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Regulatory Focus™ > News Articles > FDA Offers Final Guidance on CGMP Requirements for Combo Products

FDA Offers Final Guidance on CGMP Requirements for Combo Products

Posted 10 January 2017 | By Zachary Brennan 

FDA Offers Final Guidance on CGMP Requirements for Combo Products

The US Food and Drug Administration (FDA) on Tuesday released final guidance describing and explaining the current good manufacturing practice (CGMP) requirements for combination products, first released in January 2013.

The guidance addresses general considerations for CGMP requirements for these drug-drug, drug-device, drug-biologic or biologic-device combination products and the purpose and content of specific provisions from 21 CFR part 4.

The guidance also discusses the role of the lead center and other agency components related to combo product CGMP issues, as well as hypothetical scenarios intended to clarify how to comply with certain requirements addressed by presenting compliance considerations for specific types of combo products.

The guidance follows FDA’s finalization last month of a rule on combo product postmarket safety. The recently passed 21st Century Cures law also includes several provisions linked to the regulation of combo products, specifically requiring FDA meet with sponsors to agree early in development on how best to meet the agency’s standards for approval, as well as more clarification on how dispute resolutions work when different FDA centers disagree on a combo product.

The additional clarity comes as companies and industry groups have expressed concerns with the consistency and clarity of FDA’s communications related to combination product review, according to an independent assessment of the combo product intercenter consult process.

Final Guidance Details

The finalization of the draft guidance from 2015 follows the release of comments on the draft from several major pharmaceutical and medical device companies, some of which sought more clarification.

For instance, Pfizer sought clarity on seven parts of the draft, including sections on design controls for early-phase investigational combo products, CGMP information in marketing applications and cross labeled combo products.

AbbVie also sought clarification on the cross-labeled requirements for combo products, despite their being outside the scope of 21 CFR Part 4.

“We recommend the CGMP requirements for cross-labeled combination products be incorporated into the relevant sections of the guidance, and all footnotes related to cross-labeled combination products be removed to ensure this key information is not inadvertently neglected,” Lauren Hetrick, AbbVie’s senior director for regulatory policy and intelligence, wrote.

FDA, meanwhile, in response to the comments on Tuesday said it carefully considered the comments and, “where possible, has incorporated into the final guidance additional detailed discussion of how the requirements apply and acceptable CGMP compliance approaches. FDA encourages combination product manufacturers to contact the lead Center for their combination product and/or the Office of Combination Products if they have questions on CGMP compliance or approaches they are considering for meeting CGMP requirements.”

The 59-page final guidance analyzes hypothetical scenarios that illustrate how to comply with certain CGMP requirements for a prefilled syringe, drug-eluting stent and drug-coated mesh.

Current Good Manufacturing Practice Requirements for Combination Products; Guidance 


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