INVESTIGATIONAL DRUG RESERVE SAMPLES AND RECORDS

INVESTIGATIONAL DRUG RESERVE SAMPLES AND RECORDS from IND production batches should be retained for at least two years after the related NDA is approved, according to a draft guideline recently released by FDA on current good manufacturing practice (CGMP) considerations in the preparation of IND products. Production and control records related to batches of IND products and reserve samples from those batches, FDA states, should be retained "for at least two years after termination or discontinuance of the relevant IND, or at least two years after approval of the relevant new drug application." In addition to retention of samples and records in IND drug production, the guideline explains CGMP requirements regarding component and process controls, equipment and product identification, and calculation of yield. FDA recognizes in the guideline that factors in the preparation of investigational drugs may result in significant discrepancies between theoretical and actual yields, and that those discrepancies may not necessarily imply problems. However, the guideline states, "where yield discrepancies are significant, it is essential that products not be released unless and until there is reconciliation of all materials used at each appropriate phase of production and other appropriate investigations have been conducted." The new guideline is not intended to be a complete review of CGMPs for investigational drug production, FDA explains, but to address those areas for which agency guidance and clarification is most freqently requested. In the Feb. 26 Federal Register notice of availability, FDA notes that the draft guideline may be amended to address other aspects of IND manufacturing operations in response to comments received. Comments on the guideline should be submitted by May 26. The guideline is available from FDA at: Dockets Management Branch, Rm. 4-62, 5600 Fishers Lane, Rockville, MD 20857. The guidelines point out that compliance with the CGMPs is required at the point when a new drug is being prepared for use in clinical trials. At this stage, FDA explains, "the drug product must be produced in a qualified facility, using laboratory and other equipment that has been qualified, and processes must be validated. There must be written procedures for sanitation, calibration and maintenance of equipment, and specific instructions for the use of the equipment and procedures used to manufacture the drug product." Ensuring that the CGMPs are followed during clinical production is crucial, FDA notes, as "product contamination and wide variations in potency can produce substantial levels of side effects and toxicity and even produce wide sweeping effects on the physiological activity of the drug." While the CGMP regulations are not applicable to the preparation of drugs during preclinical toxicological and chemistry studies, the guideline notes, "it is nonetheless important to process materials under conditions [that will] assure their integrity, and to maintain adequate records." FDA concern over CGMPs for clinical supplies has been heightened by the potential for wider clinical drug distribution under the new Treatment IND regulations. According to the agency's compliance office, the production facilities of Treatment IND applicants will be fully inspected for CGMP compliance as part of the review process.