Drug Master File process

Description of the bulk drug substance, including structural and molecular formula, process impurities or degradants, specifications, rationale for specifications, safety, approved supplier(s), test methods, validation, and stability. Include basic information on synthesis or derivation of the drug substance, or if applicable, reference supplier drug master file. 

Drug Master Files (DMF). DMF is a submission to the FDA that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. 

Drug Master File (DMF) completed, including information on facilities, processes, and articles used in manufacturing, processing, packaging, and... 

Drug Master File Drug Master Files (DMF) contain information on the processes and facilities used in drug or drug component manufacture and storage and are submitted to the FDA for examination and approval. 

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 ... 

Both processes typically require extensive validation by the component manufacturer, a description of the process in a Drug Master File (DMF), quality audits by customers, and perhaps FDA approval before RtS or RtU components are utilized. Nevertheless, RtS and RtU are trends that are moving rapidly most major rubber component manufacturers now market RtS components.f A list of pharmaceutical rubber manufacturers is shown in Table 7. 

Sources of raw materials, especially those critical to a new product s functionality, should be identified. Availability and costs should be ascertained to aid in the planning process. Care should be taken to ensure that new drug actives and, when possible, excipients are secured from vendors with a current acceptable FDA compliance profile and a drug master file. 

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. 

Profile This privately held company was founded in 1972. It is a full-service drug synthesis and chemical services company that performs a variety of laboratory, process scale-up, and manufacturing tasks including development of processes and synthesis routes for new medicinal products, validating bulk pharmaceutical processes, and authoring Drug Master Files. The company also has a pilot plant/small volume manufacturing site in North Andover, Massachusetts. 

Part II relates to the quality of the product and gives details of its chemical, pharmaceutical and biological testing. Data should be provided in respect of qualitative and quantitative particulars of the constituents, description of the method of preparation, control of starting materials, control tests on intermediate products, control tests on the finished product and stability tests. In cases where the active ingredient is made by a manufacturer other than the applicant or the product manufacturer, some of the information required in Part II may be presented in a separate file, the Drug Master File, to maintain the confidential nature of the synthetic process. 

If the herbal medicinal product does not contain the herbal drug itself but a preparation, the comprehensive specification on the herbal drug must be followed by a description and validation of the manufacturing process for the herbal drug preparation. The information may be supplied either as part of the marketing authorization application or with the help of the European Drug Master File procedure. 

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. 

A recent FDA guidance for industry (FDA 2006) provides the Agency s current thinking on how to evaluate out-of-specification (CX)S) test results. Forpurposes of this document, the term CX)S results includes aU test results that faU outside the specifications or acceptance criteria established in drug applications, drug master files (DMFs), official compendia or by the manufacturer. The term also applies to aU in-process laboratory tests that are outside of established specifications. This document is intended for GMP studies, but it can be generalized for aU applications. The foUowing discussion represents an attempt to do so, as an adaptation of seven key recommendations (FDA 2006). 

---