FDA chides Valisure for DSCSA, analytical testing issues

Regulatory NewsRegulatory News | 07 December 2022 |  By 

The US Food and Drug Administration (FDA) recently sent an untitled letter to Connecticut-based contract testing lab Valisure for failing to comply with the Drug Supply Chain Security Act (DSCSA) and for findings of “methodological deficiencies” in the company’s analytical testing laboratory.
FDA’s action targets a company that played a role in several recent high-profile recalls after it raised concerns about the levels of possible carcinogenic impurities found in the blood pressure drug valsartan, the heartburn medication ranitidine and the diabetes drug metformin. All three drugs were subject to recalls in recent years due to the detection of nitrosamine impurities. The company also sounded the alarm on benzene impurities in certain hand sanitizers and spray sunscreens in 2021, which eventually lead to multiple recalls.
DSCSA observations
The 5 December letter followed a more than one-month long inspection conducted from May-July 2021 which found DSCSA violations and problems found in the analytical testing laboratory.
The DSCSA observations concerned Valisure’s former online pharmacy, ValisureRx. The issues cited in the letter included failure to investigate suspect product, failure to make determinations of illegitimate products and failure to notify FDA and trading partners of illegitimate product within 24 hours of such a determination.
FDA also noted that company “has never filed an annual report with the FDA as required by section 583(e)(2) of the [Federal Food, Drug, and Cosmetic Act] FD&C Act.”
FDA’s enforcement efforts have rarely focused on DSCSA violations; the last time FDA issued a warning letter in this area was its February 2019 warning letter to McKesson, a drug distributor.
In responding to the DSCSA observations, Valisure said it no longer performs drug dispensing and wholesaling activities, so is not subject to complying with DSCSA requirements. The company said it sold its ValisureRX division which conducted dispensing and wholesaling activities in April 2021.
Testing lapses
In other areas, FDA found problems with Valisure’s testing methods, including the lab’s failure to demonstrate that its analytical methods used to generate Certificates of Analysis (COAs) provided to customers were “suitable.”
For example, the laboratory used FDA’s Gas Chromatography-Mass Spectrometry (GC-MS) method developed for the detection of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in valsartan drug products. The lab also used this method to detect other types of impurities in additional products, though it “failed to validate that this method can adequately detect these additional impurities in the drug products you analyzed.”
The other impurities were dimethylformamide (DMF), N-nitrosoethylisopropylamine (NEIPA), N- nitrosodiisopropylamine (NDIPA) and N-nitrosomethylethylamine (NMEA).
The firm also failed to adequately handle out-of-specification (OOS) test results. For example, following the failure of Inductively Coupled Plasma Mass Spectrometry (CP-MS) lead analysis, the firm “changed the tube digestion procedure and re-analyzed the sample without performing an OOS laboratory investigation or determining that the second digestion and re-analysis procedure were appropriate.”
Additionally, FDA said the firm failed to exercise appropriate controls over computer equipment. “While the software controlling your analytical equipment requires unique user accounts and passwords, your analysts log into the operating computers using a generic administrators account such as ‘Valisure’ or ‘Valisure Lab.’”
Valisure only tests for informational purposes
In response to FDA, Valisure said its testing activities are “only for informational and marketing purpose and not for any regulatory purpose,” and is not “subject to the cGMP standards set forth by FDA.” However, FDA said it is concerned that other entities will use its testing for cGMP purposes.
Valisure did not respond to requests for comment from Regulatory Focus.
Valisure has acted as a consumer safety watchdog in performing independent testing of drugs and notifying the public of potential safety issues when problems are found. In September 2020 the company filed a citizen petition indicating that lots of metformin had high impurity levels and requested that FDA recall lots of affected drugs. (RELATED: Nitrosamine detection tests should be ‘fit for purpose,’ says FDA, Regulatory Focus 1 November 2021)
Valisure’s CEO David Light has also criticized FDA’s testing methods in June 2020 testimony before Congress, and urged legislators to establish independent laboratory testing of all foreign imported drugs before these product are distributed in the US.
FDA untitled letter


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