FDA 483 - Delta Pharma, Inc. - May 24, 2016

This FDA Form 483 details numerous deficiencies at an outsourcing facility producing injectable drug products. Key issues include a lack of validation for sterilization processes, specifically for non-sterile (b)(4) used in production, and the sterilization (b)(4) for finished products, stoppers, vials, and tubing. Depyrogenation processes using an (b)(4) are also unvalidated, and industrial-grade (b)(4) is used for cleaning glassware.

Environmental monitoring is severely deficient, lacking validation and continuous monitoring for the incubator, proper environmental condition monitoring in aseptic areas, personnel monitoring for each production, and viable air monitoring during cleanroom certifications. Microbial limits are not established, and positive/negative controls are not performed for environmental testing.

Equipment calibration is not routinely performed or documented for critical items like the (b)(4), incubator thermometer, refrigerator thermometers, scales, and pH meter. Drug product release testing is inadequate, lacking appropriate laboratory determination of conformance. Preservative effectiveness is not tested through expiration dates, and time limits for production phases are not established. Hold time studies for sterilized glassware and containers/closures are absent.

Batch production records are incomplete, lacking individual sign-offs, start/stop times for time-limited steps, temperature ranges for heating steps, and calculated yield percentages with acceptable ranges. Personnel gowning is inappropriate, missing forehead or eye covers. Finally, there is no written stability testing program, and labels for outsourced drug products lack required information