Continuous Pharmaceutical Manufacturing Bill Hitches A Ride With US FDA User Fee Legislation
Executive Summary
US legislation could advance new manufacturing platforms for drugs and biologics with academic R&D and workforce development and in turn spur domestic growth.
Legislation promoting the research and development of advanced and continuous pharmaceutical manufacturing technologies has again won US House approval, this time as part of must-pass FDA user fee legislation, which should increase its chances of finally winning Senate approval and becoming law.
The advanced and continuous manufacturing provision is missing from the version of the legislation to renew user fees for another five years that the Senate is considering, but could wind up in the final bill depending on how the chambers reconcile differences.
The US Food and Drug Administration has led the charge in recent years for the US government and US-based pharmaceutical manufacturers to invest in continuous manufacturing alternatives to traditional batch processing as a way of increasing drug quality as well as boosting the financial viability of domestic pharmaceutical manufacturing.
Increasingly, however, the focus is turning to an array of new manufacturing technologies including additive manufacturing and a variety of gene and cell therapy manufacturing technologies. The legislation could help fill gaps in establishing new manufacturing technology platforms for a variety of therapeutics, some of them curative, that are being explored in academia.
The House last passed a standalone version of the National Centers of Excellence in Advanced and Continuous Pharmaceutical Manufacturing bill, H.R. 4369, in October 2021, on a broadly bipartisan basis, with 217 Democrats and 151 Republicans in favor, 56 Republicans against and seven members not voting.
Senate records show the organizations lobbying Congress on that bill were the American Society of Anesthesiologists, GlaxoSmithKline Inc., Pharmaceutical Research and Manufacturers of America, Rutgers University, the University of Connecticut, the University of Kansas and the Association of American Universities.
Rep. Frank Pallone, D-NJ, who chairs the House Energy and Commerce Committee, sponsored that bill, with Rep. Brett Guthrie, R-KY, as the lone co-sponsor.
Pallone and Guthrie had likewise sponsored a version they introduced during the previous congressional session in October 2019. That bill failed to make it into the CARES Act, while finding a place in the follow-on HEROES Act that the House passed but the Senate never considered. (Also see "Continuous Manufacturing Back In Second Act" - Pink Sheet, 13 May, 2020.) (Also see "Continuous Manufacturing Centers Of Excellence Measure Resurfaces In US House" - Pink Sheet, 22 Sep, 2020.)
A Late Addition On The Way To House Floor
The Energy and Commerce Committee reported out a user fee bill, H.R. 7667, on 18 May, that did not mention the centers of excellence. Pallone later inserted the centers of excellence bill as a new section 706 of the House user fee bill before forwarding it the House Rules Committee for the 7 June House floor vote, although only after checking with the committee’s minority leadership, a spokesman said.
Pallone’s centers of excellence bill is only the latest to ornament the “Christmas tree” user fee bill, which could attract more such decorations as the House and Senate work out differences between their user fee bills. (Also see "Decorating The 'Christmas Tree’: US House Bills That Could Be Tacked Onto FDA User Fee Legislation" - Pink Sheet, 1 Apr, 2022.)
The Senate Health, Education, Labor and Pensions Committee has scheduled a 14 June markup on the Senate user fee bill, S. 4348, the FDA Safety and Landmark Advancements Act of 2022, introduced 27 May by committee chair Patty Murray, D-WA, and ranking member Richard Burr, R-NC. (Also see "Therapeutic Equivalence Evaluations Would Be Required For 505(b)(2) Drugs Under Senate User Fee Bill" - Pink Sheet, 30 May, 2022.)
The Senate user fee bill is missing all but one element of an inspections subsection of the House bill, a provision for better internal FDA coordination to prevent drug shortages that originated in identical House and Senate versions of the Manufacturing API, Drugs and Excipients (MADE) in America Act, H.R. 3927 and S. 2082. (Also see "House User Fee Bill’s Inspections Provisions Would Add Layers Of Scrutiny Abroad" - Pink Sheet, 6 May, 2022.)
A Potentially $100m/Year Infusion Of Research Funding
The legislation authorizes $100m/year for fiscal years 2023-2027 for as many as five centers of excellence formed by universities or university consortia.
It gives the FDA one year after enactment to solicit and receive requests for designation as national centers of excellence.
It spells out criteria for granting the designation. For example, the institutions or consortia must show they have the requisite physical and technical capacity, knowledge-sharing networks, ability to development and transfer technologies, and partnership experience – including the ability to support pharmaceutical companies, federal agencies and the US workforce.
Several universities have been developing such capabilities, most notably the Massachusetts Institute of Technology in Cambridge, MA, and Rutgers University, which has campuses in New Brunswick, Newark and Camden, NJ.
The bill gives the agency authority to terminate centers of excellence that no longer qualify with 90 days’ notice. To qualify, they must agree to collaborate with the FDA on reports, share data with the agency on best practices, to work with industry and other excellence centers on roadmaps for workforce development and for strengthening relationships among centers of excellence, and to report to the FDA annually on their activities.
The funding, which the government can award through grants, contracts or cooperative agreements, can focus on expanding related research and development capacity, particularly for accelerating development of drug products in response to emerging medical threats like drug shortages, quality-related supply chain disruptions, epidemics and pandemics.
Within two years of designating its first center of excellence, the Department of Health and Human Services must report to Congress on a long-term vision of the FDA’s role in supporting advanced and continuous pharmaceutical manufacturing.
The report should show that there is a framework of principles for the initiative, plans for developing relevant regulations and guidance on the development of advanced and continuous manufacturing technologies and on how the FDA should review them, and plans for seeking public feedback.
A Congressional Budget Office analysis based on the previous identical standalone version of the bill estimated that, based on historical spending for similar activities, even if Congress appropriates the full $100m/year, the government will probably only spend $72m/year during the five-year funding period, with the rest spent afterward.