DRUG REGISTRATION GUIDANCE DOCUMENT (DRGD) - BPFK

Drug Registration Guidance Document (DRGD)5.11. API Manufacturer is responsible to maintain and update the DMF. ThePRH should file a variation once they are notified with the changes to theDMF.5.12. API Manufacturer Obligations:Any change or addition, including a change in authorization related tospecific PRH, shall be submitted to the NPCB in duplicate andadequately cross-referenced to previous submission(s). The referenceshould include the date(s), volume(s), section(s), and/or pagenumber(s) affected.Should any change to a DMF is necessary, the API Manufacturer shallnotify each affected PRH who has referenced the DMF of the pertinentchange. Such notice should be provided well before making thechange in order to permit the PRH to supplement or amend anyaffected application(s) as needed.5.13. A DMF is not required for common inorganic salts (for example, sodiumchloride, and other common electrolytes) used and regarded as API inproducts such as injections and dialysis solutions, and simple organiccompounds available commercially in high purity (for example, naturaloccurring organic acids and their salts, including ascorbic acid and sodiumcitrate, and simple mono- and disaccharides such as glucose andsucrose). Although a DMF is not required for these active ingredients,evidence needs to be submitted by the finished PRH that the substance isobtained from a reliable source and consistently comply with theapplicable pharmacopoeial specifications. Any non-pharmacopoeialspecifications need to be assessed by the NPCB to determine theirappropriateness and adequacy to ensure the quality of the substance.5.14. Where a DMF is submitted for an API controlled according to apharmacopoeia monograph, the DMF should include a discussion of thepotential impurities most likely to arise during synthesis using the actualmanufacturing process described in the DMF together with evidence thatthese impurities are adequately controlled by the test proceduresdescribed in the pharmacopoeial monograph. Where particular impuritiesfound in the substance are not listed in the monograph, a justification(including toxicological data, if appropriate) should be provided. Details onthe principles for the control of impurities (e.g. reporting, identification andqualification) are outlined in the ICH Q3A, Q3B and Q3C guidelines.National Pharmaceutical Control Bureau (NPCB)First Edition, January 2013 Page | 320