Warning Letters

FDA Sent These 13 Warning Letters for Pharma Companies | August 2016

We took a snapshot of the 13 warning letters the FDA sent to pharmaceutical companies last month.  Drug manufacturing violations ranged from failing to “maintain written records” to failing to wear “clothing appropriate to protect drug product.”

From pharmaceuticals in Brazil, India, China, and 6 US states, here they are (starting with the most recent):

  • Lima & Pergher Industria e Comercio S/A, Minas Gerais, Brazil – 4 violations:
    • Failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(d)).
    • Failed to establish and follow appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile (21 CFR 211.113(a)).  
    • Approved and released for use one or more lots of components, drug product containers, or closures that did not meet the appropriate written specifications of identity, strength, quality, and purity and related tests under 21 CFR 211.84(d) (21 CFR 211.84(e)).
    • Failed to ensure that its drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
  • Pan Drugs Limited, Vadodara, India – 4 violations:
    • Failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products (21 CFR 211.22(a)).
    • Failed to maintain the buildings used in the manufacture, processing, packing, or holding of a drug product in a clean and sanitary condition and to keep them free of infestation by rodents, birds, insects, and other vermin (21 CFR 211.56(a)).
    • Failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).
    • Failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
  • Xinxiang Tuoxin Biochemical Co., Ltd., Xinxiang City, China – 2 violations:
    • Failed to properly maintain equipment used in the manufacture of API and minimize the risk of contamination where open equipment is used.
    • Failed to properly maintain, repair, and keep clean buildings used in the manufacture of API in a manner that prevents contamination where open equipment is used.
  • College Pharmacy, Colorado Springs, CO – 5 violations:
    • Failed to validate the procedures used in aseptic and sterilization operations. (21 CFR 211.113(b))
    • Failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas. (21 CFR 211.42(c)(10)(iv)
    • Failed to establish an adequate system for cleaning and disinfecting the room and equipment to product aseptic conditions. (21 CFR 211.42(c)(10)(v))
    • Failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination. (21 CFR 211.28(a))
    • Failed to withhold components from use until the lot has been sampled, tested, examined and released by the quality control unit. (21 CFR 211.84(a))
  • Frontida BioPharm, Inc., Exton, PA – 1 violation:
    • Failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products; and the authority to review production records to assure that no errors have occurred or, if errors have occurred, assure that they have been fully investigated. (21 CFR 211.22(a))
  • Unimark Remedies Ltd., Mumbai, India – 6 violations:
    • Vapi Facility (FEI: 3004414652)
      • Failed to adequately investigate and document out-of-specification results and implement appropriate corrective actions.
      • Failed to evaluate the potential effect that changes in the manufacturing process may have on the quality of API.
    • Bavla Facility (FEI: 3008117347)
      • Failed to adequately investigate and document out-of-specification results and implement appropriate corrective actions.
      • Failed to ensure that test procedures are scientifically sound and appropriate to ensure that API conform to established standards of quality and/or purity.
      • Failed to maintain training records of employees involved in the manufacture of intermediates or API.
      • Failed to properly keep buildings and facilities used in the manufacture of API in a clean condition.
  • Zhejiang Hisoar Pharmaceutical Co., Ltd., Taizhou City, China – 3 violations:
    • Failed to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
    • Failed to prevent unauthorized access or changes to data, and to provide adequate controls to prevent manipulation and omission of data.
    • Failed to record activities at the time they are performed.
  • Huzhou Aupower Sanitary Commodity Co., Ltd., Huzhou City, China – 5 violations:
    • 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, prior to release (21 CFR 211.165(a)).
    • Failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
    • Failed to establish 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)).
    • Failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).
    • 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).
  • Sentara Enterprises Inc., (dba Sentara Home Infusion Pharmacy Services), Chesapeake, VA – 2 violations:
    • Failed to demonstrate through appropriate studies that aseptic processing areas are able to provide adequate protection of the ISO 5 areas in which sterile products are processed.
    • Firm’s products may be produced in an environment that poses a significant contamination risk.
  • Noven Pharmaceuticals, Inc., Miami, FL – 5 violations:
    • Failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of test methods (21 CFR 211.165(e)).
    • Failed to record and justify any deviations from required laboratory control mechanisms (21 CFR 211.160(a)).
    • 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).
    • Failed to maintain written records so that data therein could be used for evaluating, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures (21 CFR 211.180(e)).
    • Failed to follow adequate written procedures describing the handling of all written and oral complaints regarding a drug product including provisions for review by the quality control unit of any complaint involving the possible failure of a drug product to meet any of its specifications and, for such drug products, a determination as to the need for an investigation in accordance with 21 CFR 211.192 (21 CFR 211.198).
  • The Wellness Center Pharmacy, Inc., (dba Designer Drugs), Chattanooga, TN – 3 violations:
    • Firm does not receive valid prescriptions for individually-identified patients for a portion of the drug products produced.
    • Firm failed to demonstrate through appropriate studies that hood is able to provide adequate protection in the ISO 5 area in which sterile products are being produced.
    • Firm produces drug products containing domperidone.
  • Zhejiang Medicine Co. Ltd. Xinchang Pharmaceutical Factory, Shaoxing, China – 3 violations:
    • Failed to have laboratory control records that include complete data derived from all tests conducted to ensure compliance with established specifications and standards.
    • Failed to exercise sufficient controls over computerized systems to prevent unauthorized access or changes to data, and failure to provide adequate controls to prevent omission of data.
    • Failed to record activities at the time they are performed.
  • Adamson Analytical Laboratories, Inc., Corona, CA – 3 violations:
    • Failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
    • Failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
    • Failed quality unit to ensure that materials are appropriately tested and the results are reported.

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