Regulatory Open Forum

We are a contract service provider including formulation development, clinical trial manufacturing and lab testing services.  I would like comment on a scenario whereby a pharma company client has contracts with the service provider to receive their bulk solution product and contract sterile fill the product into vials for Phase 1 and 2 clinical trials.  The only finished product testing the contractor is being asked to do is final sterility.  Samples are pulled from the lot and sent to the contract provider for all other finished product testing.  In our case, it is not uncommon to have a scenario whereby we may not do all testing.  In fact, multiple labs may be involved.  No problem.  The usual is that we have the finished product spec and manufacturing quality receives CoAs of results of all testing per the spec and thus can sign off GMP release for shipping with data showing product meets spec (GMP).  But imagine a scenario whereby the client does not want to share finished product spec or finished product test results (I can't help but wonder why not), but to have the contractor sign off on batch release based only on batch record review that manufacturing was correct and finished product sterility testing passes.  It is my opinion this is not GMP and if the contract giver wants the product shipped, it must done under quarantine and not GMP released.  But imagine the contract giver feeling shipping under quarantine means there is something wrong with the product rather than simply allowing shipment, under strict controls, for additional processing, testing, etc. (although it is my opinion shipping under quarantine should be avoided whenever possible).   In these days of Q Agreements and increased outsourcing, such discussions about a contract giver dictating what the contract receiver is to do and believing "It's our product and you are simply a contractor," have become more and more commonplace.  Whereas I believe there is shared responsibility and seek a "partnership" in assuring GMP compliance and a safe and pure product for the clinic.   Any comments? 

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Christopher Smith, CQE, RAC
Vice President, Corp QA & RA
AAIPharma Services Corp.
Wilmington, NC 28405, USA
christopher.smith@aaipharma.com
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We contract out the kind of services you describe and ultimately we have final responsibility for product release as specificed in our Quality Agreement.  We review batch records after CMO Quality Assurance review and we also conduct the product potency assay in our cGMP-compliant analytical laboratory.  We provide the potency data to the CMO who incorporates it into their CoA along with other test results conducted by their labs and external contract labs.  I would agree with your asessment that, if your customer doesn't share final test results with you, and if you have not had an opportunity to audit their procedures, you should ship material under quarantine (which, as you suggest, is far from ideal).  Of course, how and where the product finally is removed from quarantine is an open issue which I can't address based on the scenario you describe.  I like your idea of a 'partnership' which is how we operate with our CMOs.
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John Parker PhD
Senior Director RA and Quality Systems
Vaccinex, Inc.
Rochester NY
United States
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Original Message:
Sent: 05-26-2011 10:15
From: Christopher Smith
Subject: Releasing Clinical Trial Materials

We are a contract service provider including formulation development, clinical trial manufacturing and lab testing services.  I would like comment on a scenario whereby a pharma company client has contracts with the service provider to receive their bulk solution product and contract sterile fill the product into vials for Phase 1 and 2 clinical trials.  The only finished product testing the contractor is being asked to do is final sterility.  Samples are pulled from the lot and sent to the contract provider for all other finished product testing.  In our case, it is not uncommon to have a scenario whereby we may not do all testing.  In fact, multiple labs may be involved.  No problem.  The usual is that we have the finished product spec and manufacturing quality receives CoAs of results of all testing per the spec and thus can sign off GMP release for shipping with data showing product meets spec (GMP).  But imagine a scenario whereby the client does not want to share finished product spec or finished product test results (I can't help but wonder why not), but to have the contractor sign off on batch release based only on batch record review that manufacturing was correct and finished product sterility testing passes.  It is my opinion this is not GMP and if the contract giver wants the product shipped, it must done under quarantine and not GMP released.  But imagine the contract giver feeling shipping under quarantine means there is something wrong with the product rather than simply allowing shipment, under strict controls, for additional processing, testing, etc. (although it is my opinion shipping under quarantine should be avoided whenever possible).   In these days of Q Agreements and increased outsourcing, such discussions about a contract giver dictating what the contract receiver is to do and believing "It's our product and you are simply a contractor," have become more and more commonplace.  Whereas I believe there is shared responsibility and seek a "partnership" in assuring GMP compliance and a safe and pure product for the clinic.   Any comments? 

-------------------------------------------
Christopher Smith, CQE, RAC
Vice President, Corp QA & RA
AAIPharma Services Corp.
Wilmington, NC 28405, USA
christopher.smith@aaipharma.com
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Christopher,

I have encountered scenarios that allude to what you have described. What I have found useful in discussions regarding potential quarantine occurrences in this regard are the use of process flow diagrams and procedures showing complete ownership and transfer of ownership between parties so everyone can visualize their responsibilities in the process. This method worked very well for me in another company where a biologic was processed in our plant for a customer, and then had to be sent out for sterilization and additional testing at several contract labs managed by the customer. This entire process was considered under quarantine until such time as final COAs, test data and QA release were received from the customer. Our documents were then updated and the quarantine was resolved with this documentation. FDA never took issue with this well defined and documented process approach.

 
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Rodger Brown
VP, RA & QA
Neoprobe Corp
Dublin OH
United States
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Original Message:
Sent: 05-27-2011 10:03
From: John Parker
Subject: Releasing Clinical Trial Materials


We contract out the kind of services you describe and ultimately we have final responsibility for product release as specificed in our Quality Agreement.  We review batch records after CMO Quality Assurance review and we also conduct the product potency assay in our cGMP-compliant analytical laboratory.  We provide the potency data to the CMO who incorporates it into their CoA along with other test results conducted by their labs and external contract labs.  I would agree with your asessment that, if your customer doesn't share final test results with you, and if you have not had an opportunity to audit their procedures, you should ship material under quarantine (which, as you suggest, is far from ideal).  Of course, how and where the product finally is removed from quarantine is an open issue which I can't address based on the scenario you describe.  I like your idea of a 'partnership' which is how we operate with our CMOs.
-------------------------------------------
John Parker PhD
Senior Director RA and Quality Systems
Vaccinex, Inc.
Rochester NY
United States
-------------------------------------------






Original Message:
Sent: 05-26-2011 10:15
From: Christopher Smith
Subject: Releasing Clinical Trial Materials

We are a contract service provider including formulation development, clinical trial manufacturing and lab testing services.  I would like comment on a scenario whereby a pharma company client has contracts with the service provider to receive their bulk solution product and contract sterile fill the product into vials for Phase 1 and 2 clinical trials.  The only finished product testing the contractor is being asked to do is final sterility.  Samples are pulled from the lot and sent to the contract provider for all other finished product testing.  In our case, it is not uncommon to have a scenario whereby we may not do all testing.  In fact, multiple labs may be involved.  No problem.  The usual is that we have the finished product spec and manufacturing quality receives CoAs of results of all testing per the spec and thus can sign off GMP release for shipping with data showing product meets spec (GMP).  But imagine a scenario whereby the client does not want to share finished product spec or finished product test results (I can't help but wonder why not), but to have the contractor sign off on batch release based only on batch record review that manufacturing was correct and finished product sterility testing passes.  It is my opinion this is not GMP and if the contract giver wants the product shipped, it must done under quarantine and not GMP released.  But imagine the contract giver feeling shipping under quarantine means there is something wrong with the product rather than simply allowing shipment, under strict controls, for additional processing, testing, etc. (although it is my opinion shipping under quarantine should be avoided whenever possible).   In these days of Q Agreements and increased outsourcing, such discussions about a contract giver dictating what the contract receiver is to do and believing "It's our product and you are simply a contractor," have become more and more commonplace.  Whereas I believe there is shared responsibility and seek a "partnership" in assuring GMP compliance and a safe and pure product for the clinic.   Any comments? 

-------------------------------------------
Christopher Smith, CQE, RAC
Vice President, Corp QA & RA
AAIPharma Services Corp.
Wilmington, NC 28405, USA
christopher.smith@aaipharma.com
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Christopher

Your scenario could well happen and I think it is a splendid example why you should cover any such possibilities in a quality agreement as is now mandated in Europe (see Chapter 7 of EudraLex Volume 4).
In there the precise roles and responsibilities need describing. Whatever will be agreed, the licence holder (contract giver) remains responsible for product quality versus the authorities.
Siegfried

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Siegfried Schmitt
PAREXEL
Braintree, Essex
United Kingdom
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Original Message:
Sent: 05-26-2011 10:15
From: Christopher Smith
Subject: Releasing Clinical Trial Materials

We are a contract service provider including formulation development, clinical trial manufacturing and lab testing services.  I would like comment on a scenario whereby a pharma company client has contracts with the service provider to receive their bulk solution product and contract sterile fill the product into vials for Phase 1 and 2 clinical trials.  The only finished product testing the contractor is being asked to do is final sterility.  Samples are pulled from the lot and sent to the contract provider for all other finished product testing.  In our case, it is not uncommon to have a scenario whereby we may not do all testing.  In fact, multiple labs may be involved.  No problem.  The usual is that we have the finished product spec and manufacturing quality receives CoAs of results of all testing per the spec and thus can sign off GMP release for shipping with data showing product meets spec (GMP).  But imagine a scenario whereby the client does not want to share finished product spec or finished product test results (I can't help but wonder why not), but to have the contractor sign off on batch release based only on batch record review that manufacturing was correct and finished product sterility testing passes.  It is my opinion this is not GMP and if the contract giver wants the product shipped, it must done under quarantine and not GMP released.  But imagine the contract giver feeling shipping under quarantine means there is something wrong with the product rather than simply allowing shipment, under strict controls, for additional processing, testing, etc. (although it is my opinion shipping under quarantine should be avoided whenever possible).   In these days of Q Agreements and increased outsourcing, such discussions about a contract giver dictating what the contract receiver is to do and believing "It's our product and you are simply a contractor," have become more and more commonplace.  Whereas I believe there is shared responsibility and seek a "partnership" in assuring GMP compliance and a safe and pure product for the clinic.   Any comments? 

-------------------------------------------
Christopher Smith, CQE, RAC
Vice President, Corp QA & RA
AAIPharma Services Corp.
Wilmington, NC 28405, USA
christopher.smith@aaipharma.com
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