Improving Regulatory Transparency for New Medical Therapies Act

A new act passed in the U.S. House of Representatives: What will it protect? Patent exclusivity, non-patent exclusivity, or both? Anything else also it deals with?

The bill titled ‘A bill to amend the Controlled Substances Act with respect to drug scheduling recommendations by the Secretary of Health and Human Services, and with respect to registration of manufacturers and distributors seeking to conduct clinical testing, and for other purposes’ was passed on March 16^th, 2015, in the U.S. House of Representatives, by voice vote H.R. 639, for an act which may be cited as ‘‘Improving Regulatory Transparency for New Medical Therapies Act’’.

The first comment which I give on this bill is, it will protect both Patent exclusivity and non-patent exclusivity in case of New Chemical Entities (NCEs) which that required scheduling decisions by the Drug Enforcement Administration (DEA) under the Controlled Substances Act (CSA) before the drug products could be placed on the market. How? Before I explain this, I would like to take you with me to the events in the recent past, which made it essential to pass this bill.

But even before that read this:

Form FDA 356h without which NDA applications for controlled substances can’t be filed with FDA prevents commercial marketing for controlled substances till they are scheduled by the DEA under the CSA, developers of controlled substances claim. If this is the case, what happens if FDA approves NDA before they are scheduled under CSA? When all important NCE exclusivity is triggered for that NCE? On the date of NDA approval by the FDA itself? Or FDA waits till they are scheduled under CSA? Let’s find out what the FDA should do on this (and also what it has done before). Let’s unravel to the past.

For three drug products having controlled substances as the Active Pharmaceutical Ingredient, Lacosamide tablets (VIMPAT, NDA no- N022253, approval date- October 28, 2008) by UCB INC and Perampanel tablets (FYCOMPA, NDA no- N202834, approval date- October 22, 2012) and Lorcaserin HCl tablets (BELVIQ, NDA no- N022529, approval date- June 27, 2012) by EISAI INC, NCE exclusivity was triggered by FDA on the date of approval. Yes, even before UCB INC and EISAI INC could place the drug on the market. For three products referred above dates on which they could be actually be marketed were June 09, 2009, January 02, 2014, and June 07, 2013, respectively. This led to UCB INC and EISAI INC filing citizen petitions to FDA, petition numbers FDA-2013-P-1397-0001 and FDA-2013-P-0884-0001 respectively. This was not surprising because (erroneous) triggering of NCE exclusivity before one can market the drug was leading to a reduction in the all valuable NCE period. For a blockbuster drug, this can lead to significantly high monetary loss. Though I do not intend to discuss the importance of NCE exclusivity in-depth here, would like to appreciate the importance of the same by drawing your attention to the fact it is the only exclusivity (amongst both patent and non-patent exclusivities) which blocks submission of ANDA and 505 (b) (2) applications at least for four years once it is triggered (those who knew this, please consider it as a reminder). It means shortening of NCE exclusivity caused due to erroneous triggering can lead to the early entry of generics into the market. In fact, in the case of Lacosamide, the shortening of NCE exclusivity has lead to the early filing of ANDA applications for its generic version.

In the petition dated July 25, 2013, filed by Eisai, it requested FDA to trigger NCE exclusivity only when FDA approves labeling incorporating the final schedule permits commercial marketing of the products. It also claims that FDA’s letters approving the products as safe and effective reinforce this requirement, stating “when the scheduling is finalized, you will need to make appropriate revisions to the package insert, the patient package insert and the carton and the immediate-container labels through supplementation of your NDA”.

Further in its petition, Eisai provided two solutions to resolve the issue at hand:

1. First what FDA can opt is, if a Changes Being Effected (“CBE”) supplement is used to reflect DEA’s scheduling decision, “the day the CBE supplement is submitted with the necessary label changes is the day the sponsor can commercially market the product, and accordingly, should be the date for triggering the NCE exclusivity period, or
2. FDA could determine that the date for triggering the NCE exclusivity period is the date the DEA scheduling order becomes effective as this is the date when a CBE supplement could be submitted to permit the sponsor to commercially market the product.

And in the petition dated November 18, 2013, UCB adopted the same rationale and requested the FDA to start the clock running on the NCE exclusivity from the date which it could actually enter the market.

In reply, FDA issued Citizen Petition Denial Response dated April 30, 2014, to Eisai and UCB, being firm by its stand that NCE exclusivity will be triggered only on the date at which FDA approves NDA. In doing so it gave a reference of § 505(j)(5)(F)(ii) which deals with ANDA applications and § 505(c)(3)(E)(ii) (505(b)(2) which deals with 505(b)(2) application, which provides for the start of NCE on the date of the approval.

What followed this is, Eisai filed suit dated August 08, 2014, Eisai filed a Complaint in the U.S. District Court for the District of Columbia alleging that the FDA erroneously triggered periods of 5-year NCE exclusivity for its two products at issue.

Meanwhile aggrieved by the slow speed of DEA to provide scheduling decisions, Eisai filed a petition to Order Scheduling of FYCOMPA on August 19, 2013, which was denied by the U.S. Court of Appeals for the D.C. Circuit on October 22, 2013.

While litigation between Eisai and FDA is still pending, the bill “Improving Regulatory Transparency for New Medical Therapies Act” has been passed, which was first introduced on February 2, 2015.

This act with three sections has amended Section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355), Section 351 of the Public Health Service Act (42 U.S.C. 262), Section 512 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b), Section 571(d) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360 ccc(d)), Section 572 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360ccc–1), Section 573(c) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360ccc–2(c)) while dealing with ‘EFFECTIVE DATE OF APPROVAL’. These amendments seem to favor NCE developers. In order to improve practices related to ‘SCHEDULING OF NEWLY APPROVED DRUGS’, this bill has amended Section 201 of the Controlled Substances Act (21 U.S.C. 811). To ensure that no one who deserves patent exclusivity should miss out on it, ‘EXTENSION OF PATENT TERM’ related procedures have also been taken care of in the same section of the act (section no-2) along with ‘EFFECTIVE DATE OF APPROVAL’ and ‘SCHEDULING OF NEWLY APPROVED DRUGS’. Amendments to the 35 U.S. Code § 156 while dealing with ‘EXTENSION OF PATENT TERM’ touch the period during which application for Patent Term Extension may be submitted (within the sixty-day period beginning on the ‘covered date’), the definition of which (covered date) has newly been inserted.

While section 1 gives the title, section 3 offers provisions related to ‘ENHANCING NEW DRUG DEVELOPMENT’ by introducing amendments to Section 303 of the Controlled Substances Act (21 U.S.C. 823).

Once this bill is enacted, we can expect the Orange book page for Perampanel and Lorcaserin HCl to display NCE exclusivities expiring on January 02, 2019, and June 07, 2018, respectively, beginning on the date when they actually could be marketed (unless FDA determines to offer the advantages to only those applicants who file their NDA after the date of the enactment).

About the Author: Swapnil Patil, Patent Associate at Khurana & Khurana, Advocates and IP Attorneys and can be reached at [email protected]