The Good, the Bad and the Ugly: New Legislation Would Reform the ANDA Suitability Petition Process and Require Timely Assignment of 505(b)(2) NDA Therapeutic Equivalence Evaluation Codes (“the Good”)

April 30, 2021By Kurt R. Karst

Over the past few days there’s been an avalanche of FDA-related legislation introduced in both the U.S. House of Representatives and the U.S. Senate.  Some of the bills introduced are related to a House Judiciary Antitrust Subcommittee hearing, titled “Addressing Anticompetitive Conduct and Consolidation in Health Care Markets,” while others found their way into the Bill Hopper because of a renewed interest in Congress to address drug prices (see a recent U.S. Government Accountability Office report here).

As we perused the bills, we sorted them into three categories: the Good, the Bad, and the Ugly.  Today, we’ll address a couple of bills that fit Clint Eastwood’s role as “the Good” in the 1966 Italian epic spaghetti Western film, “The Good, the Bad and the Ugly.”  In another post or two, we’ll address those that fit the role of Lee Van Cleef as “the Bad,” and Eli Wallach as “the Ugly.”

Both bills – S. 1462, the “Simplifying the Generic Drug Application Process Act,” and S.1463, the “Modernizing Therapeutic Equivalence Rating Determination Act” – were introduced by Senators Bill Cassidy, M.D. (R-LA) and Tina Smith (D-MN) “to speed the development of and improve access to lower-cost generic drugs” by making changes to the FDC Act and 505(b)(2) NDA approval pathway, “which will make it easier for generics to come to market driving up competition and driving down drug prices,” according to a press release announcing the introduction of the bills.  While we’re pretty excited about the changes both bills would make to the law, we’re particularly stoked about S. 1462, the “Simplifying the Generic Drug Application Process Act.”

Simplifying the Generic Drug Application Process Act (S. 1462)

For years we’ve been critical of FDA’s ability (or rather, inability) to timely rule on ANDA Suitability Petitions.  Suitability Petitions permit the submission of an ANDA that differs from an NDA-approved listed drug in strength, dosage form, route of administration, or active ingredient (in a combination drug).  But until FDA approves a Suitability Petition, an ANDA cannot be submitted to the Agency for the proposed change.  Although the statute requires FDA to approve or reject a Suitability Petition within 90 days of receiving the petition, FDA very, very rarely meets that deadline.  Instead, FDA takes several years to rule on a Suitability Petition, by which time there may no longer be much of any interest (or value) in marketing the proposed generic drug product.  Indeed, back in 2014, we put together a review of more than 1,300 ANDA Suitability Petitions submitted to FDA since the enactment of the 1984 Hatch-Waxman statutory provision creating them.  That analysis (here) shows that FDA has been largely unable to meet the mandatory statutory 90-day goal of approving or disapproving a petition.

Despite FDA’s historical policy of not ruling on ANDA suitability petitions within the statutory deadline, leading to a loss of faith in the process itself, FDA, in August 2013, published a Manual of Policies and Procedures (“MaPP”) – FDA, Manual of Policies and Procedures, Office of Generic Drugs: ANDA Suitability Petitions, MaPP 5240.5 (Aug. 21, 2013) – establishing the policies and procedures for responding to suitability petitions, and that reiterates that “[u]nder 21 CFR 314.93(e), the Agency will approve or deny the petition no later than 90 days after the petition is submitted.”  According to the MaPP:

[The Office of Generic Drugs’ (“OGD’s”)] goal is to respond to suitability petitions in an efficient and effective manner.  To meet this goal, a number of parties within the Center for Drug Evaluation and Research (CDER) and throughout the Agency must work in a coordinated manner.  OGD, the office primarily responsible for responding to suitability petitions, has developed procedures for enhancing communication among parties involved in addressing the request(s) in the suitability petitions.

Unfortunately, in the nearly eight years since FDA issued MaPP 5240.5, little progress has been made.  Curiously, the most recent version of MaPP 5240.5 omits any discussion of the 90-day statutory period, as well as to OGD’s goal to respond to suitability petitions in an efficient and effective manner.

Perhaps as a result of FDA’s failure to timely address suitability petitions, Congress expressed its expectation that FDA meet this 90-day deadline in Section 805 of the 2017 FDA Reauthorization Act (“FDARA”).  In addition to a “Sense of Congress” provision stating that FDA “shall meet the requirement under [FDC Act § 505(j)(2)(C)] and [21 C.F.R. § 314.93(e)] of responding to suitability petitions within 90 days of submission” (FDARA § 805), Congress hoped to encourage FDA to expedite responses to such petitions by requiring a report of the number of outstanding suitability petitions and a report of the number of suitability petitions that remained outstanding 180 days after submission.  In addition, the GDUFA II Performance Goals Letter states that “FDA aspires to respond to Suitability Petitions in a more timely and predictable manner.”

FDA has thus far not complied with this congressional mandate and GDUFA II Performance Goal.  According to FDA’s most recent FDARA § 805 activities report – from Fiscal Year 2020 – 174 suitability petitions are pending a substantive FDA response for more than 180 days from the date of receipt of the petition, and there are 180 suitability petitions pending a substantive FDA response.

That brings us to S. 1462.  According to the press release on the bill:

The Simplifying the Generic Drug Application Process Act repeals section 505(j)(2)(C) of the Food Drug and Cosmetic Act (FDCA) so that sponsors can submit generic drug applications (ANDAs) without the need for the U.S. Food and Drug Administration (FDA) to first grant a suitability petition.  FDCA requires that if a generic drug sponsor wants to submit an ANDA for a drug that differs from the brand in terms of its route of administration, dosage form, or strength, then the generic needs to first submit a suitability petition to FDA requesting permission to file the ANDA.  FDCA requires FDA to respond within 90 days, but if FDA does not respond, the generic cannot file the ANDA.  Unfortunately, FDA has not responded to many suitability petitions filed over the last seven years – preventing submission of ANDAs for drugs in shortage and drugs without generic competition.  This bill repeals the requirement to file a suitability petition for ANDAs that do not require clinical data.  Even with this change, FDA still has the opportunity to review the proposed change to the brand before the ANDA is filed and then again when reviewing safety and efficacy as part of the review process.

That’s right!  Congress has finally given up on waiting for FDA to reform the Agency’s handling of ANDA Suitability Petitions and has wisely decided to step in and reform the system.

Specifically, the bill would amend current FDC Act § 505(j)(2)(C) to allow the submission of an ANDA that differs from the listed drug in dosage form or strengths (i.e., the two most common Suitability Petition changes).  Instead of having to wait (years) for FDA to separately approve a Suitability Petition before submitting an ANDA for the proposed change, the law would be amended such that “[t]he Secretary shall approve or disapprove the submission of such an abbreviated application during the course of its determination whether to receive the application pursuant to [21 C.F.R. § 314.101].”  That is, the current petition process would effectively be collapsed into FDA’s filing (receipt) determination.

This is a fantastic legislative proposal, and one that may truly reinvigorate the historical “petitioned ANDA.”

Modernizing Therapeutic Equivalence Rating Determination Act (S. 1463)

Beginning with the 36th (2016) edition of the Orange Book, the Orange Book Preface was updated to state that “[a] person seeking to have a therapeutic equivalence rating for a drug product approved in a 505(b)(2) application may petition the Agency through the citizen petition procedure (see 21 CFR 10.25(a) and 21 CFR 10.30).”   Since then, FDA has received numerous citizen petitions requesting the assignment of a Therapeutic Equivalence Code (“TE Code”).  In most cases, however, those petitions languish at FDA for an extended period of time (usually years).  In the meantime, 505(b)(2) NDA holders must pay an annual PDUFA user fee for such products and request a refund contingent on FDA’s citizen petition determination.  Prompt TE Code determinations (i.e., either “A” or “B” ratings) for drug products approved under a 505(b)(2) NDA would eliminate these inefficiencies, the costs to the Agency and the generic drug industry associated with those inefficiencies, and would clarify the substitutability of several drug products.

According to the press release on S. 1463:

The Modernizing Therapeutic Equivalence Rating Determination Act requires FDA to assign therapeutic equivalence ratings for 505(b)(2) applications at the applicant’s request, as it does for ANDAs.  The 505(b)(2) approval pathway is used to approve new drugs while leveraging certain data from an already approved drug.  To the extent that the drug candidate differs from the already approved drug, the sponsor has to generate sufficient data including clinical data to support the differences, but does not automatically receive a therapeutic equivalence rating.  A therapeutic equivalence rating is necessary to trigger automatic substitution at the pharmacy level and thus critical to driving competition.  Because 505(b)(2) is technically a new drug pathway, the statute does not require FDA to assign a therapeutic equivalence rating.  Sponsors can request it via the citizen petition process, but this can take significant time.  Requiring FDA to assign a therapeutic equivalence rating for 505(b)(2) applications will level the playing field for 505(b)(2) products to compete with name brand drugs.

Specifically, the bill would amend the statute’s Orange Book provisions FDC Act § 505(j)(7)(A) to require that FDA make a TE Code determination for a 505(b)(2) NDA “at the time of approval of such application or not later than 30 days after the date of such approval, provided that the sponsor requests such a determination in the original application, in a form prescribed by the Secretary.”

Like S. 1462, S. 1463 would make small, but very meaningful, changes to the statute to address and remedy current FDA inefficiencies.  And if there’s one thing this German-blooded American likes, it is efficiency!