Drug Master File regulations

Information on existing or new excipients can be described and provided to the FDA in an NDA directly. Alternatively, the manufacturers of excipients may prepare and submit type IV Drug Master Files (DMF) to support the use of an excipient in one or more NDAs. The DMFs are discussed in FDA s regulations under 21 CFR Section 314.420 and the FDA-issued Guidance for Drug Master Files (8). When authorized by the DMF submitter (i.e., the excipient manufacturer) and cross-referenced by an NDA submitter, the FDA reviews the DMF to make determinations on the safety, manufacture, and quality of the excipient use in the new drug that is the subject of the then pending NDA. The DMF becomes active when reviewed in conjunction with the review and approval of an NDA. 

The DMF should include the name, address, phone number of holder, a description of items that are the subject of the DMF, a list of materials of construction, and the sources of materials of construction. The standards for testing incoming, in process, and release are sometimes different. There are five types of CDER Drug Master Files listed in the Code of Federal Regulations Title 21 S314 Drug Master Files (DMF). They are as follows ... 

Code of Federal Regulations Title 21 314. 420, Drug Master Files, Parts 300 to 499, Office of Federal Register, National Archives and Records Administration (current version). Government Printing Office Washington, DC, 2001. 

In the UK, some of the more complex Type 11 changes, such as the addition of new indications and the addition of new sources of active ingredients which require the assessment of a new drug master file, have been specified in the fees regulations as attracting a complex fee and consequently are identified as Type II complex. 

Sooner rather than later, CTD-formatted dossiers should also be made acceptable for other types of products (for example generics, line extensions, herbals, radiopharmaceuticals and blood products). Also, applications for clinical trials (for example CTX in the UK, IND in the USA), as well as applications for variations, and Drug Master Files could be formatted according to the CTD guideline. However, before this becomes reality, national regulations and guidelines need to be adapted accordingly. 

The primary focus of this chapter will be on conventional, low-molecular-weight APIs manufactured by chemical synthesis. It is recognized that APIs also are derived from fermentation, proteins, peptides, etc. Specific regulations and guidelines exist for these compounds, which will not be covered in this work. This chapter will also focus mainly on the regulations as they apply to innovator companies seeking approval for new chemical entities. Separate but similar requirements exist for the development and maintenance of drug master files (DMFs) submitted by bulk chemical... 

If the entire API and/or key process intermediates are manufactured at contract facilities, the information required in this section differs from country to country. In the United States, the contract manufacturer for an API or intermediate is generally identified in the filing, along with specific reference to their U.S. drug master file. A letter from the contract manufacturer, allowing FDA review of the DMF as part of the sponsor marketing application, is also needed. In the EU at this time, the regulations allow DMF reference only for the finished API. 

Although LYOGUARD trays are not subject to FDA regulation, a Type II material master file has been submitted to the FDA to be referenced as needed for new drug manufacturing submissions. Upon request, W. L. Gore Associates, Inc. may provide written permission to reference the material master file with the FDA. 

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