Regulatory Open Forum

A few years ago, at my previous company, we were noticing a trend of increasing concern from FDA re. extractables/leachables for a new application or a new manufacturing facility, and particularly an expectation that some discussion of extractables/leachables be present in the BLA or sBLA dossier.  Not a lot of detail, but at least a summary of what studies may have been done, risk assessments, etc.

Now, in my present company, we in RA are getting push-back, particularly from our European colleagues, on the necessity of including such information in the dossier.  They insist it is an inspection issue.  The concern is all around the timing of when the reports need to be approved - if it's going in the regulatory filing, it needs to be done a few months sooner.

I'm wondering if anyone has received feedback from FDA specifically requesting this information during regulatory review of the dossier, not only at inspection.

Thanks,
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Rachel Thornton
Associate Director
UCB
Smyrna GA
United States
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I should clarify that I'm not talking about the E/L for the primary packaging, but for all the product-contact materials used in the process.  I know in the past (> 5 yrs ago) such discussion was not included in our filings, but it is our (RA-CMC's) sense that at least a summary discussion of the issue is expected in the filing, esp. for biologics.  But some concrete examples would be helpful.

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Rachel Thornton
Associate Director
UCB
Smyrna GA
United States
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Original Message:
Sent: 10-25-2013 10:47
From: Rachel Thornton
Subject: extractables/leachables discussion in BLA/sBLA

A few years ago, at my previous company, we were noticing a trend of increasing concern from FDA re. extractables/leachables for a new application or a new manufacturing facility, and particularly an expectation that some discussion of extractables/leachables be present in the BLA or sBLA dossier.  Not a lot of detail, but at least a summary of what studies may have been done, risk assessments, etc.

Now, in my present company, we in RA are getting push-back, particularly from our European colleagues, on the necessity of including such information in the dossier.  They insist it is an inspection issue.  The concern is all around the timing of when the reports need to be approved - if it's going in the regulatory filing, it needs to be done a few months sooner.

I'm wondering if anyone has received feedback from FDA specifically requesting this information during regulatory review of the dossier, not only at inspection.

Thanks,
-------------------------------------------
Rachel Thornton
Associate Director
UCB
Smyrna GA
United States
-------------------------------------------

Yes, leachables and extractables testing is required by the FDA.  Here is the link to the ANDA checklist ANDA Checklist for Completeness and Acceptability. which is updated quarterly and where the requirement can be found.  Although it states for plastics, be aware that stoppers are included in this category.  USP testing alone generally does not satisfy this requirement, rather testing of the compound  is usually needed with and without the drug product.
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Jennifer Hefele Wald
Manager, Global Regulatory Affairs
Lake Forest IL
United States
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Original Message:
Sent: 10-28-2013 08:30
From: Rachel Thornton
Subject: extractables/leachables discussion in BLA/sBLA

I should clarify that I'm not talking about the E/L for the primary packaging, but for all the product-contact materials used in the process.  I know in the past (> 5 yrs ago) such discussion was not included in our filings, but it is our (RA-CMC's) sense that at least a summary discussion of the issue is expected in the filing, esp. for biologics.  But some concrete examples would be helpful.

-------------------------------------------
Rachel Thornton
Associate Director
UCB
Smyrna GA
United States
-------------------------------------------






Original Message:
Sent: 10-25-2013 10:47
From: Rachel Thornton
Subject: extractables/leachables discussion in BLA/sBLA

A few years ago, at my previous company, we were noticing a trend of increasing concern from FDA re. extractables/leachables for a new application or a new manufacturing facility, and particularly an expectation that some discussion of extractables/leachables be present in the BLA or sBLA dossier.  Not a lot of detail, but at least a summary of what studies may have been done, risk assessments, etc.

Now, in my present company, we in RA are getting push-back, particularly from our European colleagues, on the necessity of including such information in the dossier.  They insist it is an inspection issue.  The concern is all around the timing of when the reports need to be approved - if it's going in the regulatory filing, it needs to be done a few months sooner.

I'm wondering if anyone has received feedback from FDA specifically requesting this information during regulatory review of the dossier, not only at inspection.

Thanks,
-------------------------------------------
Rachel Thornton
Associate Director
UCB
Smyrna GA
United States
-------------------------------------------