The FDA posted 4 warning letters this week — 2 of which were GMP letters to drug firms. One firm manufactures APIs and the other manufactures finished pharmaceuticals. We address both below.

DRUGS:

  • Kyowa Hakko Bio Co., Ltd (Yamaguchi, Japan) received a warning letter on August 10th 2018 based on the outcome of an inspection ending September 8th 2017. The firm manufactures APIs. Milva E. Melendez was the sole FDA investigator for this inspection. The 2 deficiencies address serious problems in data integrity and data governance. The firm received the ‘long version’ of the Data Integrity Remediation requirements to which they must respond. Deficiencies include but are not limited to:
    • The Quality unit did not exercise their responsibility. The firm retested and manipulated data after obtaining OOS results. The firm attributes the root cause of these actions to a “lack of awareness of the seriousness” of the actions and to an “environment where test data could be easily manipulated.”
    • The firm failed to exercise adequate controls over computer systems. Some HPLCs did not have audit trail capability (or audit trails enabled), and unique usernames and passwords were not required to access the systems. Annual product reviews included results calculated using unprotected worksheets that were not secured.

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  • Hangzhou Karic Commodities Co., Ltd (Hangzhou, Zhejiang, China) received a warning letter on July 31st, 2018, based on the outcome of an inspection ending March 29th, 2018. Robert J. Martin was the sole FDA investigator. The firm manufactures OTC drug products as a contract manufacturer.
    • FDA states “In your response, you acknowledged the significance of the CGMP observations; however, you provided limited corrective actions and did not provide sufficient detail and evidence to support that your proposed corrective actions will bring your operations and distributed drug products into compliance with CGMP. In your response you also stated that you are “a cosmetics manufacturer, [and you] . . . have no intention of making any drug products,” and that you will work with your client to update your product labels.”
    • FDA strongly recommends the company employ qualified consultant(s) to assist them in coming into GMP compliance. The firm was placed on import alert 66-40 on July 16th, 2018. The GMP deficiencies include but are not limited to:
      • The firm released drug products without adequate testing for identity and strength of active ingredients.
      • The firm failed to test incoming raw materials but relied on data from the suppliers’ CoA without validating the suppliers’ results.
      • The firm initiated a deviation when they observed that the primary packaging of a reserve sample changed color. While the investigation determined that the supplier of primary packaging provided an incorrect raw material, they did not determine whether other lots were impacted by the use of this incorrect material.
      • The firm did not validate the manufacturing process and did not have an ongoing program for monitoring process controls.
      • FDA reminds the company that, as a contract manufacturer, they must manufacture drugs in conformance with GMP and that they are responsible for drug quality regardless of any quality agreements that may state otherwise.

COMPOUNDING PHARMACY:

This week we saw 2 untitled letters posted that we include below.