Type 4 drug master files

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. 

Food and Drug Administration. Guidance for Industry, Submitting Type V Drug Master Files to the Center for Biologies Evaluation and Research, FDA, Rockville, MD, 2001. 

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 ... 

Type 1 Drug Master Files are no longer used. They were once used to describe facilities. In an effort to better define the relationship between the field investigators... 

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. 

IV. ROLE OF DRUG MASTER FILES (DMF)—TYPE II AND IMPURITIES EVALUATION... 

These arise from the synthesis, preparation, or degradation of compendial articles. In general, USP provides tests to limit these impurities. However, since process-related impurities are different for varying processes, holders of Type II Drug Master File(s) and NDA/ANDA sponsors should address the impurities that are unique to their processes. 

A Type II DMF may be filed for a drug substance (DS) or for a DS intermediate. For NDAs, drug substance information is usually filed in the NDA itself, instead of a DMF. The Agency reviews Drug Master Files only in connection with the evaluation of a filed IND, NDA, AND A, or supplemental application when a letter authorizing such review is provided. There is no regulatory requirement that a DMF be submitted to support any of the above applications. The agency does not approve or deny approval to a DMF. 

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. 

Excipient and vendor selections can greatly influence the new drag development timeline, product performance, and acceptance of final products. Compendial excipients have composition consistent with monographs published in compendia such as USP-NF these are the better-characterized excipients. These excipients most likely possess desirable qualities and are preferred excipients for pharmaceutical formulations. Non-compendial excipients can also be used for drug products if they are supported by Type IV dmg master files (DMFs) in regulatory dossiers. Overall, a good excipient supplier should 29... 

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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