US judge blasts FDA 'telephone game', but upholds action against Ranbaxy
This article was originally published in Scrip
US district judge Beryl A Howell has made a series of stinging observations against both Ranbaxy and the FDA in a case concerning the Indian firm's rescinded tentative approvals for generic versions of Valcyte (valganciclovir hydrochloride) and Nexium (esomeprazole magnesium).
Decimating some of Ranbaxy's arguments, Judge Howell referred to how the Indian firm managed to "deceive and pressure" the FDA into erroneously granting tentative approval to its ANDAs, but she did not have too many kind words for the FDA either.
In a 71-page interim redacted opinion dated 11 March in the case in the US District Court of Columbia, Judge Howell noted that the agency had demonstrated that its internal system of checks and balances failed to prevent "serious errors" with at least five of Ranbaxy's ANDAs, including for Valcyte and Nexium. Worse still, the very employees who were tasked with reviewing manufacturers' applications to ensure compliance with the industry's best practices were granting approval "without knowing why, using language they did not understand".
At one point, the judge's opinion referred to the process by which the FDA considered certain Ranbaxy ANDAs for tentative approval as reminiscent of a "child's game of telephone", where the initial message becomes "distorted upon repetition".
At another place, Judge Howell said by late 2007, the CDER [Centre for drug Evaluation and Research] and OGD [Office of Generic Drugs] employees involved in making these decisions were apparently no longer considering why an exception to Ranbaxy's compliance hold should be granted. Instead, they were merely "cutting-and-pasting" language from previous emails pertaining to other ANDAs recommending that OGD issue tentative approval despite the compliance hold.
"A series of agency errors combined with the plaintiffs' malfeasance led to the tentative approval of the ANDAs for generic drug products for esomeprazole and valganciclovir," the judge said.
Judge Howell, however, underscored that even though that error was "belatedly" corrected, the FDA has the inherent authority to correct its mistakes. She also opined that the agency's interpretation of the statutory provision requiring forfeiture of 180-day generic marketing exclusivity rights if the first ANDA applicant is found not to have met the requirements for tentative approval within 30 months of an ANDA's submission was "reasonable".
Ranbaxy's arguments
Ranbaxy had, in a string of arguments, claimed that the FDA's decision was contrary to the plain text of the concerned US regulation which it believes does not authorize the agency to decline to issue tentative approval for an ANDA because the facility in which the drug is to be manufactured is out of compliance with cGMP.
At one point the Judge, however, noted that by Ranbaxy's logic, an applicant could state in its ANDA that it planned to manufacture a generic drug in an "outhouse behind the applicant's house using a child's chemistry set", and the FDA would have no power to deny tentative approval to that application on the grounds that the applicant could never, as submitted, be granted final approval since the application does not comply with cGMP.
Ranbaxy also claimed that the FDA had "consciously" adopted the firm's interpretation of the statute when it considered whether to issue tentative approval to the ANDAs at issue and had now changed its policy.
Ranbaxy declined comment on the specifics of the 11 March opinion and referred to its 3 March notice to the Bombay Stock Exchange. Ranbaxy, which is in the process of being acquired by Sun Pharma, had then acknowledged that the court had issued an opinion indicating that it was denying Ranbaxy's request for preliminary injunction and was granting the FDA's requests for summary judgment on the merits.
"In effect, the Court's decision upheld the status quo that FDA had created by rescinding Ranbaxy's tentative approvals and forfeiting our 180 day exclusivities on valganciclovir and esomeprazole in November 2014," the company said.
The indications are that the Indian firm has appealed the district court verdict, though this could not be immediately confirmed.
case history
The FDA in November last year rescinded the tentative approvals for Ranbaxy's generic Nexium and Valcyte saying that these were in error because of the "compliance status" of Ranbaxy's facilities referenced in the ANDAs at the time the approvals were granted (scripintelligence.com 7 November 2014). Dr Reddy's Laboratories and Endo International then received approval from the agency for generic Valcyte.
Ranbaxy later challenged the yanking of tentative approvals for the products (scripintelligence.com 18 November 2014).
In January this year, the US FDA approved the first generic version of AstraZeneca's Nexium (esomeprazole magnesium delayed-release capsules) from Teva arm Ivax Pharmaceuticals (scripintelligence.com 27 January 2015).
Ranbaxy had earlier in its motion for expedited ruling on pending motions dated 26 January before the district court said that it was renewing its request for preliminary injunctive relief and urged the court to "promptly" issue its disposition in this matter – "either granting the company the relief it had requested (which would stem the mounting damages Ranbaxy was incurring from FDA's unlawful action) or denying that relief promptly (so that Ranbaxy can continue pursuing its claims on appeal)".