The Drugs Controller General of India (DCGI) has constituted a sub-committee to frame guidelines on post approval changes to pharmaceutical products in line with the global regulatory framework and followed in regulated markets.
The matter was deliberated during the Drug Consultative Committee (DCC) meeting held in Delhi in September this year to bring in similar guidelines for Indian pharmaceutical industry as per global regulations.
“The draft guidelines once framed will go to Drug Technical Advisory Board (DTAB) of the Union health ministry and finally to the stakeholders for review and recommendation,” informed Dr H G Koshia, Commissioner, Gujarat Food and Drug Control Administration (FDCA).
Based on the DCC recommendations, DCGI directed to form the sub-committee under the chairmanship of Dr B Venkateswarlu, joint director, Drugs Control Administration (DCA), Telangana with members being D K Tiwari, assistant commissioner (Drug), Uttar Pradesh Food Safety and Drug Administration Department (FSDA UP), Arvind Kukrety Deputy Drug Controller, Central Drugs Standard Control Organisation (CDSCO), West Zone, Ahmedabad, Dr H G Koshia, commissioner, Gujarat Food and Drug Control Administration (FDCA).
As per the US FDA guidelines, manufacturers of active pharmaceutical ingredients (APIs) who want to make changes to the drug substance (DS) manufacturing process during an application’s post-approval period should consult US FDA (Food and Drug Administration) new draft guidance released on September 10, 2018.
The 38-page draft (including 2 Appendices) entitled “Post-approval Changes to Drug Substances” has been completed as part of the commitment to the reauthorization of the Generic Drug User Fee Amendments (GDUFA II).
The document provides recommendations to holders of approved new drug applications (NDAs), generics (abbreviated new drug applications, ANDAs), new animal drug applications (NADAs), abbreviated new animal drug applications (ANADAs), and holders of drug master files (DMFs) and veterinary master files (VMFs) who may want to make a change to the drug substance manufacturing process during the drug product application´s postapproval period. However, the draft notes that it does not address postapproval changes to “peptides, oligonucleotides, radiopharmaceuticals; or drug substances isolated from natural sources or produced by procedures involving biotechnology; or nonsynthetic steps (such as fermentation) for semisynthetic drug substances.”
The draft guidance covers the following changes like facility, scale and equipment changes associated with all steps of drug substance manufacturing, specification changes to starting materials, raw materials, intermediates and the unfinished and final drug substance, synthetic manufacturing process changes, changes in the source of drug substance and changes to the container closure system of the drug substance.
The document notes that late-stage changes in the drug substance manufacturing process are generally viewed as “more likely to have an adverse impact on the quality of the drug substance and, consequently, on the drug product”. The discussion of the change being reported should be accompanied by a Risk Assessment (RA) for FDA review and recommended documentation.
The Drug Product (DP) documentation should be submitted as an annual report or supplement to the approved application depending on the risk associated with the change.
Change control is generally understood to be the responsibility of the Quality Control (QC) unit. Effective change control activities are key components of the Pharmaceutical Quality System (PQS).
Although the draft guidance does not repeat the concepts and principles explained in the GMP (Good Manufacturing Practice) and ICH guidance, FDA encourages the use of modern pharmaceutical development concepts, Quality Risk Management (QRM), and an effective PQS at all stages of the manufacturing process life cycle.