FDA Sent These 6 Warning Letters for Pharma Companies | May 2017

We took a snapshot of the 6 warning letters the FDA sent to pharmaceutical companies last month.  Drug manufacturing violations ranged from failing to establish adequate written procedures to not submitting periodic adverse drug experience reports.

From pharmaceuticals in New Jersey, China, and more, here they are (starting with the most recent):

  • Yusef Manufacturing Laboratories, Clearfield, UT- 5 violations:
    • The firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
    • The firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow such written procedures (21 CFR 211.22(d)).
    •  The firm does not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient and freedom from objectionable microorganisms, prior to release (21 CFR 211.165(a), (b)).
    • The firm failed to test samples of each component for conformity with all appropriate written specifications for identity, purity, strength, and quality (21 CFR 211.84(d)(1), (2)).
    • The firm failed to establish and to follow adequate written procedures for production and process control designed to assure that the drug products manufactured have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
  • Med-Pharmex, Inc., Pomona, CA– 6 violations:
    • The firm does not follow procedures designed to prevent microbiological contamination of drug products purporting to be sterile [21 C.F.R. 211.113(b)]. For example, on January 17, 2017, during the aseptic filling of (b)(4).
    • The firm does not exercise appropriate controls over computer related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel [21 C.F.R. 211.68(b)].
    • The firm’s aseptic processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure [21 C.F.R. 211.42(c)(10)(iii)]. Specifically, site Standard Operating Procedure ENP-0002-07-07, Certification of Classified Cleanrooms, Effective 10/20/15, indicates airflow velocities of HEPA filters are recertified by an outside vendor at a minimum of (b)(4) regular intervals. Regarding recertification activities conducted in April 2016 and October 2016.
    • The firm’s aseptic processing areas are deficient regarding the system for monitoring environmental conditions [21 C.F.R. 211.42(c)(10)(iv)].  Specifically, sites firm’s SOP-0024-05-17, Environmental Monitoring Program, Effective March 7, 2016, indicates a “(b)(4)” and set a (b)(4) contamination recovery rate limit for the following categories in the ISO 5 East Fill Room (Room (b)(4)): active air samples, settling plates, contact plates/swabs, and gloves/garments.
    • The firm does not have an adequate system for cleaning and disinfection of the aseptic processing area [21 C.F.R. 211.42(c)(10)(v)].  Specifically, on January 17, 2017, during the aseptic filling of (b)(4), our investigators observed the following conditions in East Fill Room (Room (b)(4)).
    • The firm does not have laboratory records that include complete data derived from all tests necessary to assure compliance with established specifications and standards, including examinations and assays.  [21 C.F.R. 211.194(a)].  Specifically, on January 26, 2017, our investigator observed sites microbiologist read (b)(4), (b)(4) for Tri-Otic Ointment, lots H6510 and H6514, using the antibiotic zone reader (instrument Asset (b)(4)).  Our investigator verified sites microbiologist recording the correct value as read from the plate reader; with a range of (b)(4) to (b)(4).  Then our investigator copied the handwritten zone diameter test results taken at the time of testing for the (b)(4) and (b)(4) zones of the standard series from the microbiologist’s issued worksheet.  
  • B. Braun Medical, Inc., Irvine, CA– 2 violations:
    • Failure to establish and follow adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(d)).
    • Failure to routinely calibrate, inspect, or check according to a written program designed to assure proper performance of automatic, mechanical, electronic equipment, or other types of equipment, including computers, used in the manufacture, processing, packing, and holding of a drug product (21 CFR 211.68(a)).

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  • Changzhou Jintan Qianyao Pharmaceutical Raw Material Factory, Changzhou City, China – 4 violations:
    • Failure to implement a system for managing quality encompassing the organizational structure, procedures, processes, and resources, as well as activities to ensure confidence that the API will meet its intended specifications for quality and purity. Failure to define and document all quality-related activities.
    • Failure to have adequate written procedures for the receipt, identification, quarantine, storage, sampling, testing, handling, and approval or rejection of raw materials.
    • Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
    • Failure to prepare adequate batch production records and record the activities at the time they are performed.
  • Vertical Pharmaceuticals, Inc., Bridgewater, NJ- 2 violations:
    • Failure to develop written procedures for the surveillance, receipt, evaluation, and reporting of postmarketing adverse drug experiences (ADEs) as required by 21 CFR 314.80(b).
    • Failure to submit periodic adverse drug experience reports annually for an application which was approved three or more years ago as required by 21 CFR314.80(c)(2).
  • Phillips Co., Millerton, Ok- 6 violations:
    •  The firm does not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient and absence of objectionable microorganisms, prior to release (21 CFR 211.165(a) and (b)).
    •  The firm failed to use equipment constructed to ensure surfaces that contact components, in-process materials, or drug products are not reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirement (21 CFR 211.65(a)).
    • The firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(d)).
    • The firm failed to test samples of each component for conformity with all appropriate written specifications for identity, purity, strength, and quality (21 CFR 211.84(d)(2)).
    • The firm failed to establish written procedures for production and process control designed to assure that the drug products manufactured have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
    • The firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).

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