What is a DMF (drug master file)?

Versão em português: • O que é um DMF (drug m...
Any drug product is actually a combination of excipients with one or more APIs (active pharmaceutical ingredients), that is, the component responsible for the therapeutic effect.
DMF means Drug Master File, and corresponds to the main document which describes the quality of a specific API.
Depending on where we are, it may also be called ASMF (active substance master file), APIMF (active pharmaceutical ingredient master file), or DIFA (Dossier of the API) in the case of Brazil.
The DMF is a document which is essential for the development of a new drug by the pharmaceutical industry, because it basically tells us the story of that API. But what exactly do we expect to find in a DMF?
When we open the DMF, we will first find out which API it refers to - its name, chemical structure, CAS number, and some properties - this is the general information section.
We will then find out where it is produced, who is the manufacturer and the manufacturing site address.
And after that we will be faced with the route of synthesis used by this manufacturer to produce this API - is it a chemical synthesis? Is it through fermentation? What are the steps and which materials are used?
This manufacturing process was developed and validated by the manufacturer, and the results of the 3 validation batches will be used to develop the DMF.
Next, the manufacturer will provide proof that when that route of synthesis is used, this is indeed the API that is obtained, so we will usually see infrared, NMR and mass spectra, proving the structure of the API. Here we will also see information about isomerism and the polymorphic form - this is the characterization section.
But this route of synthesis may generate impurities. Each of the compounds from the route may be a potential impurity, in case it is not eliminated. Besides, other impurities may form through degradation of the API, and all this should be described in the DMF, in the impurity section which comes next. The manufacturer needs to explain how each of these impurities is controlled. Is there an in process control in place? Was the elimination demonstrated through the purge factor calculation? Or is it controlled in the API specification?
And this is the section that comes next - the specification - that is, all the tests which are performed in routine during the quality control of the API - to ensure that only batches with the desired quality will be considered approved.
Here we will also find out if this API meets any pharmacopoeial monograph - that is, does it comply with certain quality standards.
But for the manufacturer to find out if the API complies with the specification, it needs to have analytical procedures in place, and these need to be described in the DMF as well.
Also, these methods need to be validated to show they are adequate, and we also need to see some results of batches tested with these methods, demonstrating that in fact the API complies with this specification.
Finally, we will also see a justification for the specification: why were these tests chosen for the quality control of the API?
After this, there is a section for reference standards - here the manufacturer will have to present all the certificates and when applicable the characterization of any standard which was used in the analytical validation - after all, we need to be sure of their identity.
Now, once the API is produced, it needs to be packed before it is commercialized. The container closure system section will describe which packing material is used, and then - in the stability section - we will find out for how long this API can be stored when packed in this material, and in which conditions.
The DMF not only demonstrates the quality of APIs which are already actively produced and marketed, but it will also be used in regulatory submissions when approval is requested for any other new drug for which that API is not yet approved. Hence, it needs to comply with ICH guidelines which describe the technical requirements that need to be met, and it also needs to meet other regulatory requirements which may be relevant for the country where it will be marketed.
One of the ICH guidelines which is usually applied to DMFs is the M4Q, which describes the organization of the documentation and recommends a format called CTD - common technical document.
The CTD format is applicable not only to the API, but to the complete drug product regulatory submission, and includes a series of sections so that the information can be more easily found.
The DMF consists of 7 of these sections, which will be explained in more details in the videos that will follow - one by one.
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[@septiaanrml]

Such a great vid, very well explained! And this is coming from someone who just recently entered regulatory affairs :)

[@FernandaWaechter]

Thank you, that's great to know! :)

[@Sunriserrs]

Nice content

[@AshwaniKumar-xi5xq]

Very informative as always

[@zahraddeennuhu8186]

Wow ,very well explained.

[@FernandaWaechter]

Thank you dear!

[@rashvankhan5319]

Nice explanation

[@bhushanborse917]

Good information Fernanda. I am waiting for Nitrosamine series.

[@anapatisuneela5097]

Basic information on DMF was briefly explored.

[@tusharganage9814]

Keep Going dear this help me Lot ❤😊

[@FernandaWaechter]

I'm glad to know this was helpful! :)

[@ganeshkilli8265]

❤

[@zahraddeennuhu8186]

Please what about types and Submission of DMF ?

[@FernandaWaechter]

In this video we have only talked about type II DMF - for the drug substance. Other types of DMF can be found here www.fda.gov/drugs/drug-master-files-dmfs/types-drug-master-files-dmfs