Castelfranco Veneto Radiopharmacy-Cyclotron Unit … 2014_Visentin.pdf · Castelfranco Veneto...

Castelfranco Veneto Radiopharmacy-Cyclotron Unit

Eclipse HP cyclotron

Roberta Visentin

CFV-Medipass Unit Manager

RDS111 and Eclipse RD/HP Cyclotron User Meeting, 2014 Imanova Ltd, London, UK

Medipass in short

• Medipass supplies turnkey advanced solutions of design, development and management for complex medical equipment in outsourcing to hospitals and private/ public healthcare facilities

• Medipass’ major focus is on innovative technologies, including:

- Diagnostic Imaging (RX, CT, MRI) - Nuclear Medicine (Radiopharmacy,

PET/CT) - Radiotherapy (Photons, Protons)

• Founded in 1996, in 2006 Medipass has become part of KOS-CIR Group

• In 2011 Medipass has activated a process of international development in UK (Medipass Healthcare) India (Clearmedi)

RDS111 and Eclipse RD/HP Cyclotron User Meeting 2014, Imanova Ltd, London, UK 2

Key activities

• Design of the layout and planning of the site that will host the service

• Acquisition of the technical equipment from primary manufacturers also as part of project financing initiatives

• Installation of the equipment, though this is performed by the supplier • Authorization and start-up of operation • Full-risk maintenance management • Life cycle management (i.e. periodical replacement / upgrade of medical

equipment) • Training of the client’s personnel

• Provision of specialized personnel (i.e. clinicians, radiopharm., physicists, …)

3 RDS111 and Eclipse RD/HP Cyclotron User Meeting 2014, Imanova Ltd, London, UK

Medipass has gained relevant experience in the management of advanced technologies applied to healthcare across Italy for both private and public hospitals

Italian Experiences

PET-CT (5 diagnostic units)

Radiopharmacy & Cyclotron (3 units)

M.E.S.

MRI, CT start-up

Radiation Therapy

Radiation Therapy start up

Diagnostic Outpatient Imaging Center

Lithotripsy

Ongoing bids


Medipass’ managed services operate for

5 PET-CT Diagnostic Units

3 Radiopharmacy with cyclotron

with a total of 74 dedicated professionals involved:

8 Nuc. Med. Physicians

4 Physicists

14 Diagn. Technicians

15 Radiopharmacists

12 Chem. Technicians

1 Nuclear Engineer

12 Admin. and Support

9 Hub staff & Logistic

Medipass professional contributions - Nuclear Medicine in Italy

to give assistance to approximately 22.000 PET patients yearly


UK active contracts

6

St. James Institute (Leeds)

MES (9 Linac and diagnostic equipment)

Belfast City Hosp. (Belfast)

MES (9 Linac and diagnostic equipment)


Valentis, Meerut

Linac Jindal, Hisar

Linac

Muni Seva Ashram,

Vadodara 2 Linacs

Radiant, Mysore

Linac

Sushrut, Mumbai -

PET CT

Hamdard, New Delhi

MRI, CT, Diagnostic Imaging

Paras, Patna

Linac, PET CT, Brachy

Sanjiban, Kolkata

Linac, MRI

Birla, Gwalior

Linac

Synergy, Indore

MRI, CT

Suretech, Nagpur -

Linac

Nanded Medical, Nanded

Linac

Ashwin, Coimbatore

Linac

Mission, Durgapur

Linac

Guru, Madurai

Linac

India Presence


Azienda ULSS 8 – Asolo

is a public Local Health Unit directly managing two hospitals

in the north east of Italy - one settled in Castelfranco Veneto -

and other healthcare and social service outlets

Castelfranco Veneto Hospital

in 1996 was the first public hospital in Italy

to have a Radiopharmacy-cyclotron unit

directed by Prof. G. Ferlin, one of EANM founders

Azienda ULSS 8 Asolo and Castelfranco Veneto Hospital

REGIONE VENETO


In 2001

medipass signed a collaboration agreement with


to distribute [F-18]fluoride produced by the RD-111

cyclotron installed in Castelfranco Veneto hospital

to other regional Nuclear Medicines

apporting production personnel and logistic coordination

REGIONE VENETO

Medipass agreements with Azienda ULSS 8 Asolo


REGIONE VENETO

In 2007

medipass signed a collaboration agreement with


for the

design and development of a new

radiopharmacy-cyclotron unit

and a managed service from 2009 to 2021

Medipass agreements with Azienda ULSS 8 Asolo


From the old site…


… to the new GMP-compliance site

ECLIPSE RD : two F-18, two C-11, one N-13, one O-15 targets


- September - October 2009 : RD/RD October 2009 : 1st UPGRADE BL2 - November 2009 – May 2011 : RD/HP May 2011 : 2nd UPGRADE BL1 - June 2011 – up to now : HP/HP

CASTELFRANCO ECLIPSE CONFIGURATION HISTORY


- 2nd UPGRADE : in order to satisfy the [F-18]FDG requests from satellite hospitals (discontinuation of own FDG preparation due to a «GMP like» new legislation coming into operation in July 2011),

need to overcome

• F-18 RD target reliability (yields, endurance) • low FDG yields using the first F-18 RD run • Ion Source instability

REASONS OF ECLIPSE UPGRADES


- 1st UPGRADE : acceptance tests yields lower than those expected as per technical references formally reported by Siemens in the public bid (F-18 targets: 1600 mCi instead of 2400 mCi)

REASONS OF 2nd UPGRADE : ION SOURCE INSTABILITY

31 rebuilts in 31 months, 10 PMs

Once close to 50 A_hrs, but usually no more than 25 A_hrs in between two rebuilts

IS REBUILTS AFTER 2nd UPGRADE


IS REBUILTS BEFORE 2nd UPGRADE

Maximum 21 A_hrs in between two rebuilts

ION SOURCE INSTABILITY : SOLVED

DECISIVE INTERVENTION ON DECEMBER 2013

SINCE DECEMBER 2013 ONLY TWO REBUILTS

FEBRUARY PM - 25.8 A_hrs MAY PM - 45.7 A_hrs

NEXT PM ON AUGUST

37.9 A_hrs

60/60 2 hrs dual beam IS current : 0.23- 0.28 A


ION SOURCE INSTABILITY : HIGHLIGTHED…

CLARIFICATION

NOT A QUESTION OF THE SINGLE PERSON, OF THE SINGLE TECHNICIAN OR ENGINEER CAME,

ALWAYS TRYING TO DO THEIR BEST FOR THE CUSTOMER

SIEMENS’ MAINTENANCE WAY OF FACING THE PROBLEM FOR DUE SUPPORT

LACK OF SIEMENS COORDINATION


3 TECHNICAL SUPPORT SOURCES

- RSC SUPPORT (since Sept. 2009)

- ITALIAN SUPPORT (since Aug. 2010)

- KNOXVILLE SUPPORT (7 I&S in 4 years)

ION SOURCE INSTABILITY : LACK OF SIEMENS COORDINATION


NOONE APPOINTED TO BE «SITE REFERENCE EXPERT» (knowing the story of the machine and in charge to coordinate interventions)

3 DIFFERENT TECHNICAL SUPPORTS

No evidence of

- COMMON PROCEDURES - COMMON DOCUMENTS

- REAL COMMUNICATION AMONG THEM

4 YEARS TO SOLVE THE PROBLEM

DESPITE THE 2nd UPGRADE

DESPITE THE INTENSE MONITORING PUT IN PLACE AND MAINTAINED BY THE CUSTOMER

WITH DATA ALWAYS AVAILABLE AND SHARED IN ORDER TO COLLABORATE WITH SIEMENS

FOR HELPING TO IDENTIFY THE SOLUTIONS ASAP AND FOR REDUCING THE DOWNTIME OF THE MACHINE

ION SOURCE INSTABILITY : LACK OF SIEMENS COORDINATION


3 DIFFERENT NATIONALITIES

- REGULATORY, eg. no common safety legislation

- TECHNICAL ISSUES, eg. different cylinder-regulator connections

THE RESULT

• HEAVY WASTE of TIME and RESOURCES/MATERIALS

• MISSMATCH with:

the TIMING and PERFORMANCE OBLIGATIONS

the (EXPENSIVE) TOP PLUS MAINTENANCE

CONTRACT

SIEMENS


THE RESULT

• HEAVY WASTE of TIME and RESOURCES+MATERIALS

• MISSMATCH with:

the TIMING and PERFORMANCE OBLIGATIONS toward

HOSPITALS (new projects delivery)

BUSINESS PLAN

MEDIPASS


DECEMBER 2010 started to realize that also BL2 F-18 HP target yields

were often under Siemens specs

F-18 RD RELIABILITY

THE UPGRADE TO HP/HP SHOULD HAVE SOLVED THE MATTER

JANUARY 2011 meeting in Milan to agree the second upgrade planned for May 2011

REASONS OF 2nd UPGRADE : F-18 RD TARGET RELIABILITY


FEBRUARY - MARCH 2011 noted to Siemens that HP F-18 target yields were lowering day by day, especially considering long runs, with a marked “first run – first effect”

2011

D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A

FEBRUARY – APRIL 2011

interventions on BL2 F-18 HP target

February 2011 : installation of a target body discarded in October 2009

March 2011 : installation of the target body removed on February

April 2011 : new target body and

new cleaning procedure

2011

F-18 HP TARGETS : OPEN QUESTION



F-18 HP TARGETS: OPEN QUESTION

Procedure A: from November 2009 to April 2011 chloroform/acetone/methanol/water Procedure B: from April 2011 to May 2011 diluted nitric acid

DIFFERENT CLEANING PROCEDURES


2011


MAY 2011

BL1 UPGRADE

and new cleaning procedure

2011





Procedure A: from November 2009 to April 2011 chloroform/acetone/methanol/water Procedure B: from April 2011 to May 2011 diluted nitric acid Procedure C: from May 2011 to February 2012 concentrate nitric acid / concentrate hydrogen peroxide



2011



HP TARGETS FROM THE 2nd UPGRADE TO DECEMBER 2011

F-18 target saturation yields (dose calibrator) :

- in blue BL1 target installed on May 2011 cleaned with procedure C

- in red 4 different targets installed/reistalled on BL2 cleaned with procedure C

2011


2011



“nitric acid and hydrogen peroxide treatment on F-18 targets has been useful to avoid the problem of “long run [F-18]fluoride low yields”, but in the case of “old targets” (target previously used and then treated with the mixture) the [F-18]fluoride yields start to decrease again in a more or less short period. (…) Like if, for “old target”, the “passivation” due to oxidant treatment would easily degrade over time leaving impurities responsible of [F-18]fluoride yield decrease to diffuse to the outer surface.”

DECEMBER 2011: note to Siemens


2011 2011



“The matter is that from six months (after the cyclotron up-grade),

when we started to produce FDG with [F-18]fluoride from day by day longer 60/60 uAmps dual beams,

we are suffering of a high dispersion on FDG yields

(in the range 18-65%).

Moreover, the FDG yields worsened from July up to now (….)

We investigated the possible reasons of such trend, evaluating synthesis modules, transfer lines, starting materials, gases and

everything else involved in FDG syntheses.”



2011 2011



“However, if we can be confident that the second treatment with the

“etchant” will guarantee an improvement in [F-18]fluoride yields,

you can understand that we are really and really afraid about how the tantalum of all the targets we

are using can affect the FDG yields.

You would agree with us that for a cyclotron it is important to give not only “on spec” [F-18]fluoride yields,

but “on spec” yields of high quality [F-18]fluoride”



2011 2011



FEBRUARY 2012 : NEW TARGET FOR BL2 AND A NEW CLEANING PROCEDURE

Procedure A: from November 2009 to April 2011 chloroform/acetone/methanol/water Procedure B: from April 2011 to May 2011 diluted nitric acid Procedure C: from May 2011 to February 2012 concentrate nitric acid / concentrate hydrogen peroxide

Procedure D: from February 2012 chloroform/acetone/methanol/water and 8 hr oven backing at 120° C


2012


2011



F-18 target saturation yields : in blue BL1 target installed on May 2011 ; in red BL2 target installed on February 2012

HP TARGETS FROM FEBRUARY 2012 TO JUNE 2012


2012 2011


JUNE 2012: medipass CFV Radiopharmacy & Cyclotron Unit – June 2012 report

1. INTRODUCTION

2. MATERIALS AND METHODS

2.1. Modules and hot cells

2.2. Connections among cyclotron, modules and hot cells

2.3. FDG synthesis

2.4. [F-18]Fluoride: delivery from cyclotron to modules and activity measurements

2.5. [F-18]Fluoride: yields and [F-18]fluoride vial GM calibration

2.6. [F-18]Fluoride: loss of volume during delivery

2.7. FDG: delivery from modules to hot cell “B” and vial dispensing

2.8. FDG: yields and FDG collecting vial GM calibration

2.9. Corrected FDG yields

2.10. Activity balance

2.11. Target maintenances and substitutions in the last year

2.12. Target wash-dry procedure

2.13. Synthesis module maintenance

2.14. Dose calibrator constancy and linearity

2.15. [F-18]fluoride daily production plans

2.16. Discarded data

3. RESULTS AND DISCUSSION

3.1. Saturation target yields from July 2011 to July 2012

3.2. Target yields: maintenances, target substitutions and different cleaning procedures

3.3. FDG yields from July 2011 to July 2012

3.4. FDG activity balance

4. CONCLUSIONS

4.1. Target yields

4.2. FDG yields





4. CONCLUSIONS 4.1 Target yields

“From April 2011 to February 2012, based on data progressively collected, three different new cleaning procedures have been tested, confirming that a problem related to target quality really existed and needed to be solved. Target yield data also indicate that probably the last version of cleaning procedure, involving a final backing step and in use from February, can be useful to increase the goodness of targets and their performances. Moreover, the mismatch between BL1 and BL2 target behaviours is almost cancelled: since rebuilt with the backing procedure the two targets show matching yield trends. On the other hand, the trend of BL1 target yields slowly decreased in one year, and both the targets are at the moment under Siemens specs. This in contrast with other Siemens site experiences, where the same targets are employed from seven-nine years giving always very consistent yields and purity at 60 uA, although rebuilt by using the “old” cleaning procedure with chloroform/acetone/methanol/water”




4. CONCLUSIONS 4.2 FDG yields

“(…) impurities coming from targets interfered with nucleofilic substitution during FDG syntheses, giving raise in 2011 to really low FDG yields and to the downward yield trend observed, the backing step recently adopted is more effective in passivating the target than chemical oxidizing treatments, perhaps thanks to a deeper action. On the other side, dispersion on FDG yields is still an open question, that prompt us to consider again our previous comments about “target passivation which can degrade leaving impurities to diffuse from the outer surface””


2012


2011


NOVEMBER 2012 :

TWO NEW TARGETS FROM A DIFFERENT TANTALUM BAR LOT


2012


2011


BL2 target : constantly below Siemens specifications from December 21st 2012

BL1 target : almost constantly below Siemens specifications after the PM made on May 2013

However, FDG yield dispersion was markedly reduced

F-18 target saturation yields : in blue BL1 target; in red BL2 target

HP TARGETS FROM NOVEMBER 2012 TO AUGUST 2013



AUGUST 2013 :

A NEW ATTEMPT TO SOLVE THE PROBLEM

WORKING ON O-18 WATER LOADING LINE


2012


2011 2013


F-18 target saturation yields : in blue BL1 target; in red BL2 target

HP TARGETS FROM NOVEMBER 2012 UP TO NOW


BL2 target : constantly below Siemens specifications

BL1 target : constantly below Siemens specifications

However, FDG yield dispersion still reduced


THE RECENT «MIRACLE» OF BL2 TARGET

ON MAY 6th BL2 TARGET BLEW UP JUST FOUR WORKING DAYS BEFORE THE PM

2014


2012


2011 2013



BL2 F-18 target after the maintenance made on May 7th 2014 because blown up reached an yield 13% higher if compared to the average yield from August, without cleaning because of the imminent PM BL2 F-18 target after the quarterly PM made on May 12th 2014 reached an average yield 19% higher if compared to the average yield from August




• A TARGET NEVER IN SPEC FOR 18 MONTHS • NOT IN SPEC NEITHER AFTER PMs

• IN SPEC WITHOUT CLEANING AND BACKING • IN SPEC WITHOUT ANY ATTEMPTS TO IMPROVE YIELDS

What done during May 7th intervention :

- CHANGE OF HAVAR WINDOW

- CHANGE OF O-RINGS - CHANGE OF GRID (old spare grid)

- CHANGE OF STRIPPING FOILS


What done during May 12th PM :

- CHANGE OF HAVAR WINDOW - CHANGE OF O-RINGS

- CHANGE OF GRID (new grid)


The day in which we moved from stripping foil 1 to 2 (July 7th), BL2 F-18 target yields decreased again, and now it is under Siemens specs, althought we moved to foil 1 again

THE END OF THE «MIRACLE»



Tantalum Targets Siemens departed from Silver to Tantalum target bodies in 2002 with great benefits:

Fewer metal ions in solution

All detected products are from Havar foil.

Less than minimum detectable activity in last two purification cartridges and final product.

Number of runs between rebuilds has increased

Silver targets typically required rebuilding at 3000 µA-hr week intervals.

Tantalum targets operate well above 10,000 µA-hr before rebuilds are necessary.

Beam on target has increased as well

Silver target was typically operated at 55 µA.

Tantalum operates at 60 µA comfortably, with room to grow.

Saturation yield increased 10%, FDG yield increased 10% and standard deviations improved.

Key Benefits Reduced cost

Lower operating expenses

Enhanced reliability

http://www.medical.siemens.com/webapp/wcs/stores/servlet/SMGenericDisplay~q_catalogId~e_-1~a_langId~e_-1~a_pageId~e_129015~a_storeId~e_10001.htm

STILL A CHANCE TO EXPERIENCE HP TARGET KEY BENEFITS

HOWEVER, IT CANNOT BE JUST AN ILLUSION


Note : 10,000 µA-hr = 166 hrs = 83 runs 120’ = 4 months

Note






WHAT DONE SINCE 2012

CHANGED TARGET POSITION from pos. 1 to pos. 2 SWAPPED TARGETS FIXED TGT COOLING

MADE PAPER BURN TESTS CHANGED O-18 WATER RESERVOIRS

CHANGED O-18 WATER LOADING LINES CHANGED O-18 WATER LOADING VOLUME

CHANGED DELIVERY LINES (PTFE-PEEK) CHANGED O-16 RINSE WATER

CHANGED TANTALUM… … WHAT ELSE?

(shape similar to a Pandora’s box…)



WHAT ABOUT NEXT ANNUAL PM ON AUGUST 2014 ?

WHAT ABOUT AFTER 42 MONTHS ?



2014 2012


2011 2013

AIM OF THIS KIND OF MEETINGS

Complaining by itself in useless and collaboration is foundamental

to accelerate troubleshooting

Meetings like this should be serioulsly promoted by Siemens because the main aim of all the customers

is for sure to contribute to rapid problem answers and to give suggestions for improving solutions,

in spite of their different needs

However,


ACTUAL SITUATION

SINCE 2011

• Medipass is still waiting concrete answers

• Medipass is still wasting concrete resources and opportunities

• Medipass is still willing itself to go on for satisfying Regione Veneto requests as per formal CFV Radiopharmacy-cyclotron unit Regional role

And, considering the last point, we can do it, because in 5 years we gained the experience for dealing with the machine in a “easygoing” way However, specifications are specifications, and we cannot compromise



part of the best

medipass advanced healthcare services

www.medipass.it www.medipasshealthcare.com

a Group company

medipass s.r.l. Via Ilio Barontini, 20 40138 Bologna - ITALY tel. +39 051-42.93.011 e-mail: [email protected]

THANK YOU


http://www.medipass.it/

http://medipasshealthcare.com/

mailto:[email protected]

Castelfranco Veneto Radiopharmacy-Cyclotron Unit … 2014_Visentin.pdf · Castelfranco Veneto...

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