Industry groups and biopharma companies are seeking additional clarity from the US Food and Drug Administration (FDA) regarding draft guidance released in August on chemistry, manufacturing and controls (CMC) postapproval changes for biologics to be documented in annual reports.

The draft guidance notes that under FDA regulations, postapproval changes in the product, production process, quality controls, equipment, facilities or responsible personnel that have a minimal potential to have an adverse effect on product quality must be documented by biologic applicants in an annual report.

But drugmakers are seeking additional clarity, questioning whether this guidance will take precedence over previous guidance and wondering how it will align with a final ICH guideline on technical and regulatory considerations for product lifecycle management, known as Q12.

Industry group BIO, for instance, says it would be helpful for FDA to define when the potential for an adverse effect is determined.

“Is it the potential at the first thought of the change, after a risk assessment, after generating some data, after validation, or at time of implementation? This is important because as the change is analyzed and data are generated generally the potential for adversely affecting the product decreases,” BIO adds.

And in terms of alignment with Q12, “BIO notes that continuity and consistency of terms across various guidances and guidelines will be necessary to ensure clarity and consistency in expectations for both Sponsors and Regulatory Authorities.”

GlaxoSmithKline, meanwhile, says that the current draft does not include all instances of annual reportable changes as noted in previous guidance from 1997.

“With the interest to simplify and minimize confusion, it is recommended the Agency have a single guidance to refer to for categorization of post approval changes and incorporate the current guidance content into the original 1997 guidance,” GSK says.

Similarly, Pfizer says there “may be conflicts between this draft guidance document and other guidance documents,” noting that it’s difficult to determine which guidance takes precedence.

The Association for Accessible Medicines also seeks more specificity on changes to manufacturing sites and “particularly those which are a key part of the sterilization process for a biologic process, i.e., moving the vial thaw equipment to another building within the same manufacturing site.”

And Sanofi asks if this guidance will apply to biologic products approved under new drug applications that will be deemed to be licensed as of March 2020, which is part of the Biologics Price Competition and Innovation Act of 2009. AstraZeneca, Corning and others also offered specific comments on the draft.

Comments