The US Food and Drug Administration (FDA) has sent yet another letter to an India-based pharmaceutical manufacturer alleging inadequate controls to prevent the falsification of testing data-at least the ninth such letter sent in the last year.
As Regulatory Focus has previously explained, FDA has been in the midst of a crackdown against deficient manufacturing practices in India, where inspectors have discovered glaring problems and even outright fraud.
Since 2013, FDA has issued at least eight Warning Letters to Indian companies alleging improper data controls:
FDA has also sent several Form 483s, the precursor to most Warning Letters, to Indian companies such as one to Ranbaxy in January 2014.
The letters stick out because unlike manufacturing deficiencies, data integrity issues strike at the very core of good regulation. If FDA is unable to rely upon the data it is given, how can it ensure that drugs are safe, effective or manufactured to appropriate quality standards?
As most of these Indian manufacturers are now finding out, FDA isn't keen on trusting companies if it can't verify regulatory compliance. Most, if not all, of the above referenced companies are now subject to FDA import alerts that prohibit the import into the US of products manufactured at the facilities until FDA determines that changes have brought the facilities into compliance.
More Data Issues
But even as FDA has sent Warning Letter after Warning Letter to Indian companies regarding data integrity issues, some manufacturers seem to not be getting the message.
In the latest Warning Letter, sent on 27 February 2014 to Canton Laboratories (FEI # 3003297374), a Vadodara-based active pharmaceutical ingredient (API) manufacturer, FDA investigators allege that the company's data controls were inadequate.
In a now-frequent observation, investigators said they found that the company's laboratory analysts were able to "delete and overwrite" raw data, and lacked "sufficient controls to prevent unauthorized access to, changes to, or omission of data files and folders."
"This is especially concerning because our inspection uncovered only 38 raw data files on the hard drive of the AAS, while analysts stated that the AAS had been used for over 400 analyses," FDA wrote. Agency officials were unable to find that data elsewhere, and said that the results for hundreds of analyses were now in doubt.
"Your firm's improper control over the laboratory records raises concerns about the quality of the APIs your firm has released."
In other cases, Canton appeared to have pulled results out of thin air. FDA said it found that the company had reported microbial limit testing for three API batches "without performing [the] tests."
"While your CoAs state that microbial limits conformed to specifications, the inspection found that no testing was done," FDA wrote. "Multiple personnel confirmed that your firm did not perform the microbial tests reported on the CoAs."
Other deficiencies allegedly found during the inspection included improperly cleaned equipment, APIs manufactured using incorrect starting material calculations, missing information in reports, and failure to properly handle consumer complaints.
Failure of 'Basic Responsibility'
But ultimately, it was the data deficiencies that irked FDA the most.
"Our inspection revealed serious documentation practices and reported missing raw data. These deficiencies compromised the quality and accountability of your APIs in the supply chain by reporting that your APIs were in conformance to specifications on your CoAs, when tests were not being conducted," FDA wrote. "It is a basic responsibility of your quality unit to ensure that all API lots produced meet specifications that they are purported to possess."
Those deficiencies "raise serious concerns regarding the integrity, reliability and accuracy of the data generated and available at your facility."
FDA said that until the deficiencies were corrected, it would withhold approval of any new drugs made with its APIs, and also refuse admission to its products if they try to enter the US.
The company's website lists major pharmaceutical manufacturers including GlaxoSmithKline, Baxter, Wyeth, Bausch & Lomb, Pfizer and Mallinckrodt among its clients. It is not clear which, if any, companies have APIs currently manufactured at its India site.
Canton Labs Warning Letter