Contract Lab Valisure Relinquishes its Testing Prowess
Contract testing laboratory Valisure has relinquished its regulatory testing ability after a recent FDA inspection raised testing issues associated with the lab, which was behind the identification of several high-profile product safety concerns. The agency has noted that until recently, the company’s Web site offered services including a “certification process” whereby its testing concludes whether drugs received from a manufacturer are “ready for shipment.” Following the inspection, Valisure stated that its testing is “only for informational and marketing purpose and not for any regulatory purpose,” but the agency said in a 12/5-posted untitled letter that it remains concerned that drug manufacturers may rely on the lab’s services in the future to perform contract testing to fulfill GMP requirements.
Valisure, which once described itself as an analytic laboratory, had previously tested and detected high levels of N-Nitrosodimethylamine (NDMA) in specific batches of prescription drug products containing metformin and ranitidine. FDA independently tested the products and found situations where NDMA levels were above safety limits in metformin and subsequent recalls were conducted. A related citizen petition from the lab saw FDA dismissing its testing methodology when it responded, saying the Valisure method had not been appropriately validated to demonstrate specificity for measuring NDMA in metformin.
FDA also cast doubt earlier on Valisure’s methods for evaluating ranitidine, dismissing its one conclusion — that ranitidine turns into the cancer causing impurity NDMA in the stomach — that was not supported by the agency’s testing (see earlier story). FDA followed up with an update at the time saying that preliminary testing on numerous ranitidine products has found NDMA levels that are similar to levels consumers would normally be exposed to in foods like grilled or smoked meats.
During a recent FDA inspection of the contract lab, Valisure explained in its Form 483 response that “passing Valisure testing or obtaining a Valisure certification is not a requirement of drug manufacturing specifications nor FDA approval.” It further said its services are not appropriate for any regulatory purpose. However, FDA said in the untitled letter that it was concerned that entities may still use its test results for GMP purposes, and it summarized scientific deficiencies in the firm’s test methods.
For example, FDA said the Valisure’s 483 response stated that methods are accurate and reliable pursuant to International Organization for Standardization procedures, but it failed to provide any supportive evidence or reports that the methods have been validated, verified, or are suitable for use to support fulfillment of GMP requirements, such as for allowing the release of drugs into interstate commerce.
Additionally, FDA took issue with the firm for not adequately addressing out-of-specification test results; using instruments, apparatus, gauges, and/or recording devices that did not meet established specifications; and failing to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, and other records.
Asked whether FDA’s untitled letter discredited Valisure’s previous testing, an FDA spokesman had this to say to FDA Webview: “While the FDA takes data provided by stakeholders such as Valisure under advisement, and often conducts follow-up investigations as a result of such information, the agency does not recommend recalls or take other compliance actions for drugs based on third-party sample analyses.
“The FDA has independently analyzed certain drugs that Valisure tested,” the spokesman continued. “When the agency analyzed these drug samples using validated testing methods, we found different results than Valisure did, including finding violative results in cases where Valisure had reported that drugs from those firms had passed Valisure’s testing. When the FDA found unacceptable levels of contaminants in drugs that FDA independently tested, we took actions against the manufacturers of these drugs, including via import alerts and Warning Letters. This underscores why the agency must base compliance actions on scientifically sound, validated data that is based on validated test methods and appropriate laboratory controls when regulatory activities are based on drug sample analysis. The FDA continues to monitor the quality of drugs and, when appropriate, encourages retailers to remove products from store shelves and online marketplaces when issues arise.”