Somebody’s Thinking Ahead! New Legislation Seeks Some Clarity as the BPCIA’s March 2020 Transition Deadline Appears on the Horizon

By Kurt R. Karst –      

Last week marked the 5th anniversary of the March 23, 2010 enactment of the Affordable Care Act (“ACA”).  Title VII of the ACA, the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), amended the Public Health Service Act (“PHS Act”) to create an abbreviated licensure pathway for biological products that are demonstrated to be “biosimilar” to or “interchangeable” with an FDA-licensed reference biological product.  Over the past few years, much of industry’s focus has been on FDA’s creation and implementation of the biosimilar pathway (see our previous posts here, here, and here), and on the legal battles over the “patent dance ” provisions (see our previous posts here and here).  But there’s another set of provisions in the BPCIA that folks have begun eyeing with increased interest: the so-called “transition provisions.”  And a new bill introduced last week by Representative Michael Burgess (R-TX), the “Generic Complex Drugs Safety and Effectiveness for Patients Act of 2015” (H.R. 1576), seeks to get the Government Accountability Office (“GAO”) involved in evlauating the provisions before they come into play. 

The transition provisions are at Section 7002(e) of the BPCIA and account for a change made to the statutory definition of “biological product” at PHS Act § 351(i) to include a “protein (except any chemically synthesized polypeptide).”  That change brings into the fold of biologics (and thus biosimilars) regulation a larger grous of products, including several natural source proteins like insulin, hyaluronidase, menotropins, and human growth hormones, that have been regulated as drugs under the FDC Act.  Specifically, BPCIA § 7002(e) states:

(e) PRODUCTS PREVIOUSLY APPROVED UNDER SECTION 505.—

(1) REQUIREMENT TO FOLLOW SECTION 351.—Except as provided in paragraph (2), an application for a biological product shall be submitted under [PHS Act § 351] (as amended by this Act).

(2) EXCEPTION.—An application for a biological product may be submitted under section [FDC Act § 505] —

(A) such biological product is in a product class for which a biological product in such product class is the subject of an application approved under such section 505 not later than the date of enactment of this Act; and

(B) such application—

(i) has been submitted to the Secretary of Health and Human Services (referred to in this subtitle as the “Secretary”) before the date of enactment of this Act; or

(ii) is submitted to the Secretary not later than the date that is 10 years after the date of enactment of this Act.

(3) LIMITATION.—Notwithstanding paragraph (2), an application for a biological product may not be submitted under [FDC Act § 505] if there is another biological product approved under [PHS Act § 351(a)] that could be a reference product with respect to such application (within the meaning of such section 351) if such application were submitted under [PHS Act § 351(k)].

(4) DEEMED APPROVED UNDER SECTION 351.—An approved application for a biological product under [FDC Act § 505] shall be deemed to be a license for the biological product under such section 351 on the date that is 10 years after the date of enactment of this Act. 

Thus, an application for a biological product must be submitted under PHS Act § 351 subject to the exceptions at BPCIA § 7002(e)(2) during the 10-year transition period that ends on March 23, 2020. 

The “Generic Complex Drugs Safety and Effectiveness for Patients Act of 2015” is, at least in part, an effort to get ahead of the curve before BPCIA § 7002(e) comes into play by asking the GAO to study some of the unique challenges presented by FDA’s evaluation of generic versions of complex drug products.  The bill sets out two broad questions for the GAO to consider:

1. With respect to nonbiologic complex drug products that have not been fully characterized . . . , whether the listing of such drugs as reference products in generic drug applications presents unique challenges in meeting approval standards that are significantly different than the challenges presented by generic drug applications that list small-molecule reference products.
2. With respect to biological products that are within the scope of the exception under section 7002(e)(2) of Public Law 111-148 (relating to temporary authority for the approval of biological products under [FDC Act § 505], whether the listing of such biological products as reference products in generic drug applications presents unique challenges in meeting approval standards that are significantly different than the challenges presented by generic drug applications that list small-molecule reference products.

The term “complex drug products that have not been fully characterized” is further defined in the bill to mean a drug for which: (1) the active ingredient has molecular diversity; (2) scientific analytic methodologies are unable to fully identify the molecular structures and physiochemical properties of the active ingredient; and (3) the nature of the active ingredient is not understood sufficiently to identity both the the molecular components of the drug that are involved in producing the therapeutic effect, and the mechanisms of action that produce such effect.

If the GAO determines, after consulting with FDA and “appropriate public and private entities,” that the answer to the questions above is that “significantly different challenges are presented for patients when reference products are nonbiologic complex drug products that have not been fully characterized or when reference products are biological products that are within the scope of the exception under [BPCIA § 7002(e)(2)],” then that determination triggers a series additional considerations, including:

1. What degree of characterization of the proposed generic version and the reference product should be required in order to determine the safety and effectiveness of the generic version;
2. What degree of similarity should be required to deem that the active ingredient of the proposed generic version is the same as the active ingredient of the reference product;
3. What types of evidence should be required to demonstrate that the proposed generic version is bioequivalent to the reference product;
4. What requirements should be established with respect to the comparability of the manufacturing process for the proposed generic version and the manufacturing process for the reference product;
5. Whether and to what extent clinical evidence is needed to demonstrate that there is no difference in immunogenicity between the proposed generic version and the reference product; and 
6. Whether and to what extent other clinical evidence is needed to demonstrate that the proposed generic version is as safe and effective for patients as the reference product.

Ultimately, consideration of these questions is intended to address whether FDC Act § 505(j) (concerning ANDAs) needs to be amended “to establish provisions that expressly address the approval of copy versions of nonbiologic complex drug products that have not been fully characterized, provisions that expressly address the approval of copy versions of biological products that are within the scope of the exception under [BPCIA § 7002(e)(2)], or both,” whether other changes to the law (i.e., FDC § 505(b)(2) and PHS Act § 351) need to be made, and whether FDA should develop a policy document “providing a comprehensive statement of general principles on the evidence that is necessary to obtain the approval of such Administration for proposed generic versions of reference products that are nonbiologic complex drug products that have not been fully characterized or that are biological products.”  The GAO report addressing each of these issues would be due not later than two years after the enactment of the “Generic Complex Drugs Safety and Effectiveness for Patients Act of 2015.”

With or without the passage of H.R. 1576, we’re likely to see some interesting questions and controversies crop of with the BPCIA’s transition provisions.  For instance, what happens if FDA approves an A-rated generic version of a biological product that come March 2020 will be deemed a license under the PHS Act?  Does that A-rating transition into an interchangeable biological product or not given the statutory requirements for interchangeability?  And what about the applicability of pediatric exclusivity to patents currently listed in the Orange Book for biological products that will be deemed licensed under the PHS Act?  Does that exclusivity simply disappear given the BPCIA's pediatric exclusivity limitation and lack of a patent listing mechanism?  Also, how will FDA treat any ANDAs or 505(b)(2) applications pending review on March 23, 2020?