How is the management of DMFs done by API and drug product manufacturers

When the API manufacturer sells its API to a certain client, he also needs to present the quality documentation for that API, the DMF. To know more about DMFs, watch • What is a DMF (drug ma...
The DMF is also a regulatory document, so it must be shared with the regulatory agency so that it approves the API for it to be produced and commercialized. This communication with the regulatory agency in many cases is done through the DP manufacturer, however in the case of APIs with CEP, CADIFA, and DMFs approved by some other agencies, the API manufacturer himself will be in contact with the agency that approved the DMF.
So everytime the pharmaceutical industry wants approval for a new DP, the agency needs to receive not only the drug product regulatory submission, but also the DMF, so that the API can be approved for use in that DP, and GMP need to be shown. Once the agency approves the submission, this is the condition which must be commercialized - as per the documentation which was submitted and approved.
But we know that the lifecycle of drug products and APIs involves multiple changes. Something that may happen, for example, is that the API manufacturer develops a more efficient way of producing a certain API, and proposes a change to optimize the route of synthesis. Any change that the manufacturer proposes will lead to new documentation and should lead to a new version of the DMF, corresponding to that new condition; and the API manufacturer also needs to notify his clients, the drug product manufacturers, before implementing any change. This is because this change may impact the drug product, and in many cases, in can only be implemented once the regulatory agency evaluates the new documentation and data, and gives the approval.
So what are the responsibilities of the API and drug product manufacturers in the management of DMFs?
This depends on the moment where we are in the product lifecycle.
For APIs which are still in development, the API manufacturer needs to create the DMF, which will be shared with clients and regulatory agencies only once it's ready.
in the case of already commercialized APIs which are actively produced, the DMF is ready, and we may face two different situations. The first, where the API is regularly supplied to clients which already have their drug product submission approved by regulatory agencies.
Or, in the second case, there is a potential new client, who bought some amount of this API to develop a new drug product, but will only become a commercially active client once the regulatory agency approves that drug. These clients will receive the DMF referring to the API that they have bought, and the responsibility of the API manufacturer is to ensure that this DMF is updated according to the condition which is in currently in place - hence he needs to inform his clients of any change he proposes, as well as the regulatory agency directly when applicable.
The drug product manufacturer, on the other hand, also needs to make sure that the condition which is in place at the API manufacturer side corresponds to the updated DMF that he has and to the condition which was approved by the regulatory agency, when the drug was already approved.
For this reason, a very close relationship and an open communication between the drug product and API manufacturers must be in place - because any change in relation to the previous DMF version may potentially impact the drug product manufacturer - both in the case of a drug which was already approved, and when it's still in development. If the drug product or API are still in development, there won't be a regulatory impact, but if the drug product was already approved, it's also important to assess if any variation procedure needs to be done, and which kind.
In the case of drug products under development, the dossier is still in progress, and the DMF will be part of this documentation which will be submitted to the regulatory agency in the future. In this case, the drug product manufacturer needs to evaluate the DMF and work very closely with the API manufacturer, to ensure that the DMF meets the regulatory requirements for the dossier to be approved - which would make him a new active client for that API supplier.
Managing DMFs is not a sole responsibility of the API manufacturer or the drug product manufacturer. Instead, it should be shared between both. The lifecycle of DMFs requires robust risk assessments for any change that is proposed, and the communication needs to be very open and clear between API manufacturer, drug product manufacturer, and the regulatory agency.
After all, it's in everyone's interest that the API has the appropriate quality so that the drug product also reaches the patient with the desired quality, and that the commercialization continues in an efficient way so that drugs are available on the market, allowing patients to receive the treatments that they need.
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[@rashvankhan5319]

Nice explanation madam

[@bhushanborse917]

Fernanda you are providing valuable information, the way you make video, it gives clear idea about the concept

[@FernandaWaechter]

thank you dear!