Center for Biologics Evaluation and Research to regulate biological master files

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The US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) is now responsible for administering master files for biological drugs, which could create some challenges for biological manufacturers.

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Manufacturers submit a Drug Master File (DMF) to FDA to inform them of the manufacturing process used for a drug, which helps the agency to review the suitability of a drug for clinical trials or commercialization. 

DMFs are also an important way for manufacturers to protect proprietary information, as their contents are confidential. This means that the contents of a DMF can be cross-referenced by a partner but not accessed.

Previously, DMFs for biological drugs had been administered by FDA’s Center for Drug Evaluation and Research (CDER). However, as of 23 March 2020, master files for biological drugs will now be regulated by CBER. 

This change is related to the 2009 Biologics Price Competition and Innovation Act (BCPI Act), which promotes the development of more affordable, biosimilar versions of biological drugs. 

However, the change could also generate some challenges for biological manufacturers, as outlined below:

• Biological manufacturers may no longer cross-reference another company’s DMF for drug substance, drug substance intermediate, or drug product.
FDA now expects a biological manufacturer to understand and control the entire manufacturing process. This limits the opportunities for partnering (but increases the potential profits for an individual company).

• Manufacturers should get in touch with FDA to confirm a DMF is appropriate for the product’s intended use.
Several biologicals previously approved as new drug applications (NDAs) were recently re-classified as biologicals license application (BLAs) [1] and FDA has identified 89 products where oversight responsibility is being transferred from CDER to CBER. This means communication with FDA will be particularly important for new product and DMF submissions. For example, proprietary cell culture media can still be submitted through a Type II master file but cross-referencing an entire manufacturing process would not be appropriate. 

• DMF numbers for biologicals are no longer issued through CDER’s NextGen portal.
Sponsors must now submit an email request through CBER’s Regulatory Information Management Staff. The email must include the sponsor’s name and address, primary point of contact information, anticipated submission date, biological product name and indication, and relevant CBER review office. 

The regulatory transition from CDER to CBER will affect all previous and upcoming biological DMFs and marketing approvals, however, it is not yet known whether CBER will honour past reviews and approvals made by CDER.

It is possible that sponsors may have to re-defend their submissions and regulatory strategies, which could delay approval times. Sponsors can provide FDA with feedback on any impact on master file submissions and BLA approvals.

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1. GaBI Online - Generics and Biosimilars Initiative. FDA to transition NDAs to BLAs []. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Sep 4]. Available from: 

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Source: Bioprocess Online, US FDA

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