Authorisation of Generic Drugs in the USA: Requirements on APIs Stability Data for US Drug Master Files

Authorisation of Generic Drugs in the USA: Requirements on APIs Stability Data for US Drug Master Files
According to the new Generic Drug User Fee Act (GDUFA) for the marketing authorisation of generic drugs in the USA, the Drug Master File (Type II) for APIs must undergo a completeness assessment (see our GMP News from 11 October 2012). The approach is described in the Draft Guidance for Industry entitled “Initial Completeness Assessment for Type II API DMFs under GDUFA” from October 2012.

Which information about the stability of the API contained in a generic drug is required in a Drug Master File submitted for a marketing authorisation application? The answers to this question can be found in a Q&A document published by the FDA on 26 August 2013 entitled “Guidance for Industry; ANDAs: Stability Testing of Drug Substances and Products; Questions and Answers“. This Q&A document refers to the “Guidance for Industry; ANDAs: Stability Testing of Drug Substances and Products” which was released 2 months before and tackles a range of outstanding issues with regard to stability data of APIs and finished products for the marketing authorisation application of generic products.

The statements laid down in the Q&A document regarding the stability data of the API required in a DMF are explicit: in addition to the stability protocol and commitments, data demonstrating the beginning of stability studies have to be provided. The initial and one additional time point for the accelerated studies and long-term studies are sufficient. Yet, the DMF holder should provide amending data to keep the DMF as up-to-date as possible. This is the only way to ensure the successful completeness assessment by the reviewer in the Office of Generic Drugs (OGD) of the FDA. Furthermore, stability data from production scale batches are also accepted. Three production batches are necessary. The data must come from 6 months of accelerated data and long-term data covering the proposed retest period.

The Q&A document contains a range of other interesting clarifications like for example a concrete explanation of the term “small scale” with regard to the various dosage forms.



DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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