The letter focuses on the company’s failure to establish and document the accuracy, sensitivity, specificity, and reproducibility of test methods dating back to FDA inspections from 2009 and 2011.
The previous inspections also found that many methods used by the CRO (contract research organization) to test products “had not been verified or validated. Our current inspection found that methods continued to be validated inadequately, and that some methods cited in the last inspection were still not validated.”
In fact, the FDA found that only four of the fourteen analytical methods identified in the 2011 inspection have since been validated.
As part of its intended corrective actions, Sipra said it would include a disclaimer statement in its validation protocol that “the selected parameters do not fulfill the requirements for complete validation package as per Sipra’s SOP and ICH guidelines.”
But the FDA slammed the idea, saying it’s “essential for a contract test laboratory to use validated methods to ensure that results of pharmaceutical analyses subject to CGMP [current good manufacturing practice] are accurate.”
The agency also noted that “a disclaimer does not release you from the CGMP requirement to ensure that your test methods are validated and suitable for their intended use…Further, you did not indicate in your response whether you plan to inform your clients that you have not been following your own SOPs on method validation, or that validation packages failed to meet ICH guidelines.”
In addition, the FDA made it clear that it considers contractors as “extensions of the manufacturer’s own facility” and that its clients “must provide you with all of the scientific data and information needed to support reliable method implementation.”
Sipra says its clients include some of the top ten pharma companies, including Novartis, Johnson & Johnson, Sanofi, GlaxoSmithKline and Merck, among others.
As far as the out-of-specification (OOS) test results, the FDA told the company that if the results do not “determine an assignable cause, all test results should be reported to the customer on the certificate of analysis. We also recommend providing your OOS reports to your customers, and including steps in your procedures to obtain critical information from your customers about the products you test that could affect the suitability of the methods you use.”