Drug Master File Requirements and Submission in the United States
The technical review of a Type II drug master file (DMF) is conducted by the US Food and Drug Administration (FDA) when an authorized party submits an application (drug product dossier or another DMF), along with the list of abbreviations of the DMF to be referenced, to the US FDA. The technical review is conducted with respect to the use of the DMF material described in the application. The FDA reaches out to the DMF holder if any specific concerns need to be addressed during the review before approving the said application.
Active Substance Master File Framework in the EU and UK
The active substance master file (ASMF) consists of the applicant’s part (AP) and the restricted part (RP). The AP provides information to the marketing authorization holder (MAH) for evaluating the drug substance, whereas the RP contains confidential details about manufacturing methods, intermediates, and quality controls that are not shared with the MAH. An ASMF is submitted to regulatory authorities in the electric common technical document (eCTD) format, which includes summaries and a letter of access that allows the regulators to assess the ASMF, along with a related marketing authorization application (MAA). The authorities conduct a technical review of the ASMF when an authorized party submits an MAA along with the corresponding letter of access. The ASMF holder is obligated to maintain the ASMF and must timely communicate any updates to the MAH and regulatory authorities.
A certificate of suitability (CEP) is issued by the European Directorate for the Quality of Medicines & HealthCare (EDQM) to certify that a drug substance meets the European Pharmacopoeia standards. The manufacturer, as the CEP holder, manages the application and the life cycle of the certificate. To obtain a CEP, applicants must submit a request to the EDQM’s Certification of Substances Department (DCEP). Updates to the CEP are communicated through immediate or annual notifications, with the annual notification date set at 12 months post the implementation of the change, and not from the CEP issuance date onward.