in production of 80°C treatedProthrombinex by CSL have not been brought to the attention of the Department.
The Director of the Auckland RBTS has thus assumed responsibility for theefficient, effective and safe acquisition and distribution of fractionated bloodproducts in New Zealand. The exchange of letters in 1987 bound him to acontinued dependence on CSL for supply of these products.
There is currently no indication of whether the present arrangement for supply offractionated blood products is the most efficient, effective or safe.
The possibility of developing a plant in Auckland which would allow New Zealandto be self sufficient has been previously considered and rejected. Obviously thisoption could be explored again if circumstances change.
There is no information available to indicate whether other countries would be ableto provide a more efficient or effective service than Australia.
INQUIRY REPORT 43
It is known that a high heat treated Prothrombinex was first trialled in the UnitedKingdom in 1987 but that this product is not available for export.
It is noted that in 1989, Dr Woodfield wrote to the Chairman of BTAC indicatingthat he had explored alternative ways to obtain blood products and sought advice onwhether such alternatives would be acceptable. He specifically mentioned a veryattractive offer from France to process NZ cryoprecipitate into a high qualityproduct at a price, conservatively, one third less than that charged by CSL. Whileno reply to this suggestion has been located, it would appear that it was notfollowed up.
It is understood that Factor IX deficient haemophiliacs are still using routine PTXmade from Hepatitis C screened plasma.
It is also noted in November 1992 that communications between the AucklandRBTS and CSL recognised that haemophiliacs were demanding the import ofAmerican products. It is also clear that this option was viewed with considerableconcern by many clinicians as well as transfusion specialists, on the grounds thatcommercial products derived from purchased plasma which has caused problems inthe past, may carry yet undetected viruses.
The close professional links with Australia and communication issues provide anumber of advantages which are unlikely to be matched by any other country whichmay offer a product at lower price.
Nevertheless it is obviously essential that a contract be developed between CSL anda New Zealand body which has a clear national responsibility in relation to bloodproducts.
It is understood that a draft contract has been drawn up and is currently beingconsidered by BTAC.
8.3.2 licensing Under the Medicines Act
Another issue of continuing concern is the fact that fractionated blood products havenot been registered as Medicines under the Medicines Act 1981. Blood and bloodproducts are required to be registered as medicines, although the Inquiry is awarethat there has been on-going debate about the desirability of this classificiation. Inorder for registration to occur, blood processing centres need to be licensed underthe Medicines Act, for the manufacture of medicines. The purpose of suchlicensing is to demonstrate that processing centres have the appropriate facilities andprocesses for the collection and manufacture of blood and blood products. Thelicensing requirement was to have been implemented by August 1985, laterextended to August 1986. Because of difficulties in preparing agreed standards ofthe collection and manufacturing processes, no processing centre has yet beenlicensed.
INQUIRY REPORT 44
The Inquiry understands that the Department of Health is considering the adoptionof the Australian Standards for Good Manufacturing Practice as applied to thelicensing of blood processing centres and that licensing will commence in 1993.
Blood products from CSL used in New Zealand are required to be, but are not atpresent, registered under the Medicines Act 1981. Submissions on each producthave been recieved from CSL, and are still in the process of assessment by theTherapeutics Division of the Department of Health.
8.4The Inquiry finds that
•There are no clearly defined lines of communication for transmission of policyadvice to the Minister on issues relating to blood transfusion.
•BTAC was left without a Chairman or access to senior levels of theDepartment of Health or to the Minister of Health.
• As a result of numerous departmental reorganisations, there was no seniordepartmental officer with a knowledge of clinical issues, who was aware of theproblems faced by BTAC and the complex scientific problems involved inmaintaining a safe and effective supply of blood products in New Zealand.
• Responsibility for negotiation with CSL for the acquisition and distribution offractionated blood products in New Zealand was loosely delegated to theDirector of the Auckland RBTS.
•There is no formal contract between CSL and New Zealand for the supply ofblood products worth over $6 million per year.
INQUIRY REPORT 45
9Third term of Reference
"Report to the Director-General of Health on the results of your inquiry makingrecommendations as appropriate regarding:
3.1 Any changes to processes for the preparation and submission to the Ministerof Health ofpolicy advice relating to blood and blood products; and
3.2 Any changes to the responsibilities and functions between the office of theMinister of Health, the Department of Health, the Blood transfusionAdvisory Committee and the Regional Blood Transfusion Service and theirinter-relationships that are necessary to facilitate the acquisition anddistribution of blood and blood products in an efficient and effective and safeway (bearing in mind the Government's proposals for the reorganisation ofthe Blood Transfusion Service)."
9.1Proposals for reorganisation of BTS
The National Interim Provider Board was commissioned to study the future optionsfor organising blood transfusion services in New Zealand, within the context of theoverall health sector reforms. The government has made decisions based on thefindings and recommendations of this consultancy project.
Four regional blood trusts will be formed which will be responsible for obtainingthe required products on contract from BTS organisations, and ensuring their supplyto health service providers. They will be not-for-profit, charitable trusts,administered by separate boards of trustees.
Each trust will determine its own executive staffing and accommodationarrangements. The trusts will have the same boundaries as regional healthauthorities (RHAs) and may develop close relationships with RHAs. The trusts areexpected to be very small, employing only a small number of staff. It is envisagedthat they will cooperate with each other to develop a joint contract with CSL forfractionated products.
The Ministry of Health will be responsible for setting, monitoring and enforcingminimum safety and quality standards. The Minister of Health will have the powerto grant permits for the collection of blood to the trust on therms directed by theMinister. The trusts will then arrange for the collection of donated blood within theagreed collection area and for testing, processing and storing blood and bloodproducts.
A national BTS committee will be formed to supervise and monitor the BTS as awhole and oversee the overall operation of each trust. It will report to the Director-General of Health and will also advise on BTS policy matters.
BTS centres and sub-centres will remain in CHEs and they will contract with theblood trusts. Over time, other organisations such as private laboratories andvoluntary organisations may also contract to provide BTS services.
INQUIRY REPORT 46
9.2 Proposals for Change
It is important that any proposals for change to responsibilities and functionsrelating to blood transfusion services or to systems for the supply and distribution ofblood products are compatible with the general health reforms taking place in NewZealand.
The Inquiry has had access to the final report to the National Interim ProviderBoard on "Future Configuration Options for Blood Transfusion Services" preparedby Coopers and Lybrand Consultants and to the submissions made to theconsultants. The extensive work undertaken by the Consultants is recognised andobviously the Inquiry has not in any way been able or even attempted to considerthe issues in the detail undertaken by the Consultants.
The Inquiry has, however, highlighted a number of issues which need to be takeninto account in the proposed reorganisation.
9.3Term of Reference 3.1 - Policy Advice to the Minister
The Inquiry finds that
• There should be a Committee charged with the development of nationalpolicy and standards for the Blood Transfusion Service. This Committeeshould comprise representatives from blood transfusion service directors,clinical haematologists, Regional Health Authorities, the Principal MedicalAdvisor, Department of Health and a consumer.
• The Committee should more appropriately advise the Director-General ofHealth rather than the Minister of Health in order to ensure that appropriatepolicy can be developed taking into account other competing priorities.
•Nevertheless, the Committee should retain the option to approach theMinister of Health directly on matters of concern.
9.4 Term of Reference 3.2
The Inquiry finds that
• There are some distinctive features about Blood Transfusion Services whichrequire them to be considered in a somewhat different context from mostother health services.
INQUIRY REPORT 47
• There is a need for the services to retain a local focus, firstly to facilitatedonor recruitment and retention, and secondly to maintain close relationshipswith clinicians, the users of the products, in order to ensure appropriateusage and quality control.
There is also a need for a strong national focus.
- National standards for good manufacturing practice of blood andblood products need to be adopted and monitored.
- Decisions on policy for issues such as screening need to be made at anational level.
- There needs to be a clearly identified body which takes totalresponsibility for all issues relating to the acquisition and supply ofblood and related products for New Zealand.
- There are likely to be financial as well as quality advantages inpurchasing blood products nationally.
Transfusion medicine is a highly specialised and rapidly advancing field. It isimportant to limit responsibility for transfusion services to a small number ofappropriately qualified staff whose expertise can be maintained and developed
Links should be maintained between any body charged with the developmentof national blood transfusion policy and the senior medical advisor to theDepartment to ensure that senior departmental officers are aware of anydeveloping issues requiring a policy response.
A contract should be signed with CSL, with regular review at appropriateintervals, to formalise the arrangements between Australia and New Zealand.
INQUIRY REPORT 48
10 RECOMMENDATIONS
There is a need for a national committee to take responsibility for thedevelopment of policy and standards, the monitoring of standards and theprovision of advice to the Department and the Minister of Health on issuesrelating to blood and blood products.
2 The Principal Medical Advisor to the Department of Health should beresponsible, within the Department of Health, for overseeing issues relatingto blood and blood products.
3A contract should be formalised with CSL for the supply of blood productsfor use in New Zealand.
4 The Department of Health should request the manufacture and supply ofhigh heat treated Prothrombinex, sourced from New Zealand plasmascreened for HCV, from CSL at the earliest practicable opportunity.
5Steps should be taken by the Department of Health to ensure appropriatemedical and technical input into health policy.
INQUIRY REPORT 49
APPENDIX 1
Those whom the Inquiry met and/or received submissions from:
Dr J W Baas Advisor (Science)TherapeuticsDepartment of Health
Mr N H Barrett PartnerCoopers & Lybrand ConsultantsAuckland
Dr E W Berry Physician-in-Charge(and Barrister W G C Templeton)Haemophilia Centre
Auckland Hospital
Dr G R Boyd Manager, TherapeuticsDepartment of Health
Mrs .L Caroll National Director of ServicesKIDS FOUNDATION
Rt Hon H Clark Member of Parliament for Mt AlbertFormer Minister of Health
Ms A M Dixon ManagerHealth Sector Provider Policy
Dr J M Faed Regional Transfusion Director
Dr Garry Forgeson
Emeritus Professor F N Fastier
Mrs J M Glackin
ENQUIRY REPORT
ChairmanNew Zealand Clinical Oncology Group
Member, Toxic Substances Board
Analyst
50
Disability Support ServicesDepartment of Health
Dr L F Haas Honorary SecretaryNew Zealand CommitteeThe Royal Australasian College ofPhysicians
MrDKHunn Commissioner
State Services Commission
Mr L losefa AnalystPersonal Health ServicesDepartment of Health
Mr I T Johns
Mr A Jones
Mr J C Lovelace
Mr M R Mapperson(and Barrister W G C Templeton)
Mr J Martin
Dr J R D Matthews
General ManagerPolicyDepartment of Health
Policy AdvisorOffice of Minister of Health
Director-General of Health(26/1/92 - present)
PresidentNew Zealand Haemophilia Society Inc
Senior Lecturer in Public PolicyVictoria UniversityWellington
PresidentAuckland DivisionNew Zealand Medical Association
Mr I H Miller Acting Director-General of Health
(1/4/92 - 26/1/92)
INQUIRY REPORT 51
Dr P A Ockelford
PresidentNew Zealand Society for Haematology
Hon K V O'Regan Associate Minister of Health
Dr A C Patel Senior Advisor (Community Medicine)Health Regulation and Protection GroupDepartment of Health
Dr R B Ellis-Pegler
Mr R Ritchie
Dr G C Salmond
Infectious Disease PhysicianAuckland
Former ManagerHealth Services PolicyDepartment of Health
Former Director-General of Health(1985 - 28 March 1991)
Dr P Schiff Clinical Services ManagerBlood Products DivisionCSL Ltd (Australia)
Dr A J Scott Chairman of Assembly
New Zealand Medical Association
Associate Professor C Tasman-JonesDepartment of MedicineUniversity of Auckland
Mr G V Taylor Deputy CommissionerAuckland Area Health Board
Mr M Templeton Chief Executive OfficerInstitute of Environmental Health andForensic Science
INQUIRY REPORT 52
Mr W G C Templeton
Hon S D Upton
Dr D G Woodfield
Barrister, Auckland
Minister of Health
Medical DirectorDepartment of Transfusion MedicineAuckland Regional Blood Service
Hon M Williamson Associate Minister of Health
ENQUIRY REPORT 53
APPENDIX 2
HEPATITIS C SCREENING OF BLOOD DONATIONS
A CHARACTERISTICS OF THE SCREENING TEST
The two basic characteristics of a screening test are its sensitivity andspecificity.
Sensitivity tells us how good a test is at correctly Identifying people whohave antibodies to Hepatitis C. For example, a sensitivity of 80% meansthat 8 out of every 10 people who truly do have the antibodies will have apositive test, and two will have a negative test.
Specificity tells us how good a test is at correctly excluding people who donot have antibodies to Hepatitis C. For example a specificity of 99% meansthat 99 out of every 100 people who truly do not have antibodies will have anegative tes, and the remaining person will have a positive test.
Sensitivity = True positives I true positives plus false negatives
= True positives / all those with the disease
Spec jflcity = True negatives I true negatives plus false positives
= True negatives / all those without the disease
Sensitivity (in percent) = A / A+C X 100
Specificity (in percent) = D I B+D X 100
BFIRST GENERATION HCV ANTIBODY (anti-HCV C100) ASSAYS:
Abbott specifications gave:
sensitivity:in acute cases62%
(i.e. 62 out of 100 cases of acute Hepatitis C had a positive test while 38patients who also had Hepatitis C, had a negative test)
in chronic cases85.7%
INQUIRY REPORT 54
(i.e. approximately 86 patients out of 100 with chronic Hepatitis C had apositive test while 14 who also had chronic hepatitis had a negative test)
specificity 98.9%
(i.e. approximately 99 out of 100 patients without Hepatitis C infectionwill test negative; however one patient , without Hepatitis C,will testpositive.)
SECOND GENERATION anti-HCV EIA ASSAYS;
sensitivityin acute cases68.6%
(i.e. approximately 69 patients out of a 100 with acute Hepatitis C infectionhad a positive test while 21 patients also with acute Hepatitis C testednegative)
in chronic cases98.0%
(i.e. 98 patients out of 100 with chronic Hepatitis C infection had a positivetest while 2 patients who also had chronic hepatitits C tested negative)
specificity 99.5%
(i.e. almost 100 patients out of 100 without Hepatitis C infection will testnegative)
LIKELIHOOD OF BLOOD PRODUCTS BEING INFECTED WITHAN AGENT EXPRESSED AS A PERCENT OF BATCHES PREPARED
Hepatitis CPrevalence1:1001:5001:1,0001:2,0001:5,0001:10,0001:15,0001:30.000
Number of Blood Donations Pooled toge5001,0002,0004,00099%>99%>99%100%63%87%98%>99%39%63%87%98%22%39%63%87%10%18%33/555%5%10%18%33%3%7%13%23%>2%3%6%13%
batch
100%>99%>99%95%70%45%33%18%
INQUIRY REPORT 55
APPENDIX 3
SUMMARY OF RESEARCH CONSIDERED BY THE INQUIRY
1. Aust. N.Z.J. Med. (1982( 12, pp. 268-271
Prospective study on 94 patients, urban New Zealand. Analysis of sera with26(27%) acute HB; 22(23%) had acute HA and 25(26%) had acute NANBH; 9(10%) had EBVH (Epstein-Barr Hepatitis) and 1 (1%) had CMVH(cytomegalovirus infection).
2. Berlin: Springer, 1982:24-32
Hepatitis B virus markers were found in all patients treated with annual doses of10,000 or more Factor VIII units.
3. Br. J. Haematol 1985; 60:469-79
There was a 100% prevalence of NANBH, diagnosed by the presence of raisedaminotransferase levels after infusion and by the exclusion of other causes ofhepatitis, in patients who were at high risk of infections because they had notpreviously received any blood or blood-product
4. Am J Haemato 1986; 23:295-305
The almost constant occurrence of post-transfusion hepatitis in patients givenunheated pooled concentrates of plasma, and concern about the transmission byblood products of the HIV, have prompted manufacturers to develop procedures(usually based on various methods of heating the concentrate) for inactivatingviurses with little loss of labile Factor VIII activity.
5. NZ Med J 1987; 100: 99-102
303 cases of viral hepatitis identified over 4 month period. 49(16.2%) HA, 88(29%) HB, 80 (26.4%) NANBH, 81(26.6%) EBVH, 5 (1.6%) CMVH. Incidenceof acute symptomatic viral hepatitis was 78 cases/105 I per year for the Aucklandregion.
6. NEJM 1987; 316; 918-22
Post-transfusion hepatitis is frequent among patients with haemophilia who aretreated with concentrated Factor VIII prepared from pooled plasma. A multicenterprospective sutdy to learn whether post-transfusion hepatitis would occur inpreviously untreated patients with haemophilia who were given infusions of acommercial Factor VIII concentrate that had ieen heated in solution (wet-heated) at60°C for 10 hours in the presence of substances that stabilize Factor VIII activitywas undertaken. This heating process, commonly called pasteurisation, is known toeliminate the risk of transmission of infection from blood products, such as albumin
INQUIRY REPORT 56
and plasma protein fraction, that are less labile than Factor VIII. In this study, nohepatitis occurred after infusion of 32 batches indicating that pastuerisationminimizes the risk of post-transfusion hepatitis.
7. TRANSFUSION 1987; 27, No. 6:447-448
The availability of a testing technology or a donor screening methodology does notnecessarily mean the resources to implement such procedures should be expended.Unless the efficacy of the procedure has been firmly established, these monieswould be better invested in improving the way in which we do things of provenefficacy in reducing transmission of HIV-1 and other infectious agents throughblood transfusions.
8. Science 1989;244:359-62
Choo et al created a complementary DNA library from a concentrate of plasmataken from chimpanzees infected with NANBH. By screening approximately onemillion clones agaist sera of patients clinically infected with NANBH, theinvestigators isolated a single complimentary DNA and called it the "C100 antigen".
9. Science 1989;244:362-4
A radioimmunoassay was found to be positive in six of seven patients with chronicNANBH and negative in patients without disease. A colorimetric enzyme-linkedimmunosorbant assay (ELIZA) screening test was developed and introduced. Apatent was taken out by the Chiron corporation.
10. Hepatitis C Antibody results in Sydney blood donors, Sept. 1990
Incidence of approximately 0.8% of Sydney blood donors to be repeat reactives (apositive result initially and on repeating the test) using the Abbott ELISA C100screening test.
In Queensland and Northern Territory the Ortho ELISA C100 test showed anincidence of approximately 0.6% of blood donors to be repeat-reactive.
Discrepancies between the Abbott and Ortho tests are mostly in the low S/CO range(less than 2) and it seems likely that these discrepant repeat reactives arefalsepositives. Results in Sydney have shown approximately more than half of Abbottrepeat reactives in the low S/CO range to be negative by the Ortho Elisa Test.
A confirmatory test known as the Chiron Strip RIBA Test has been developed and isbeing marketed by Ortho. Results on Abbott ELISA C100 positive donor samplescollected in Sydney have shown approximately 25% to be positive by the RIBAconfirmatory test.
INQUIRY REPORT 57
Anti-HCV in Sydney Blood Donors
TEST NO.NO.% REACTIVESTESTEDREPEAT IN DONOR
REACTIVE POPULATIONAbbott Elisa C100 Test 46,7343620.77Ortho Elisa C100 on Abbott 3622370.5ReactivesRIBA confirmatory Test on Elisa 15637 0.2C100 reactivce samples from16,998 donations
11. Post Transfusion NANBH in New Zealand, 1990DG Woodfield, Medical Director Auckland Regional Blood Centre
The rate of detecting HCV antibody in random New Zealand blood donors is0.47%. Personal communication with Abbott laboratories suggests on the basis ofconfirmation assays that the true figure may be 1/3 lower, i.e. 0.31%.
In New Zealand approximately 103,000 units of blood are transfused yearly. 319units would therefore test HCV antibody positive. It is known that 50-90% ofHCV-infected blood units will transmit this infection. Assuming that 70% of HCVantibody positive blood units are infective, and each patient receives 1 unit of HCVantibody positive blood, there would be 223 patients (70% of 319) infected.
Approximately half these patients will be deceased within 1-2 years from othercauses leaving 112 patients who are infected with the virus. Only 28 (25%) of thesepatients would have clinical evidence of acute post transfusion hepatitis C.
Given that 50% of patients who receive infected units of blood will develop chronichepatitis, and 20% of these cirrhosis, this means that 56 patients per year maydevelop chronic active hepatitis and 11 patients cirrhosis.
Some groups of patients, e.g. haemophiliacs, are treated with pooled bloodproducts. Such persons are at greater risk of infection and sutdies have shoen avery high prevalence of HCV infection (over 75%). Such groups of patients willthis eventually show an even higher frequency of chronic hepatitis and cirrhosis.
Prevention by HCV antibody screenign of all donor blood would seem an importantoption if confidence in the safety of the blood donor system is to be maintained.
The alternative will be a substantial increase in expensive autologous and directedtransfusion programmes, a shortage of volunteer blood and the development of alower standard of blood transfusion in New Zealand.
INQUIRY REPORT 58
12. Discussion Paper for CDCACDr. N Wilson, NZCDC, 27 June, 1990
The results of this analysis suggest that screening is a very cost effectiveintervention compared to many other comon activities in the haelath sector. Theother benefits of screening in terms of preventing suffering and preventing loss ofconfidence in the blood supply, were considered to far outweigh potential adverseeffects.
Although the benefits to the reipeients of specialised blood products (e.g.haemophiliacs) were not quantified, these were also considered to be significant.
Recommendations:
1 that the CDAC recommend to the Minister of Health the immediate fundingof a nationwide screening programme of blood for transfusion for hepatitis Cantibodies.
2 that it be recommended that the funding for screening be in addition tocurrent Area Health Board funding so that screening can be implementedrapidly and uniformly across the nation.
3that further research be recommended on the legal issues of not screeningand the ethical issues related to informing donors infected with hepatitis C.
4 that as a general measure to reduce transfusion acquired infections, theCDCAC recommend that Area Health Boards pay more attention to qualityassurance and audit in the area of blood transfusion.
13. Recommendations for Testing for Antibody to Hepatitis C Virus encodedantigen (anti-HCV) in Blood Establishments, Division of Transfusion Science,Laboratory of Blood Bank Practices. November 1990, FDA.
I.Performance of anti-HCV testing
1. a single EIA test should be performed on a donor sample foreach unit of whole blood or component intended fortransfusion (the initial test).
2. if the initial test is nonreactive the donor sample is considerednegative for anti-HCV.
3. if the initial test is reactive, the donor sample is considered tobe initially reactive. The sample should be retested induplicate in a single test run, using a test kit from the samemanufacturer of the kit used for the initial test.
INQUIRY REPORT 59
a. if both duplicate repeat test results are nonreactive, thetest is considered to be negative for anti-HCV
b. if either one or both of the duplicate repeat test resultsare reactive, the test is considered to be repeatedlyreactive for anti-HCV and the products should not beused for transfusion.
II.Plasma for further manufacture
Source Plasma: The FDA does not currently recommend that Source Plasmadonors be tested for anti-HCV. Plasma from thousands of donors is pooled for themanufacture of plasma derivatives; although current tests identify the majority ofHCV carriers, the testing of individual units for anti-HCV will not eliminate allhepatitis C virus contribute to the safety of certain plasma fractions, such asImmune Globulin and Immune Globulin Intravenous. The safety of immuneglobulin products experimentally manufactured from anti-HCV-depleted plasmapools is being studied.
VII. Other Measures against Post-transfusion Hepatitis
Anti-HCV testing is not expected to eliminate all case of post-transfusion hepatititisC. Therefore, the FDA suggests that blood establishments continue all measuresimplemented previously to reduce the risk of post-transfusion hepatitis.
14. SCIENCE, vol. 248; 4 May 1990:559-564
Advances in low-level risk detection threaten to engulf us with information.Regulators typically respond to each newly highlighted risk, whether painstakinglyuncovered through scientific investigation or divulged with fanfare by the media, onan ad hoc basis. This response makes it hard to relate disparate risks to the overallrisk level and impedes intelligent risk reduction, which must consider the costs andbenefits involved.
We needto acknowledge that risks to life and limb are inherent in modem society—indeed in life itself—and that systematic strategies for assessing and responding torisks are overdue. Such strategies will involve significant reassignment of decision-making responsibilities. Individuals should do more for themselves, paying greaterattention, for example, to their diets and driving habits. Governments should focusless on microscopic contingencies, and more on human mistakes and misdeeds, thesource of far greater risks.
15. JAMA, November 7, 1990;Vol 264, No. 17:2231-2235
This study indicates that HCV is responsible for the majority of NANBH in theUnited States. Most cases are not associated with blood transfusion, and only halfhave a defined parenteral exposure. Further definition of the role of sexual
INQUIRY REPORT 60
transmission and inapparent sources of infection is needed to develop preventativemeasures that will have an impact on disease outside of the transfusion setting.
16. Hepatology 1990 12:671-75
These data suggest the slow, sequential progression from acute hepatitis C virusrelated NANBH through chronic hepatitis and cirrhosis to hepatocellular carcinomaand support a causal association between hepatitis C virus and hepatocellularcarcinoma.
17. NZ Med J 12 Sept 1990; Vol 103, No 897:421-422
There is this evidence that:(1) NANBH and hence almost certainly hepatitis C is an issue in New Zealand,(2) Hepatitis C can be transmitted sporadically and by transfusion;(3) While it may cause an acute hepatitis, subclinical infection also occurs,(4)There is a high incidence of chronic active hepatitis, cirrhosis and hepatocellularcancer following exposure to the hepatitis C virus,(5)Hepatitits C may be pivotal in determining the outcome of excess alcohol indamaging liver,(6)A hepatitis C antibody diagnostic test is available. Preliminary studies suggestthat it is a reliable test for diagnosing current infection and evaluating treatment.(7) Alpha interferon may have a place in the management of patients with chronichepatitis C.(8) liver transplant may be the only therapeutic option for some patients withchronic hepatitis C infection.
Early consideration should be given to:(1) Mandatory testing of all transfusion blood and blood products for the presenceof HCV antibody,(2) Surveys should be made to show the relative incidence of hepatitis C in selectedpopulations,(3) Interferon should be available for treatment of hepatitis C in selected clinicalresearch units,(4) The relative importance of hepatitis C in chronic liver disease should beascertained by appropriate supported research.(5) A national policy on liver transplantation should be developed.
18. NFJM 1990;322:1107-1112
This paper was reviewed in GASTROENTEROLOGY Vol. 100, No.3:March 1991:839-841
Comment stated that the NEJM study clearly demonstrates that HCV infection canoccur as a consequence of transfusion with anti -HC V -negative blood. Therefore,the current anti-HCV ELISA (C100) test is not sufficiently sensitive to detect allinfectious donors. The observation that longitudinal testing of anti -HCV -negative
INQUIRY REPORT 61
donors implicated in HCV transmission uncommonly shows late seroconversionindicates that implicated donors may be viraemic for prolonged periods withoutdetectable anti-HCV. Better assays for detection of HCV-infective donors areneeded.
19. Blood Reviews (1991) 3, 234-239
The incidence of post-transfusion hepatitis (PTH) varies over an order of magnitudein different parts of the world. For example, prospective studies from Spain andthe UK reveal rates of PTH of approximately 10 and 0.5% respectively. Similarlythe association of a history of transfusion in patients with chronic liver diseasevaries widely; in Japan, with high rates of P ITH, the association appears obviouswhereas in the UK less obvious. These factors must be taken into account whenassessing the cost-effectiveness of pre-transfusion screening for HCV. A usefulapproach to assessing the vaue of screening donors for anti-HCV is to studyprospectively the correlation of anti-HCV and PTH. In carefully selected cases ofPTH, the correlation of anti-HCV and PTH in donor-recipient sets of samples maybe very high. However, the predictive value of 'first-generation' assays for anti-HCV in routine studies of unselected cases of PTH may be less than 20% incountries with low rates of transfusion-transmitted NANBH.
The anti-HCV screening tests and supplementary assays are continually evolving.More recent assays incorporate structural as well as non-structural antigens in bothtypes of ELISA used for screening and in the supplementary tests such as therecombinant based immunoblots. The polymerase chain reaction (PCR) is alsovaluable for confirmation of viraemia but a negative result does not rule out thepossibility of the presence of antibody in the absence of virus; nor can it rule out thepresence of virus in very low levels in the blood stream, although virus may bepresent at a higher level in the liver or other tissues. However, these highlysophisticated supplementary assays are very expensive and their value ascomponents of mass screening programmes must be assessed for each individualcountry before they are implemented.
20.THE LANCET vol 338: Oct 26, 1991:1040-1041
Screening for HCVAb clearly contributed to the decrease in PTHC even though theHCVAb screening kit that we used is not sensitive enough to identify all unitsinfectious for HCV. In the hope of providing more complete protection againstPTHC, we are now investigating more sensitive screening tests with other HCV -antigens.
21. Annals of Internal Medicine 15 Oct 1991; Vol 115; No. 8:596-600
In our study, the relative risk for hepatitis in recipients of anti-HC V-positive bloodwas almost 20 times greater than that in recipients of seronegative blood. Exclusionof anit-HC V-Positive blood could have prevented 80% of case of PTH.
INQUIRY REPORT 62
15% of our patients who develped NANBH had received transfusions of anti-HCV-negative blood. Our findings indicate that some infectious HCV carriers escapedetection by ELISA (C 100) and suggest that more sensitive tests are needed toimprove efficacy of screening blood donors for HCV.
22. Hepatology 1991; 14:90 A (abstract)
Half of acute NANB TAH (transfusion associated hepatitis) cases are reported toadvance to chronic hepatitis with histologic sequelae of chronic active hepatitis in50% and cirrhosis in 20%. Hepatocellular carcinoma appears also to be anendpoint, particularly in Japan. In the United States, the natural history of NANBTAH is not well defined. Our study concludes that mortality from cirrhosis andhepatocellular carcinoma in patients with NANB TAH is not increased an averageof 18 years after hepatitis. Alcohol may effect liver-related mortality.
23.NEJM Feb 7, 1991; Vol 324 No. 6: 370-384
We identified 3.7 % of randomly selected patients (from hospital records) withdisabling injuries caused by medical treatment. The proportion of adverse eventsdue to negligence was highest for diagnostic mishaps (75%), noninvasivetherapeutic mishaps ("errors of omission") (77%), and events occurring in theemergency room (70%). Errors in management were identified for 58% of theadverse events, among which nearlyhaif were attributed to negligence.
We conclude that although the prevention of many adverse events must awaitimprovements in medical knowledge, the high proportion that are due tomanagement errors suggests that many others are potentially preventable now.Reducing the incidence of these events will requeire identifying their causes anddeveloping methods to prevent error or reduce its effects.
24. The Western Journal of Medicine Jan 1991;154:91-92
Approximately 0.4% to 1.5% of volunteer blood donors have a reaction with thistest [ELISA C100-3]. It is estimated that the use of this screenign test will furtherdecrease the rate of transfusion-transmitted NANBH by at least 50%.
As many as 40% to 60% of the reactions in blood donors are false-positive—that is,unrelated to hepatitis C. Among populations at high risk for NANBH, however,such as persons with haemophilia, almost all reactions are confirmed. Preliminarydata suggest that the results of these confirmation tests correlate with infectivity.
25. Report of Hepatitis C Workshop NZCDC, March 1992
Testing• first generation assays only identified an antibody to a non-structural (C100)
protein of the virus.• these assays were useful in drawing attention to hepatitis C but were not
sensitive or specific enought to accurately determine prevalence rates.
INQUIRY REPORT 63
• "second generation" assays now available detect antibodies to structural andnon-structural viral proteins. They have increased sensitivity and specificity,but are still imperfect. New assays are being developed.
• "confirmatory" antibody assays are also available.These decrease thepossibility of false-positive results.
• a positive antibody result indicates that the patient has been exposed to HCV butcannot reliably distinguish between acute, chronic or resolved infection.
• a polymerase chain reaction (PCR) based assay for detection of HCV RNA hasbeen developed. This is a sensitive marker for viraemia and can thereforeprovide further information about the hepatitis C status of an infected individual.
RecommendationsBlood Transfusion Services• it is recommended that all donations of whole blood intended for homologous or
autologous transfusion be tested for anti-HCV.• testing of blood donations and donors should be kept under regular review by
the Blood Transfusion Advisory Committee.• a regualr review of HCV test usage should be performed by the BTAC and
major laboratories to define indications for testing of blood donors and othermembers of the community, and ensure that tests of apporpriate sensitivityandspecificity are being used.
• (FDA recommendations)• a policy based on objective evidence should be established by the BTAC on
whether HCV marker-positive units of plasma may be used for manufacture ofany specified fractionated blood product.
26. The Journal of the American Blood Resources AssociationApril 23, 1992, FDA Memoranda Re: Testing Whole Blood for Anti-HCV
Supercedes the recommendations of November 1990. The FDA Blood ProductsAdvisory Committee recommends that all donations of Whole Blood and bloodcomponents intended for transfusion, and Source Plasma and Source Leukocytesintended for further manufacture, be screened by a licensed test for anti-HCV andthat no products repeatedly reactive for anti-HCV be used. The use of a multi-antigen test in the testing of Whole Blood and blood components for transfusionshould be implemented as soon as is feasible. Inventories of blood and bloodcomponents for transfusion that were collected before the multi-antigen testimplementation date should also be tested using the multi-antigen test if possible.Inventories of products intended for further manufacture and collected before thetest implementaiton date need not be tested retroactively.
27. NZ Med J 27 May 1992 Vol 105, No. 934:195-196
Patients with chronically disturbed liver funcion tests of uncertain cause are acommon clinical problem. We have found a prevalence of antibodies to HCV of26% in a sample of such patients. Although our cases were highly selected it wouldappear that GCV is a significant cause of chronic liver disease in New Zealand.
INQUIRY REPORT 64
28. Blood Vol 80 (July 15), 1992:540-543
It has been known since the early 1970s that haemophilia patients who frequentlyinfused coagulation factor concentrates manufactured from pooled plasma hadintermittently elevated liver aminotransferases [enzymes indicating inflammation ofliver]. These abnormalities were attributed mainly to NANBH. Cohort studies ofhaemophiliacs have shown that using the first-generation anti-HCV ELISA C100tests that at least 80% of haemophilia patients are positive. By Postransfusionfollow-up studies, seropositivity seems to indicate ongoing infection with the virusand not immunity (NEJM 321:1494, 1989).
Our study shows that with the increased diagnostic capability of the newer serologicassays for anti-HCV, an increased prevalence of 2.7% may be found in high-riskcohorts. However, the prevalence of HCV-infected partners of haemophilic indexpatients still remained low, indicating that HCV was not efficiently transmitted bythe heteroseuxal route and perhaps less effectively than other sexually transmissableviruses such as HIV.
29. NZ Med J , 23 Sept 1992 Vol 105, No 942: 376-377
The relative frequency of viral agents causing acute hepatitis was Epstein Barr virus52%, Cytomegalovirus 5%, HAV 15%, HBV 13% and HCV 15%.
30. NEJM Vol 327; Aug 6, 1992, No 6: 369-373
Of the 912 patients who received transfusions before donors were screened forsurrogate markers, 35 seroconverted to HCV, for a risk of 3.84 % per patient(0.45% per unit transfused). For the 976 patients who received transfusions afterOctober 1986 with blood screened for surrogate markers, the risk of serocnversionwas 1.54% per patient (0.19 % per unit transfused). For the 522 patients receivingtransfusions since the addition in May 1990 of screening for antibodies to HCV, therisk was 0.57% per patient (0.03% per unit transfused). The trend towarddecreasing risk with increasingly stringent screening of donors was statisticallysignificant (P <0.001). After we controlled for the method of donor screening, therisk of seroconversion was strongly associated (P <0.001) with the volume of bloodtransfused, but not with the use of particular blood components. We conclude thatthe incidence of PTH has decreased markedly since the implementation of donorscreening for surrogate markers and antibodies to HCV. The current risk of PTHCis about 3 per 10,000 units transfused.
31. THE LANCET Vol 340: August 1, 1992:305-306
We report a case of Hepatitis C (HCV) transmission via pasteurised plasma product.The has only received substitution of factor VII with Haemate P, and had no otherexposure. After thorough investigation we could exclude the transfusion of anyother plasma products to our patient. Thus, our case demonstrates that a FactorVIII concentrate, which has undergone viral inactivation through pasteurisation(60°C for 10 h in solution), may still occasionally transmit HCV. That this is a
INQUIRY REPORT 65
rare complication is illustrated by the fact that no other case of HCV transmissionhas been definitely connected to Haemate P over 10 years. Moreover, 7 of ourpatients, who have been treated only with Haemate P and who have receivedmaterial from at least one of the two positive batches half a year ago or more,remain anti-HCV negative. (Karolinska Hospital, Sweden)
32. NEJM Ed. 6 Aug 1992, Vol 327, No. 6: 419-421
Four key measures help keep the use of blood safe:1. all who prescribe blood should try to limit the frequency of homologous
transfusion by responding only to patients' physiologic needs and by usingalternatives such as autologous transfusion and intraoperative blood salvage.
2. the selection of safe donors provides the greatest safety.3. laboratory testing can identify the vast majority of donations from infected
persons.4. pooled plasma products routinely undergo viral-inactivation procedures.
Any contemplated additional measures to prevent transfusion-transmittedinfection must have demonstrable benefit. Preventive measures have thegreatest value when the threat to recipients is increasing, but for the infectiousagents of known concern to transfusion recipients in the United States the riskappears to be declining. Avoiding unnecessary use of blood and usingautologous transfusion aggressively are economical measures that will increasesafety further.
The chances of contracting a serious disease or dying from transfusion are nowmuch lower than with most therapeutic methods, and the objective of a zero-riskblood supply is virtually unachievable. Each step toward that goal absorbs moreresources that, if directed elsewhere, might have a much greater impact on thehealth of the public. Are continued efforts to reduce the risk of transfusion-transmitted infections commensurate with the risk itself, or with society'sperception of the risk? As has been persuasively argued elsewhere, there is noconsistent approach to dealing with this difficult question, but we should acceptit as our responsibility to educate the public about the real risks.
33NFJM Vol 327, 26 Nov 1992; No.22: 1601-1602
The second generation EIA detected I additional donor per 1000 tested who hadpotentially infectious HCV. Previous data indicate that 78 to 88 percent os suchdonors are likely to transmit HCV infection. The ability of the second-generation EIA to detect these potential HCV carriers, when combined with thealready low frequency of HCV transmission (before the introduction of thisimproved anti-HCV test, the risk was 1 per 3300 units) establishes that thecurrent risk of the transmissin of HCV by blood that is negative by the second-generation EIA is very low. The use of the second-generation EIA will prevent64% of the instances of HCV transmission that occur with the transfusion ofblood judged to be anti-HC V-negative on the basis of the first generation EIA.We estimate that the current risk of HCV invection per unit of blood transfusedranges from 1 in 2000 (0.05%) to 1 in 6000 (0.017%)
INQUIRY REPORT 66
APPENDIX 4
TRANSFUSION-TRANSMITTED INFECTION
1. Introduction
The support given by blood transfusion services to health care programmes isunique and essential for modern medical practice. They have played aconsiderable part in lowering maternal mortality during childbirth and in thedevelopment of cardiac surgery. The transfusion of blood or its components cancorrect many deficiencies (even if only temporarily) and in most cases this effectcan be acheived without any untoward effects.
It is theoretically possible that any infectious disease associated with thepresence of the causative organism in the bloodstream may be transmitted fromdonor to recipient by blood transfusion. Nevertheless disease transmission is notcommon, because in general bacteraemia or viraemia produces constitutionalsymptoms and blood donors do not give blood when they are ill.
Agents transmitted by blood transfusion often possess a combination of some orall of the following properties:
•They are present in the blood for long periods, sometimes in high titres.
•They have the ability to cause subclinical infections or only mildsymptoms.
•They have long incubation periods (sometimes years) before clinical signsappear.
•They may exist in a latent or carrier state, or both.
•They are stable in blood stored at 40C.
2. Organisms transmitted through blood/blood products
a) Bacteria
Bacterial complications of transfusion are rare because of the use of sterile,disposable collection sets and clean phlebotomy techniques. When they dooccur, however, they can rapidly be fatal, principally as a result ofendotoxic shock. Exogenous contaminants can be introduced into the bloodduring collection or (rarely) during processing, preparation and storage. Atpresent most blood components are prepared in closed systems; blood iscollected in multiple packs and the possibility of microbes entering the packsis negligible. Components prepared in an open system (such as washed cells
ENQUIRY REPORT 67
or filtered blood) need to be processed in sterile rooms and given a limited(24 hours) shelf life.
Common environmental contaminants that have been reported as causingserious (and often fatal) bacterial infections include pseudomonas,achromobacters, and coliforms (ie Gram negative bacteria that growpreferentially at 4-80C or at room termperature, but not at body temperatureof 37°C).
Reactions to the transfusion of bacterial contaminated blood usually developwithin minutes, with alarming signs and symptoms such as chills, rigors andfever.
Bacteria that may cause low grade or asymptomatic infections in the donor(such as Salmonella or Yersinia species) are sometimes an endogenoussource of contamination. Bacteria that do not grow well in blood stored at40C will grow rapidly in platelet concentrates that are routinely stored at 20-22°C. Fatal salmonella septicaemia has been caused by contaminatedplatelet concentrates.
b) Syphilis
Syphilis can be transmitted by fresh blood and platelets because the organismT. pallidum is only inactivated by refrigeration for 72 hours. It is nottransmitted by products fractionated from pooled plasma such as FactorVIII. The incubation period varies from four weeks to four and a halfmonths, the average being nine to ten weeks. It is only rarely transmitted bytransfusion and responds to treatment with antibiotics, usually a course ofbenzylpenicillin.
Screening for the antibody is required, and is usually by the cardiolipin assayor the (more specific) Tpallidum haemagglutination assay. In early primarysyphilis, at the height of infectivity, screening tests may be negative. Thedetection rate is low because those who have had the infection have usuallybeen treated. Donors with acute or latent infection are rare.
c) Malaria
Transmission of malaria is not uncommon in countries where malaria isendemic, but it may also occur in nontropical countries if former residents ofthe tropics are used as blood donors. Benign tertian (p. vivax) and malignanttertian (p. falciparwn) are rarely transmitted if the donor has been awayfrom a malarial country for two years, not suffered malaria during the twoyears, and has not been taking drugs in that time that suppress malaria.
INQUIRY REPORT 68
Plasmodium falciparum is the most dangerous of the human malarialparasites; the others are Plasmodium vivax, Plasmodium ovale andPlasmodium malariae. The organsims are restricted to red blood cells butmay contaminate components such as platelets. Freezing plasma will lyseany contaminated red cells, but malaria parasites can survive storage ofblood at 40C for at least a week. The incubation period is from one week toone month, but for the P malariae it may be several months.
In a malarial country the possibility of malarial transmission should beanticipated with every transfusion and a curative course of malarial therapyinstituted. In a non-malarial country the occurence of intermittent pyrexiaand rigors commencing six or more days after a transfusion should suggestthe possibilily of malarial infection and blood should be examined for thepresence of parasites.
d) Hepatitis B
The hepatitis B virus is plasma borne and easily transmitted by all bloodcomponents and any non-inactivated blood products. It is not transmitted bypasteurised albumin or immunoglobulins. The chance of transmission isenhanced when plasma is pooled for the manufacture of blood products.The incubation period ranges from two to six months but is usually aboutfour. Although it is extremely infectious when injected, the number oftransfusion transmitted cases has been drastically reduced by donorscreening. The few cases that do occur are caused by non-inactivatedcompounds. Inactivation of pooled plasma products (600C for 72 hours) hasproved effective in reducing the frequency of hepatitis B followingtransfusion.
Screening for hepatitis B surface antigen (HBsAg) is essential. Screening forthe delta agent is unnecessary as the delta agent depends on hepatitis B virusto provide its surface antigen. Screening for antibody to HBeAg can be usedto identify donors whose plasma is suitable for the preparation of hepatitis Bimmunoglobulin. Vaccine is available for protecting recipients of theproducts of pooled plasma who are negative for hepatitis B (for example,previously untreated haemophiliac patients) and for patients who needregular transfusions (for example, those with thalassaemia).
The incidence of post-transfusion hepatitis B has fallen significantly since theintroduction of sensitive screening tests for the hepatitis B surface antigen.Donor blood found to be antigen positive is not used for transfusion but canbe used to manufacture hepatitis B vaccine.
The risk of transmitting hepatitis B is much less with an individual unit ofblood than with blood products made from pools of plasma taken from alarge number of donors. Some products such as albumin solution are alsomade from large pools of plasma, but they are heated at 600C for 12 hours
ENQUIRY REPORT 69
during preparation so that any virus present is destroyed. Immunoglobulinsare not known to have transmitted hepatitis B as prepared in Australasia.Prothrombinex and Factor VIII Concentrate will withstand heating at 600Cfor 72 hours and this inactivates HIV and hepatitis B viruses.Immunoglobulin preparations appear to be free of risk, and this may be dueto their content of antibodies to hepatitis, as well as processing procedure.
e) Hepatitis A
Hepatitis A virus is the agent usually responsible for the disease knownclinically as 'infectious hepatitis', although it is now known that up to one-third of cases previously diagnosed as infectious hepatitis may have been dueto the hepatitis B virus. Infectious hepatitis due to the A virus has anincubation period of 20-40 days; the incubation period of the B virus is 40-160 days.
Hepatitis A is most commonly spread by the faecal-hand-mouth route or bycontaminated food and water rather than by blood transfusion. Presentopinion is that the hepatitis A virus is very infrequently the cause of post-transfusion hepatitis. This may be due to the fact that the virus is present inthe blood stream for only a short time, and the carrier state is a rareoccurence. Some products made from large pools of plasma may beoccasionally infected with the virus.
f) Non-A Non-B Hepatitis
Since the introduction of screening tests for hepatitis B surface antigen indonor blood it has become apparent that the majority of cases of post-transfusion hepatitis occuring are due to neither the A nor the B virus.
There may be at least two different viruses that transmit non-A, non-Bhepatitis. Recently tests have been developed in which cloned peptides canreact with antibody to the 'non-B' agent now called Hepatitis C. Most of thenon-A, non-B hepatitis that develops as a result of transfusion is nowthought to be due to Hepatitis C. Detail on Hepatitis C is coveredelsewhere.
g)HIV
HIV-1 was transmitted by transfusion before screening was introduced in1985 and before donors at high risk started excluding themselves fromgiving blood. HIV-2 occurs mainly in West Africa. Before screening wasintroduced, HIV had been transmitted by whole blood, red cell components,platelet concentrates and fresh frozen plasma. It can contaminate FactorVIII and Factor IX concentrates, but it is inactivated by specific methods of
INQUIRY REPORT 70
heat treatments and chemicals. It has not been transmitted by albumin orimmunoglobulins. The length of time before seroconversion is rarely longerthan three months.
New Zealand screens for HIV-1 and HIV-2 as the test kits used are sensitiveto both viruses.
Transmission of HIV by transfusion has been extremely rare since theintroduction of screening, but if it occurs in infants it leads more rapidly toserious disease than in adults. Only one donation from a seronegative donoris known to have transmitted HIV infection in the United Kingdom sincescreening started in 1985. No cases have been identified in Australasia since1985. The virus can be inactivated in blood products by treatment with heator chemicals, but blood and blood components (for example platelets) cannotbe treated in either of these ways. In New Zealand no donors with apositive HIV test have been detected since 1989.
h) Adult T Cell Leukaemia; Human T Cell Leukaemia Virus
Human T cell leukaemia virus (HTLV-I) is a retrovirus. The importance ofHTL V-Il is not clear. In the developed world it is associated withintravenous drug use and has been found in a few cases of hairy cellleukaemia. It is associated with white cells and not transmitted in plasma.The incubation period for adult T cell leukaemia is about 20 years, but eventhen only about I% of patients who are seropo . si I tiv- d develop the disease.HTLV-I can also (rarely) cause tropical spastic paraparesis, which seems tohave a shorter incubation period than adult T cell leukaemia. The infectionis endemic in the Caribbean, parts of Africa, and Japan where 3-5% of thepopulation are seropositive and where, before manadory screening,transmission by transfusion was quite common. It is also difficult todifferentiate between the antibodies to HTLV-I and HTLV-II unlessadvanced (and expensive) technology, such as the polymerase chain reaction,is available. No cases of HTLV I or II have yet been detected in NewZealand, either as patients or donors. Limited screening is at presentperformed on donors who have been living in endemic areas.
(i) Post-transfusion mononucleosis
The main features commence three to five weeks after a transfusion usuallyof fresh blood in large quantities. The cause is thought to be infection withcytomegalovirus or Epstein-Barr virus, the syndrome is usually benign.
INQUIRY REPORT 71
(j ) Cytomegalovirus
Cytomegalovirus (CMV) is a common viral infection and usually causes fewsymptoms in healthy adults. The virus is one of the herpes family andderives its name from the appearance of infected mononuclear cells whichare grossly enlarged with "cow's eye" inclusions in the nucleus. Apart frommononucleosis and occasional reports of mild liver damage followingtransfusion, CMV cannot be considered a harmful pathogen inimmunocompetent individuals. However, in neonates and inimmunosuppressed patients the virus may cause an overwhelming infectionand death may occur, usually from interstitial pneumonitis.
The incidence of antibody to CMV in the population increases with age toabout 75% in those over 60 years of age. The presence of CMV antibodiesindicates that the person has been exposed to the virus and in a majority ofsuch cases the virus is believed to remain in the infected individual in alatent form.
Blood transfusion has been shown to transmit CMV infection from CMVantibody positive donors to recipients, and the risk is greatest with leucocyteconcentrates. Removal of leucocytes from blood reduces the risk oftransfusion-transmitted CMV infection.
The incubation period is up to 12 weeks, and blood transfusion can causeprimary infection, reactivation of an endogenous latent infection, orreinfection with a different strain of the virus.
Because severe (and sometime fatal) cytomegalovirus disease may occur onlyafter transmission to immunosuppressed patients, selective screening ofdonors is sufficient to fulfil the demands of, in particular, recipients of bonemarrow transplants and low birthweight premature infants.
Granulocyte transfusions that are seropositive for cytomegalovirus areespecially likely to transmit the virus.
Components from which the white cells have been particularly or totallyremoved (for example, by special filters) have a reduced risk, and frozen redcells (from which the glycerol has been removed) and washed red cells tendnot to transmit cytomegalovirus because of their low white cell content.
(k) Parvovirus
Serum parvovirus is not usually pathogenic when transmitted by transfusion,although B19 can lead to an apl:stic crisis in a patient with chronichaemolytic anaemia (such as sickle cell anaemia) because of its inhibitoryeffect on red cell precursors. The risk of transmission by transfusion of non-pooled components is minute because there is no carrier state and the period
INQUIRY REPORT 72
of viraemia is short. The titre of virus during the period of viraemia,however, is high and infectious units of plasma can contaminate batches ofFactor VIII; over 90% of recipients of untreated Factor VIII are likely to beseropositive. Heat treatments of freeze dried Factor VIII at 800C for 72hours may inactivate the virus, although recent data indicates thatinactivation may not be complete.
/
U
INQUIRY REPORT 73
WH 460 IQ) 199289378
.I.N QUIRY into matters rel.at_:
inst..hesafetyo..loodproducts in New Zealand
89378W
460
QIINQ
1992
o Ab1Libre
Of Health
0
r
L
Department Of HealthTE TARI ORA
jj
4
