12 th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV –...
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12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 1
FDA perspective on “Where are we?
Where can we go?”
12th Annual FDA & the Changing Paradigm for Blood Regulation16 January 2009 -- Las Vegas, NV
Gilliam B. Conley Director, Division of Inspections & SurveillanceFDA, Center for Biologics Evaluation & Research Office of Compliance & Biologics Quality
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 2
Introduction
We will discussFDA inspection dataFatalities reported to FDABiological Product Deviation Reports Where (can) should we go?
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 3
FY-2008 Inspections Conducted
Blood Bank – Level 1 679
Blood Bank – Level 2 316
Blood Bank – Total: ~ 1,000
Source Plasma – Level 1 89
Source Plasma – Level 2 60
Source Plasma – Pre-license/Pre-approval 19
Source Plasma – Total: 165
note: totals may not match because some inspections are for products in multiple categories
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 4
Top 10 Biologics ObservationsFY-2008 (Oct. ’07 through Sept. ’08)
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 5
Top 10 Blood & Blood Component ObservationsFY-2008 (Oct. ’07 through Sept. ’08)
Cite ID Count 21 CFR… Text
#1 76 116 606.100(b) Written standard operating procedures including all steps to be followed in the [collection] [processing] [compatibility testing] [storage] [distribution] of blood and blood components for [homologous transfusion] [autologous transfusion] [further manufacturing purposes] are not always [maintained] [followed] [maintained on the premises]. Specifically, ***
#2 98 31 606.100(c) Failure to [perform a thorough investigation] [make a record of the conclusions and follow-up] of [an unexplained discrepancy] [a failure of a lot or unit to meet any of its specifications]. Specifically,***
#3 9225 29 606.171 Failure to submit a biological product deviation report [within 45 days from the date you acquired information suggesting that a reportable event occurred]. Specifically, ***
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 6
Top 10 Blood & Blood Component Observations FY-2008 (Oct. ’07 through Sept. ’08) - continued
Cite ID Count 21 CFR… Text (abbreviated)
#4 31 26 606.20(b) Personnel…to assure competent performance of their assigned functions, and to ensure that the final product has the safety, purity, potency, identity and effectiveness it purports or is represented to possess.
#5 4425 23 606.60(a) Equipment…to assure that it performs in the manner for which it was designed.
#6 160 19 606.160(a)(1) Records…so as to provide a complete history of work performed.
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 7
Top 10 Blood & Blood Component Observations FY-2008 (Oct. ’07 through Sept. ’08) - continued
Cite ID Count 21 CFR… Text (abbreviated)
#7 154 17 606.160(a)(1) Records concurrently maintained with the performance of each significant step…
#8 67 16 606.65(e) Use supplies and reagents in a manner consistent with instructions provided by the manufacturer
#9 155 15 606.160(b) Failure to maintain…records
#10 159 10 606.160(a)(1) Records…
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 8
Inspection Classification – FY-2008
Blood Banks Source Plasma
NAI 743 107
VAI 243 50
OAI 13 1
Note: These numbers represent a snapshot in time from our inspections database. Because of the further routine review following an investigator’s initial recommendation for an OAI inspection decision, the year-end actual numbers are fewer than the 14 reported here.
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 9
Regulatory Actions – FY-2008
Warning Letters> 1 – Source Plasma> 3 – transfusion services or blood centers
Adverse Determination Letters> 1 – issued under consent decree
covered multiple facility inspections
Find on the web:WL - http://www.fda.gov/foi/warning.htmADL - http://www.fda.gov/ora/frequent/default.htm
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 10
Adverse ReactionsRegulatory Requirements, Guidance, Reports
Requirement 21 CFR 606.170(a) Requires Records & Investigation
Requirement 21 CFR 606.170(b) Requires reporting to FDA “a complication … confirmed to be fatal … as soon as possible”
Requirement 21 CFR 640.73 – re: Source Plasma Requires reporting “a fatal reaction which, in any way, may be associated with plasmapheresis…”
Guidance http://www.fda.gov/cber/gdlns/bldfatal.htm Sept., 2003 Final Guidance
Reports & FDA contacts
http://www.fda.gov/cber/transfusion.htm 2nd annual report was posted in mid-Nov.
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 11
Transfusion-related fatalities
Complication FY ’05 FY ’06 FY’ 07 TotalTRALI 29 35 34 98 (55%)HTR (non-ABO) 16 9 2 27 (15%)Microbial Infection 8 7 6 21 (12%)TACO 1 8 5 14 (8%)HTR (ABO) 6 3 3 12 (7%)Anaphylaxis 0 1 2 3 (2%)Other 2 0 0 2 (1%)
Totals: 62 63 52 177
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 12
Reports of TRALI by implicated Blood Product
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 13
Hemolytic Transfusion Rx.
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 14
Microbial Infection by Implicated Organism
Organism FY ’05 FY ’06 FY ’07 Total
Babesia microti 0 2 3 5 (24%)
Staphylococcus aureus 3 0 1 4 (19%)
Escherichia coli 0 3 0 3 (14%)
Serratia marcescens 2 0 0 2 (10%)
Staphylococcus lugdunensis 1 0 0 1 (05%)
Staphylococcus epidermidis 1 0 0 1 (05%)
Eubacterium limosum 1 0 0 1 (05%)
Morganella morganii 0 1 0 1 (05%)
Yersinia enterocolitica 0 1 0 1 (05%)
Streptococcus dysgalactiae 0 0 1 1 (05%)
Klebsiella oxytoca 0 0 1 1 (05%)
Total: 8 7 6 21
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 15
Biological Product Deviation ReportsRegulatory Requirements, Guidance, Reports
Requirement 21 CFR 600.14
§ 606.171 Report any event … may affect safety, purity, or potency of distributed product
Guidance http://www.fda.gov/cber/gdlns/devbld.htm Oct., 2006 – Final Guidance
Reports & FDA contacts
http://www.fda.gov/cber/biodev/reports.htm 5 years of annual reports are available
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 16
BPDR for Blood & Blood ComponentsManufacturing System FY-2003 FY-2004 FY-2005 FY-2006 FY-2007
Donor Suitability 32,453 28,952 29,148 29,067 32,280
Post Donation Info 30,331 26,854 27,452 27,427 30,033
Donor Screening 2,030 2,007 1,628 1,548 2,027
Donor Deferral 92 91 68 92 220
QC & Distribution 2,706 3,740 3,934 4,134 4,555
Labeling 2,429 2,415 2,405 2,199 2,309
Laboratory Testing 1,126 1,122 981 1,013 1,163
Routine Testing 1,037 1,027 912 945 1,103
Viral Testing 89 95 69 66 60
Collection 1,133 851 972 718 704
Component Preparation 371 368 407 401 419
Miscellaneous 288 382 525 658 1,400
Total: 40,506 37,830 38,372 38,188 42,830
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 17
0
5,000
10,000
15,000
20,000
25,000
30,000
35,000
# Reports
FY03 FY04 FY05 FY06 FY07
Reports Received
BPD Reports
PDIDSDDQCLARTVTBCCPMI
Biological Product Deviation Reporting
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 18
Total BPD Reports
315003200032500330003350034000345003500035500
FY03 FY04 FY05 FY06 FY07
Reports Received
# R
eport
sBlood Establishments
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 19
Post Donation Information Reports
150016001700180019002000210022002300Oct
Nov
Dec Jan
Feb
Mar
Apr
May Jun
Jul
Aug
Sep
Reports Received FY07
# R
epor
tsBlood Establishments
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 20
Post Donation Information Reports
0100200300400500600700800
Oct
Nov
Dec Jan
Feb
Mar
Apr
May Jun
Jul
Aug Sep
Reports Received FY07
# R
epor
ts
Malaria CJD travel Tattoo/Piercing
Blood Establishments
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 21
Total BPD Reports
010002000300040005000600070008000
FY03 FY04 FY05 FY06 FY07
Reports Received
# R
eport
sPlasma Establishments
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 22
Post Donation Information Reports
0100200300400500600700800Oct
Nov
Dec Jan
Feb
Mar
Apr
May Jun
Jul
Aug
Sep
Reports Received FY07
# R
epor
tsPlasma Establishments
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 23
Post Donation Information Reports
04080120160200240280320360
Reports Received FY07
# R
eport
s
Tattoo Piercing Incarceration
Plasma Establishments
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 24
Donors who subsequently test positive for viral marker
FY-’05 FY-’06 FY-’07
Lookback; Subsequent
unit confirmed pos (MI-02) – total:
495 608 1,367
HIV (MI-02-02) 92 99 210
HBV (MI-02-03) 50 90 344
HCV (MI-02-04) 333 372 708From FY-2007 annual BPDR summary reportBlood Safety Team (BST) reviewed rising numbers of reportsBST requested additional information from several manufacturersRise appears to be the result of
>Altered reporting patterns after the October, 2006 final Guidance published Biological Product Deviation Reporting for Blood and Plasma Establishments >Rising numbers of collections – especially in Source Plasma centers
BST will continue to monitor these seroconversion rates
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 25
Where (can) should we go?We will continue to gather informationWe will continue to report information
(web based information, public presentations, …)
We are interested in learning:> How do you use FDA’s posted data?
• Analyze with own data?• Institute quality change?
> Which FDA-posted data is most useful?> What are your success stories?
Please find a way to share with others
12th Annual FDA & the Changing Paradigm for Blood Regulation – 01/16/2009 – Las Vegas, NV – Gilliam B. Conley 26
Questions
Please join in the Q & A session
at the conclusion
of this morning’s session.