API and IP Newsletter
Contents
DMFs filed in October 2022
We monitor DMFs filed by Indian companies. FDA publishes list of DMF filers every quarter, the new list of DMF filers in last quarter of year 2022 was published recently.
This week we analysed DMFs filed in the month of October 2022. About 60 DMFs filed in the month of October and about 32-33 DMFs filed by Indian companies.
Some of our observations are as below.
General information
Separate funds for R&D, formulation, API: What pharma sector expects from Union Budget 2023
According to a recent EY FICCI report, in the wake of a growing consensus over providing new innovative therapies to patients, the Indian pharmaceutical market is estimated to touch $130 billion in value by the end of 2023. Meanwhile, the global market size of pharmaceutical products is estimated to cross the $1 trillion mark in 2023. Hence, it is essential to allocate separate funds for R&D, formulation, and API (active pharmaceutical ingredients).
News here.
Spectrum Epinephrine Bulk API Powder recall
Spectrum Laboratory Products, Inc. has issued a nationwide recall for three lots of Spectrum Epinephrine (L-Adrenaline) USP over discoloration concerns. The affected pharmaceuticals may pose mild to severe health risks when administered to a patient.
The voluntary recall was initiated after the company received consumer complaints stating that the Epinephrine (L-Adrenaline) USP drug showed signs of discoloration. The products under the recall fall in the category of Powders for injection (PIs) drugs and are distributed in 'powder' form in vials.
News here.
Intellectual Property
SANDOZ INC., Appellant, v. XAVIER BECERRA, IN HIS OFFICIAL CAPACITY AS SECRETARY OF HEALTH AND HUMAN SERVICES, ET AL., Appellees.
Teriflunomide (Aubagio) belongs to the group of medicines called Immunomodulatory agents. It is used in adults and in children (aged 10 years or older) to treat relapsing remitting multiple sclerosis.
As per public domain information, though it is bit dated, where IQVIA sales data for the 12-month period ending September 2018 was approximately $1.6 billion.
Innovator is Sanofi-Aventis
OB listed patents of Teriflunomide are as below.
Sandoz sought approval for a generic Aubagio.
Sandoz argued, when the FDA approved Aubagio on 12 September 2012, it was implied that it had not previously approved teriflunomide in any other drug hence Aubagio was eligible for an NCE exclusivity.
In view of this generic manufacturers could not submit ANDAs corresponding to Aubagio until 12 September 2016, that would have been an NCE-1 date.
However, Sandoz challenged the exclusivity period and submitted a letter to the FDA on 31 August 2016, arguing that the agency had previously approved teriflunomide and that Aubagio was therefore is not eligible for NCE exclusivity.
Sandoz submitted, leflunomide (Arava) was approved by FDA in 1998 and upon storage it breaks down into teriflunomide (Aubagio).
The FDA characterized teriflunomide as an "impurity" and allowed Arava to contain up to 3.5 percent teriflunomide.
Sandoz argued that the small quantities of teriflunomide that build up in Arava contribute to the functioning of the drug, and that teriflunomide was "physically present as a bioavailable and physiologically/pharmacologically active component" of Arava.
Sandoz contended that the FDA had "approved" teriflunomide when it approved Arava and therefore that the FDA should rescind NCE exclusivity for Aubagio, which used teriflunomide as its active ingredient.
While the FDA considered Sandoz's request to rescind Aubagio's exclusivity, Sandoz submitted two ANDAs for its generic teriflunomide product, each with a paragraph IV certification: one on 7 September 2016, in advance of the four-year deadline, and one on 12 September 2016, ie exactly on NCE-1 date.
Whether Sandoz would enjoy sole exclusivity, or would share exclusivity with other ANDA filers, would be determined by whether Aubagio was properly classified a new chemical entity.
Because Sandoz was the only generic manufacturer to file ANDA prior to the four-year deadline, it would qualify as the only first applicant if FDA rescind Aubagio's four-year exclusivity term.
Sandoz would thus enjoy 180 days of sole exclusivity.
On the other hand if the FDA rejected Sandoz's request, the first ANDA would be premature and Sandoz would have to share first applicant status with some twenty generic applicants who all filed on NCE-1 date ie on 12 September 2016.
In June 2018, the FDA rejected Sandoz's request to rescind Aubagio's NCE exclusivity.
Under the agency's longstanding interpretation of the exclusivity provisions, an ingredient is "approved" in a new drug application only if it was an active ingredient in that drug.
FDA concluded it had recognized teriflunomide simply as an impurity in Arava, not as an active ingredient. Aubagio was properly granted a four-year period of exclusivity, the FDA rejected Sandoz's first ANDA as premature.
Sandoz appealed. In the appeal Sandoz argued that Arava was a "combination drug product containing both leflunomide and teriflunomide" as active ingredients. The FDA denied this appeal on 12 February 2021, affirming its prior reasoning and again concluding that leflunomide was the only active ingredient approved in Arava.
Sandoz filed suit at the District of Columbia, alleging the FDA's decision to maintain NCE exclusivity for Aubagio NCE exclusivity for Aubagio was not in accordance with law.
The judge at the District of Columbia stated, “in effect, Sandoz asks this court to modify the FDA’s Arava approval from 1998 to include teriflunomide as an additional active ingredient despite the fact that Arava’s application, clinical trials, approval, and labelling all considered leflunomide as the only active ingredient”.
The judge declined Sandoz’s invitation to rewrite the FDA’s drug approval decision decades after the fact.
The Court opined, the FDA properly examined leflunomide as the active ingredient in Arava and considered teriflunomide only as an impurity. NCE exclusivity was therefore appropriate for Aubagio, which was the first drug to use teriflunomide as an active ingredient.
Consistent with the statutory and regulatory requirements for new drug approval, the FDA’s approval of a new drug includes approval of the drug’s active ingredient, but not its impurities.
When the FDA approved Arava, it recognized teriflunomide as an impurity and hence did not approve it within the meaning of the FDCA (Federal Food Drug and Cosmetic Act).
Teriflunomide was approved for the first time as the active ingredient in Aubagio, which properly received NCE exclusivity.
Because Sandoz’s challenge fails, its generic equivalent will not benefit from a period of sole marketing exclusivity of 180 days. The judgment of the district court is affirmed.
Decision here
