What are people recommending that FDA do, to improve the current balance between drug innovation and access to generic drugs?  The docket isn’t closed yet, but I’ve read the first 67 comments. . . .

Background

FDA held a public meeting in July to consider the Hatch-Waxman Amendments, asking for comment concerning its administration of the amendments “to help ensure the intended balance between encouraging innovation in drug development and accelerating the availability to the public of lower cost alternatives to innovator drugs is maintained.”  It also opened a docket for written comments, which was originally slated to close on September 18.  On September 19, it extended the date for submission of comments to November 17.   What follows is a high level overview of some of the main recommendations for FDA in the first 67 comments.

Some comments speak broadly about perceived successes or failures of the Hatch-Waxman Amendments, or about preferred policy goals within the Hatch-Waxman framework.  Many recommend federal legislation or actions to be taken by other government agencies, like CMS and the FTC.

I am mainly interested here in the concrete recommendations for FDA, some of which have nothing to do with the Hatch-Waxman Amendments per se.  Some of these would (in my view) require legislative change, but the commenters seem to think otherwise, and so I have left them on the list.  The recommendations that clearly require legislative changes have not been included.

Here are some recommendations, sorted by topic. I’ll cover additional issues (including REMS, citizen petitions, reverse payment settlements, and “product hopping”) in another post.

General Recommendations

Commenters stated that FDA should

• work with the FTC more closely to address anticompetitive behavior
• work with its sister agencies in the Public Health Service to assess whether and what changes are needed to the Hatch-Waxman framework
• prepare an annual report on competitive conditions in the pharmaceutical sector (for instance, providing approval times for biosimilars and generics)
• require that each patient advocacy group participating at FDA disclose the people and entities that have financially or otherwise contributed to the group

New Drug Approval

Endpoints — Commenters stated that FDA should

• encourage new drug sponsors to use clinically meaningful outcomes rather than looking for small benefits that are statistically significant but not meaningful to patients

Orange Book listings — Commenters stated that FDA should

• require an NDA holder to identify the specific claims within a listed patent that would be infringed by ANDA applicants
• require NDA holders to promptly disclose upon initial approval all patents covering the approved drug that a generic might infringe or violate in developing a generic
• require NDA applicants/holders to provide an opinion letter from a patent attorney supporting the listing of each patent in the Orange Book for a particular drug

[The second and third may require legislative change, but the comments seem to assume otherwise, so I left them on my list.]

Inspections

Commenters stated that FDA should

• more rapidly communicate the compliance status of manufacturing facilities after inspections
• provide more feedback about steps that could be taken to make improvements responsive to inspection findings
• review corrective actions more rapidly, especially so that plants and lines making generic injectable drugs are not shut down for CGMP improvements

Generic Drug Approval

General — Commenters stated that FDA should

• resist calls to change safety or quality standards to speed access to generic drugs

Hiring — Commenters stated that FDA should

• accelerate hiring of staff using carryover user fee funds, to handle the rapid growth in meetings about and review of generic drug applications

Transparency — Commenters stated that FDA should

• respond to questions and requests from generic drug applicants about their pending generic drug applications
• create more guidelines and certainty for generic applicants seeking to market combination products
• when issuing new or updated guidance regarding active ingredient specific bioequivalence requirements that affect ANDAs under review (or for which the sponsor has already met with FDA), promptly communicate to each ANDA sponsor whether it will need to conduct additional testing (or modify its design) under the conditions set forth in the new guidance (or in the alternative, address this issue explicitly in the guidance)
• provide more transparency and timeliness as to regulatory exclusivity determinations (specifically, list exclusivity for innovative drugs at the same time as approval of those drugs)
• provide more information about the status of 180-day exclusivity, including the number of applicants that are first filers for a particular application and whether a first applicant’s exclusivity has been forfeit
• make the filing dates for ANDAs public
• make prior editions of the Orange Book readily available, and make it clear when information has been updated or changed
• release the Orange Book and other already public data in usable form (spreadsheet) so that academics, policy analysts, and other government agencies can measure agency outcomes

Review of applications — Commenters stated that FDA should

• eliminate the backlog of generic drug applications pending at the agency
• prioritize multiple generic drugs for each reference product
• prioritize review of ANDAs for off-patent off-exclusivity drugs that do not currently have an approved ANDA
• fast track review of ANDAs for generic injectable drugs
• develop a reputation for quickly approving high quality ANDAs
• implement a more specific timeline for expedited review of ANDAs for which there are three or fewer approved alternatives
• identify any FDA review practices that would foster faster approval of second and third (or more) generics for a particular reference product, including waiving fees, instituting priority or expedited review, and giving public notice when there are only one or two approved generic drugs (or off patent drugs) for the same indication on the market
• commit sufficient resources to support prompt review and approval of ANDAs, and to ensure early and active engagement with manufacturers to improve the quality of their applications and the speed and efficiency of the review
• treat lack of competition and high prices as creating an “unmet medical need” for purposes of programs that expedite review of applications.

Supplements — Commenters stated that FDA should

• expedite review of supplemental applications relating to manufacturing requests (to improve, modernize, or expand manufacturing)

Non-biological complex drugs — Commenters stated that FDA should

• Establish an external independent advisory committee to develop a consensus on the critical quality attributes for non-biological complex drugs, to determine whether these are sufficient to demonstrate pharmaceutical equivalence of these drugs, and to determine whether/what clinical trials are needed to establish therapeutic equivalence
• Approve copies of non-biological complex drugs only through the 505(b)(2) pathway rather than through the ANDA pathway.

Biosimilars

Guidance for applicants; review of applications — Commenters stated that FDA should

• put more emphasis and agency resources into approving the existing queue of biosimilar applications
• accelerate hiring of staff using carryover user fee funds, to handle the rapid growth in meetings about and applications for biosimilar biologics
• Commit sufficient resources to rapidly finalize FDA guidance (for instance on labeling, interchangeability, nonproprietary names, and transition products) and to support prompt review and approval
• identify any FDA review practices that would foster faster approval of second and third (or more) biosimilars for an innovative biologic, including waiving fees, instituting priority or expedited review, and giving public notice when there are only one or two approved biosimilars for the same indication on the market

Standards for licensure — Commenters stated that FDA should

• carefully reject innovative industry initiatives to mandate reliance on historical scientific methods, and instead adopt a flexible approach that allows biosimilar companies to introduce innovative science to prove biosimilarity.

Naming — Commenters stated that FDA should

• change its approach to nonproprietary names; that is, ensure that a reference product and all follow-on products share the same nonproprietary name
• eliminate the four-digit suffix for biosimilar names
• instead, implement the new proper name policy for all biologics, so that all biologics (including innovative biologics) have four letter suffixes

Interchangeability — Commenters stated that FDA should

• quickly establish an interchangeable biologics standard and prioritize approval of interchangeable biologics
• use the phrase “therapeutic equivalence” for biologics found interchangeable, because the statute under which CMS acts uses the phrase.
• adopt a policy that statute substitution laws must not conflict with the substitution of biologics deemed interchangeable under the BPCIA (i.e., adopt a formal policy that biosimilar companies can cite when asserting preemption claims)
• ensure that substitutable biosimilars have identical nonproprietary names to their corresponding reference products.

Transparency — Commenters stated that FDA should

• require innovators to promptly disclose upon initial approval all patents covering the approved biologic that a biosimilar company might infringe or violate in developing a biosimilar
• improve the Purple Book so that it is easier to access and search, and also increase the amount of information provided.

MORE TO FOLLOW . . .

** Disclosure: I filed comments of my own (a copy of my testimony in the U.S. House in July 2017).  I had testified on my own behalf, and I filed the comments on my own behalf.  Nevertheless, readers probably should know that I filed comments.