House Appropriators Tip-Toe Into Biologics Transition Controversy
Executive Summary
US FDA instructed to use the "Program" when assessing insulin applications with review goals before the 2020 transition date, but appropriations report does not explicitly urge elimination of the application "dead zone."
US House appropriators addressed the so-called regulatory "dead zone" for insulin products about to switch from regulation as drugs to regulation as biologics, although not as forcefully as recently-proposed Senate legislation.
Language in the report accompanying the House fiscal year 2020 Agriculture, Rural Development and US Food and Drug Administration appropriations bill, which was marked up and sent to the floor 4 June, encourages the agency to use specific programs to assess insulin products with user fee goals prior to 23 March 2020, the statutory date they would move from drug to biologics regulation.
The committee said in the report that "to ensure patient access to lower-cost insulin," relevant insulin applications should be assessed using the PDUFA V "Program," the model implemented in 2012 for many NMEs that allows mid- and late-assessment cycle communications. The Program extended assessments by creating a two-month filling period before the review clock starts. (Also see "PDUFA V 'Program' First-Cycle Approval Rates Significantly Higher For All Applications" - Pink Sheet, 12 Dec, 2016.)
In addition, the agency was asked in the report to "work to identify and promote efficiencies in the review" of any insulin applications submitted under the Public Health Service Act that were previously submitted under the Food, Drug and Cosmetic Act with goals before 23 March 2020 and were not approved by that date.
The 2009 Biologics Price Competition and Innovation Act mandated that insulin, human growth hormone and some other protein products that are regulated as drugs to be regulated as biologics beginning on 23 March 2020.
Stakeholders and industry raised concerns when the agency said in guidance on the transition that some Food, Drug and Cosmetic Act Section 505 applications submitted for a biologic product subject to the transition that are not approved by 20 March 2020 would receive a complete response letter, forcing them to be re-submitted. (Also see "A Guide To US FDA’s Drug-To-Biologic Transition Process" - Pink Sheet, 8 May, 2019.)
As a result, sponsors are not expected to submit affected applications in the months leading up to the transition because they may be forced to start over as a BLA, creating what has been called an application "dead zone." (Also see "Insulin Applications Intended For Biosimilar Pathway May Already Be At US FDA" - Pink Sheet, 2 Apr, 2019.)
The House language does not attempt to eliminate the dead zone, but may be an attempt to provide some regulatory certainty to sponsors who have insulin applications awaiting an agency approval decision.
The report does not go as far as a recently released Senate drug pricing bill, which would eliminate the possibility that a CR could be issued in those cases. The Health, Education, Labor and Pensions Committee's discussion draft would require applications assessed under Food, Drug and Cosmetic Act Section 505 and filed by 23 September to continue to be reviewed, even if the review lasts beyond the transition date. Upon approval (or 23 March 2020, whichever is later), those applications would immediately be deemed BLAs under the Public Health Service Act. (Also see "Biologics Transition 'Dead Zone' Could Be Eliminated Under US Senate Bill" - Pink Sheet, 28 May, 2019.)
Committee members also urged the agency in the report to "act quickly" in reviewing the feedback and recommendations received during the 13 May public meeting on the future of insulin biosimilars. Among the ideas offered was allowing follow-on insulins to use the interchangeability pathway without first being approved as a biosimilar. (Also see "Best Pathway To Interchangeable Insulins Is In The Eye Of The Beholder" - Pink Sheet, 15 May, 2019.)
Language On Genetic Modification Of Embryos Re-Inserted
During the mark-up, committee members decided to include a ban of funding for FDA to receive applications involving intentional heritable genetic modification of an embryo, approving the amendment by voice vote.
The provision had been in FDA appropriations bills the last four years, but was left out in the initial version of the FY 2020 bill. (Also see "US FDA Wins Big In Shutdown-Averting Approps Bill" - Pink Sheet, 14 Feb, 2019.)
Members indicated that there are moral and ethical questions involving such gene editing, but some also worried about a blanket denial of the practice, which could prevent mitochondrial replacement therapy from moving forward.
Several committee members agreed that the ban should be reviewed going forward, in part because many of those questions may be resolved.
Rep. Andy Harris, R-MD, who is a physician, said he supported the amendment "with the caveat that this is going to need to be looked at because the technology is advancing way more rapidly than what this amendment suggests."
Bill, If Enacted, Would Boost FDA Funding
The FDA would receive $5.85bn in the House bill, a 4.7% increase compared to the FY 2019 funding bill, but significantly less than President Trump allocated in his budget request.
The Center for Drug Evaluation and Research would receive the largest increase within the agency, $98.7m. (Also see "US FDA Gets Another Appropriations Increase In FY 2020 House Bill" - Pink Sheet, 22 May, 2019.)
While the funding level is another win for the FDA, it was not based on budget numbers that have been agreed to by the Senate and White House, a complaint Republicans made during the mark-up. Until an agreement is reached, enactment likely remains in doubt.
The Senate has not yet released its FY 2020 FDA appropriations bill.