Carcinogens in drug: US FDA seeks full re-evaluation in all Aurobindo units

Firm may have a tough task ahead improving manufacturing practices across the board through remediation running into months and years

The generalisations drawn and operation-level observations made by the US Food and Drug Administration (US FDA) in its warning letter to Aurobindo Pharma, over the deviations at the company's active ingredient(API) Unit XI in Srikakulam district, go much beyond the problem of valsartan impurities. They are, in fact, contrary to what the company management believed till it got the letter dated June 20 recently.

Most of the corrective action prescribed by the US drug regulator requires a complete re-evaluation of Aurobindo's manufacturing operations, and is not just limited to the unit currently under radar. As a result, Aurobindo may have a painstaking task ahead to improve the quality of manufacturing practices across its units through remediation running into months and years.

"Provide a thorough, independent assessment of your overall system  for investigating unknown peaks, deviations, discrepancies, out-of-specification(OOS) results, complaints, and other failures. In addition, provide a retrospective review of all distributed batches within expiry to determine, if your firm released batches that did not conform to established specifications, official compendium, or appropriate manufacturing standards," were the sweeping instructions US FDA gave to the company as part of the corrective steps needed to come out of regulatory restrictions.

It may be recalled that the company management had attributed the compliance-related problems in Unit X1 to hypertension product valsartan, which was withdrawn from the market last year, owing to carcinogenic nitrosomine impurities in the drug.

"Because your methods, facilities, or controls for manufacturing, processing, packaging, or holding do not conform to CGMP (current good manufacturing practices), your APIs are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act, 21 USC 351 (a) (2)(B)," the letter stated, while identifying various failures and deviations with regard to manufacturing of valsartan API.

Besides making critical observations on the Srikakulam unit, the US drug regulator reminded the company that it had made similar CGMP observations at other facilities, such as Unit l and Unit lX,  and these facilities were also considered to be in an unacceptable state of compliance with regards to CGMP.  "These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs are inadequate," the letter said.

Aurobindo management requires to respond to these observations within 15 working days also specifying what it has done to correct the said deviations and to prevent their recurrence.

Further the US FDA asked the Aurobindo management to engage a consultant qualified to evaluate the its operations, suggesting a comprehensive review of its operations across the board. 

It may be recalled that Dr Reddy's Laboratories, another Hyderabad-based drug major, faced prolonged regulatory scrutiny in the light of a similar warning letter issued by US FDA to three of its facilities back in November 2015. It took more than three years to sort out all the issues raised by the FDA inspectors, by undertaking multiple remediation efforts across all the facilities of the company.