Ongoing severe Quality Deficiencies lead to regulatory Action - Part 1

After a first Warning Letter from 04 February, 2019, the FDA has issued the second Warning Letter within six months to US company Akorn on 13 June, 2019. With ten pages, it is unusually comprehensive. FDA Warning Letters always reference the relevant chapters of 21 CFR Part 211. In this case, vast deficiencies were found.

Deficiencies concerning various chapters

Your 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).

Here, investigations into OOS laboratory results and manufacturing deviations have been rated as

  • inadequate and incomplete,
  • containing no scientifically sound conclusions,
  • lacking immediate CAPA actions.

Your firm 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)). Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).

In this area, the following deficiencies were found during the inspection:

  • data could be altered and deleted from various laboratory instruments,
  • there was no back-up for standalone instruments,
  • the database, usage logs, and audit trails had been deleted from a high accuracy particle counter instrument,
  • laboratory records did not include signatures,
  • employees had full administrator access to Windows files on an FTIR computer, enabling them to delete, alter or copy data.

Your 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).

On this issue, the following complaints were made:

  • the batch record did not include the leak of a lidocaine hydrochloride solution during aseptic filling operations,
  • the investigation into the low yield for this filling did not take this leakage into consideration,
  • significant filling machine interventions had not been mentioned in the batch record,
  • Quality assurance personnel did not evaluate the interventions recorded in the Mechanical Support Use Logbook.

Your firm failed to follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

This issue will be discussed separately in part 2 of this article.


For these numerous GMP deficiencies, the FDA expects a comprehensive list of corrective measures to be taken in response to the Warning Letter. Until these measures have been implemented, the FDA will not process any pending marketing authorisation applications by the manufacturer. The FDA emphatically reminds Akorn of their cGMP responsibility and that deficiencies found during internal audits must be corrected. Therefore, the company has been imposed to evaluate their quality assurance program audits and inspections of the past five years. The company is to show in writing that corrective measures are being taken for deficiencies found during such audits. If such corrective measures have not been taken, a timetable for the complete processing of all deficiencies is to be drawn up. This timetable is to be signed off by the company's CEO.

Due to the second Warning Letter in such short time, the FDA criticised Akorn's lacking management oversight. It is pointed out that the executive management is responsible for cGMP compliance and that the company is to immediately adjust their global manufacturing operations to comply with FDA requirements.

Sources: Warning Letter to Akorn Inc. from 13 June, 2019 and Warning Letter to Akorn Inc. from 04 February, 2019

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