FDA investigators are finding unprecedented data integrity problems at contract and active pharmaceutical ingredient manufacturers, even after they have been audited by the firms that hired them, an FDA official said.

“It is apparent to us that industry audits do not always spend much time, if any, looking at the integrity of data,” said Richard Friedman, associate director of CDER’s Office of Manufacturing and Product Quality.

Data integrity violations, such as backdating production records or fabricating laboratory data, causes the agency to question all of the data generated by a facility, and can lead to applications being rejected, he said. In fact, “in several cases, sponsors have withdrawn their applications due to data integrity problems,” Friedman said at the FDAnews Inspections Summit in Bethesda, Md.

Making data integrity a component of the audit is imperative for any auditing program, Friedman said. “Audits are done to assess a potential business partner’s capability. If the data and information that a manufacturer provides to you is not trustworthy, how can you evaluate their capability?” he said.

The fallout from the FDA finding a data integrity problem in a preapproval application can extend far beyond the drug under review, said Steven Niedelman, lead quality system and compliance consultant with the law firm King & Spalding. Once the FDA becomes suspicious of a supplier, the agency may review all of the products its components are used in, triggering enforcement actions including 483s and warning letters.

The FDA has made data integrity a high priority during inspections after a spike in findings at international facilities, and Friedman suggested that drugmakers do thorough background checks to look for red flags when considering a supplier or contractor.

“If there is no record of that firm, or if it resides in a country that has an immature regulatory system, it may be particularly advisable to look at whether or not the company has the right systems in place to ensure that all data coming out of operations has integrity,” he said.

Drugmakers also should check a supplier’s internal audits for any data integrity issues, said John Avellanet, managing director and principal at the consulting firm Cerulean Associates.

A red flag is how the supplier conducts the internal audit itself. Avellanet said two key problems to look for are companies that restrict an auditor’s access to all needed data, or narrows the scope of the audit. If these practices are evident at one of your suppliers, “you can immediately know they don’t have a good internal audit program, which calls into question the other controls they claim to have,” Avellanet said.

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