FDA guidance outlines where to send “cross-center” master files
The US Food and Drug Administration (FDA) has issued a draft guidance to industry that specifies where sponsors should submit “cross-center” master files (MFs) that are referenced and intended to support more than one regulatory submission. The guidance applies to combination products and non-combination products.The guidance also provides hypothetical examples to illustrate the agency’s recommendations for determining the lead center. The guidance applies to MFs submitted to the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), the Center for Devices and Radiological Health (CDRH), and the Center for Veterinary Medicine (CVM).
MFs are voluntary submissions that provide confidential information about the facilities, processes, or materials used in the manufacturing, packaging, and storage of FDA-regulated products. MFs may also include other types of information, such as nonclinical evaluations, including toxicology data or Risk Evaluation and Mitigation Strategies (REMS).
Historically, some MF holders have submitted their documents to CDER, while others have submitted them to CDRH, when the MFs included information about the device component of a combination product led by CDER, according to the draft guidance.
“Although the MF can be referenced by a CDER-led combination product submission regardless of its hosting center, establishing a consistent process for designating which center should receive these MFs is expected to enhance efficiency for both MF holders and FDA reviewers,” the draft guidance states.
MFs hosted in CBER are referred to as MFs. They can be Type II, III, IV, or V Drug Master Files (DMFs) or Master Files for Devices (MAFs). Master files hosted in CDER are referred to as DMFs. They can be Type II, III, IV, or V. Master files hosted in CDRH are referred to as MAFs.
The guidance states that “although the general MF concept is similar across the four medical product centers, the recommendations for submitting MFs and the MFs hosted by (i.e., located in) each center have aspects unique to that center (e.g., how to submit, content, format, naming convention, storage system).”
An MF is deemed “cross-center” if it is accessible and reviewed by FDA personnel from multiple centers. When reviewing an MF, the lead center can request expertise from another center by submitting a consult request for a specific aspect of a product, such as its indication, formulation, design, or performance.
The following scenarios illustrate when staff from multiple FDA centers may need to review an MF to evaluate the referencing submission:
- A regulatory submission for a CDER-led drug-device combination product, such as a drug-filled autoinjector, references a CDER MF that contains information about the container closure system for the device constituent part. CDRH will need to access the MF.
- A regulatory submission for a CDRH-led drug-device combination product, such as a drug-eluting stent, references a CDER MF that contains information about the drug constituent part. CDER will need to access the MF to complete a consultation request from CDRH about the drug constituent part.
The guidance states that “when an MF contains information that will support a regulatory submission for a combination product, the recommended hosting center is generally determined based on the lead center and which constituent part is the subject of the MF. MFs that will be referenced by regulatory submissions for combination products should typically include information about only one constituent part of the combination product.”
There are instances in which an MF for a non-combination product may reference multiple centers. For example, an MF may contain information about an inactive ingredient that is intended for use in both a CBER-regulated biological product and a CDER-regulated drug. In these cases, the center that receives the first referencing submission is recommended to host the MF.
The guidance recommendations apply to new MF submissions only. The agency advises MF holders against resubmitting previously submitted MFs that do not adhere to these recommendations.
The public has 90 days to provide comments on the guidance, which has not yet been posted in the Federal Register.
Guidance
