FDA Cites Data Integrity Issues in All 8 Warning Letters to API Makers

December 4, 2015

The FDA issued eight warning letters to active pharmaceutical ingredient manufacturers during fiscal year 2015 — all of them to non-U.S. companies and all for data integrity issues.

Of the eight, three went to Indian API makers, two to Chinese companies and one each to entities in Thailand, Canada and the Czech Republic. The most recent warning letter, issued in October, went to Gujarat, India-based Pan Drugs Limited.

In fiscal 2014, 11 of the 19 FDA warning letters issued to foreign manufacturers dealt with data integrity. Each letter singles out unauthorized access or changes to data and failure to prevent data omission. Other oft-cited issues include failure to maintain complete data derived from all testing and destruction of original records.

Many of the issues can be traced to the companies’ quality assurance units. The warning letters note problems, including failure of the quality unit to ensure materials are appropriately tested and the results reported, lack of appropriate controls for batch records and lack of controls for documentation.

Data Integrity Issues

In fact, data integrity forms the basis of cGMP for pharmaceutical quality, so when FDA investigators find data integrity issues during an inspection, they always expect other problems as well, an FDA compliance officer says.
Fixing data integrity requires a change in company culture, says Paula Katz, with the Office of Compliance’s Office of Manufacturing Quality. She suggests five steps drugmakers should take when they land in hot water for data integrity issues:

  1. Complete a comprehensive evaluation of data systems;
  2. Undertake risk assessment and assessment of product quality;
  3. Establish a management strategy;
  4. Carry out that strategy; and
  5. Ask for a reinspection.

The agency also urges firms to hire a third-party consultant with expertise in data integrity and cGMP issues, according to Katz, who spoke at the FDA/Product Quality Research Institute conference on advancing product quality. Companies should review their entire organizational structure and personnel responsibilities, Katz says, adding the tendency is to shift blame to a few people directly responsible for data instead of looking for systemic issues.

The FDA also wants to see detailed management strategies and procedures for getting at root causes of data integrity practices affecting the quality of drug products. Management strategies should include details of the drugmaker’s global CAPA and an enhanced ethics program.

Katz urges drugmakers to be proactive and approach the FDA if they think they have integrity issues, as the agency is much more willing to help if they do.

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