Lentis/Pharma’s influence in FDA

Introduction The FDA and Big Pharma: A Relationship Built on Influence The Food and Drug Administration (FDA), is the sole agency tasked with overseeing the pharmaceutical industry, however the pharmaceutical industry has a profound influence on the FDA through lobbying and user fees. In 2022, user fees, which is a fee charged to pharmaceutical companies when they submit a new application for FDA consideration, accounted for $2.9 billion, 47%, of the FDA’s $6.2 billion budget, in the year 2022Parasrampuria Sonal https://www.ncbi.nlm.nih.gov/books/NBK603243/ FDA User Fees: Examining Changes in Medical Product Development and Economic Benefits: Issue Brief Beleche Trinidad 2023 Office of the Assistant Secretary for Planning and Evaluation (ASPE) HHS ASPE Reports Washington (DC) 38691032. These fees are a double edged sword, they raise questions about the FDA’s accountability while helping fund new potential breakthroughs. Additionally, the pharmaceutical industry heavily lobbies the FDA, spending over $383 million in 2023 alone on lobbyingPharmaceuticals/Health Products Lobbying Profile https://www.opensecrets.org/federal-lobbying/industries/summary?cycle=2023&id=H04 2024-12-10 OpenSecrets en. There are many participants in this power struggle, from pharmaceutical giants like Pfizer and Eli Lilly, the Food and Drug Administration, the Insurance companies such as United Healthcare, Community Advocacies such as Public Citizen, trade associations such as Pharmaceutical Research and Manufacturers of America (PhRMA), and finally the consumers of the drugs. To limit the scope of this chapter, we will focus primarily focus on the history of pharma in the United States. The Evolution of the Pharmaceutical Industry The modern pharmaceutical industry can trace its roots back to a company known as Merck, which industrialized the production of pharmaceuticals in 1827Rang, H. P., & Ritter, J. M. (2012). The development of the pharmaceutical industry. In Drug discovery and development: E-book (3rd ed.). Elsevier.. From there, the pharmaceutical industry experienced several years of intense growth, primarily coinciding with large wars. The first large growth period was during the Civil War when there was intense demand for drugs such as Morphine, which was a painkiller, and chloroform, which was used as an anesthetic during surgeries. This led to the growth of Pfizer and Squibb, which today is known as Bristol Myers Squibb. Following this, there was another intense period of innovation in the pharmaceutical industry from 1918-1928, during which Penicillin, the first antibiotic, and Insulin were discovered and later industrially produced by pharmaceutical companies. Following World War 2, the pharmaceutical industry began widely commercializing antibiotics such as Penicillin, which led the industry to begin to reap large profitsSwann, J. P. (1995). The Evolution of the American Pharmaceutical Industry. Pharmacy in History, 37(2), 76–86. Jstor.. This created an anti-pharma sentiment in the United States, illustrated by this statement by George Merck, member of the Merck family who initially industrialized pharmaceutical production in 1827, “Medicine is for the people. It is not for the profits” 1891 History https://www.merck.com/company-overview/history/ 2024-12-10 Merck.com en-US. This conflict over the pharmaceutical industry's profits was only worsened in 1977 when Tagamet became the industry's first “blockbuster drug”, meaning that it earned over $1 billion dollars annuallyLi Jie Jack https://academic.oup.com/book/40666 Blockbuster Drugs 2014-01-23 Oxford University Press 978-0-19-973768-0 en 10.1093/oso/9780199737680.001.0001. This ignited an arms race of sorts between the pharmaceutical companies to develop the next blockbuster drug. This development is seen as the birth of the modern pharmaceutical industry. The Origins and Role of the FDA Now examining the history of the FDA, it was initially founded in 1906 as the Bureau of Chemistry with the signing of the Pure Food and Drug Act and became the Food and Drug Administration in 1930. The FDA did not take on the role of ensuring drug safety until 1938, following the Elixir Sulfanilamide disaster which was an incident where over 100 died due to an unsafe drug2006 A History of the FDA and Drug Regulation in the United States https://www.fda.gov/media/73549/download live U.S. Food & Drug Administration. In 1958, the Thalidomide scandal occurred in Europe, which was a drug that was marketed to expecting mothers as a cure for morning sickness, but resulted in horrible birth defects. Luckily, the FDA refused to approve the drug for use in the United States thanks to a woman named Dr. Frances Kelsey who recognized that there wasn't enough testing of the drug completed to warrant an approvalHow a courageous physician-scientist saved the U.S. from a birth-defects catastrophe - UChicago Medicine https://www.uchicagomedicine.org/forefront/biological--sciences-articles/courageous-physician-scientist-saved-the-us-from-a-birth-defects--catastrophe 2024-12-10 www.uchicagomedicine.org en. This scandal made the FDA viewed as the global protector of public health and most importantly the need for rigorous drug testing and evaluation. This scandal shaped the modern interaction between the FDA and big pharma companies. Voices of Influence The Industry Powerhouses Pro-Big Pharma groups like PhRMA hold significant influence over the FDA’s regulatory process. PhRMA's continued support for reauthorization of the Prescription Drug User Fee Act (PDUFA) highlights its commitment to Pharmaceutical Companies directly funding the FDAMitchell Aaron P. Trivedi Niti U. Bach Peter B. 2022-04-01 The Prescription Drug User Fee Act: Much More Than User Fees https://pmc.ncbi.nlm.nih.gov/articles/PMC8917050/ Medical care en 60 4 287 10.1097/MLR.0000000000001692 PMC8917050 35149663. In 2023, PhRMA spent 27.6 million dollars lobbying Congress to maintain market exclusivity and oppose federal price controls for pharmaceutical companiesPharmaceutical Research & Manufacturers of America Lobbying Profile https://www.opensecrets.org/federal-lobbying/clients/summary?cycle=2023&id=D000000504 2024-12-10 OpenSecrets en. Similar groups, such as the National Pharmaceutical Council (NPC) justify the high drug prices associated with the PDUFA, claiming they are essential for funding research and development in the pharmaceutical sector. The NPC has published “robust empirical evidence” claiming that “reducing market size or expected economic returns, or the potential for reduction in these returns, hurts innovative output”2022-07-26 The Impact of Price Regulation on Innovation: What the Research Shows National Pharmaceutical Council https://www.npcnow.org/resources/impact-price-regulation-innovation-what-research-shows 2024-12-10 www.npcnow.org en. The line between innovation and exploitation becomes blurred as large pharmaceutical manufacturers such as Eli Lilly and Novo Nordisk are backed by trade associations like PhRMA and NPC. As a result, consumers often bear the financial burden of innovation through increased drug costs. The Guardians of Public Health In contrast to pro-industry advocacies, groups like Public Citizen and Patients for Affordable Drugs (P4AD) actively defend public well-being. Although the PDUFA was passed to help fund operations and review processes for prescription drugs, Public Citizen believes “the introduction of drug and medical-device user fees gradually resulted in a fundamentally dangerous shift in the relationship between the FDA and the regulated pharmaceutical and medical-device industries, such that the agency now views these companies as partners and customers rather than regulated entities”2022-12-01 Outrage of the Month: Congress Reauthorizes FDA-Corrupting User Fees for Five More Years https://www.citizen.org/article/outrage-of-the-month-congress-reauthorizes-fda-corrupting-user-fees-for-five-more-years/ 2024-12-10 Public Citizen en. Thus, the drug approval process becomes less transparent and more dependent on a “you scratch my back and I’ll scratch yours” model between Big Pharma and the FDA. While out of pocket costs for drugs increase among consumers, large pharmaceutical companies continue to spend more on stock buybacks and dividends than research and developmentUS v Pharma - Fighting to Protect Medicare Negotiation https://www.fightpharma.org/ 2024-12-10 US v Pharma en. Additionally, expedited drug approval processes raises concerns on the prioritization of speed over safety. These expedited approvals often rely on weaker evidence compared to traditional measures, raising safety concerns, particularly for medicines and therapies targeting rare, life-threatening diseases2018-01-01 FDA Lax in Evaluating Drugs Approved Through Expedited Pathways, Studies Show https://www.citizen.org/news/fda-lax-in-evaluating-drugs-approved-through-expedited-pathways-studies-show/ 2024-12-10 Public Citizen en. Bridging the Divide A final subset of advocacy groups straddle the line between industry and public health support. The National Organization for Rare Diseases (NORD) championed the Orphan Drug Act, which incentivizes pharmaceutical companies to develop treatments for rare diseases that have small markets. While the Act has led to medical breakthroughs for under-researched diseases, critics argue that it excludes subsets of affected populations, such as children2023-04-24 Congress should protect the intent of the Orphan Drug Act and pass the RARE Act - National Organization for Rare Disorders https://rarediseases.org/pass-the-rare-act/ 2024-12-10 rarediseases.org en-US. Similarly, the Alliance for Regenerative Medicine (ARM) works in conjunction with the FDA to promote innovative solutions in Regenerative Medicine Advanced Therapy. However, breakthroughs in technology present challenges in ensuring consistent manufacturing and reproducibility of medicines and therapeutic processes. The ARM promotes “minimal differences in manufacturing processes for drug substance and/or drug manufacturing, and purification, such that leveraging of data from one product to another is suitable”August 27, 2024 ARM's Comments on the FDA's Draft Guidance: 'Platform Technology Designation Program for Drug Development' https://alliancerm.org/wp-content/uploads/2024/10/FDA-2024-D-1829-0050_attachment_1.pdf live Alliance for Regenerative Medicine. This approach supports faster development but raises concerns about quality control and safety. Pharma and FDA Interaction User Fees User fees, formally introduced in through the Prescription Drug User Fee Act (PDUFA) of 1992, marked a turning point in the relationship between the FDA and pharmaceutical industry. This Act aimed to expedite the drug approval process by allowing pharmaceutical companies to pay fees when submitting drug applicationsResearch Center for Drug Evaluation and 2024-11-22 Prescription Drug User Fee Amendments https://www.fda.gov/industry/fda-user-fee-programs/prescription-drug-user-fee-amendments 2024-12-10 FDA en. This additional funding strengthened the FDAs resources, enabling quicker reviews and fostering innovation for public health. Initially, this idea was practical, as the FDA required financial support to handle the increasing responsibility of evaluating drugs. This was heightened by public outcry and frustration during the AIDS epidemic in the United StatesBreen Tom 2021-05-21 Why is the FDA Funded in Part by the Companies It Regulates? https://today.uconn.edu/2021/05/why-is-the-fda-funded-in-part-by-the-companies-it-regulates-2/ 2024-12-10 UConn Today en-US. However, user fees have evolved from a financial boost to an integral part of the FDA’s budget. In 2022, user fees accounted for $2.9 billion of the FDA’s budget, this being 47% of all funding. This financial reliance raises concerns, including “a lack of FDA independence” and “medical safety issues” regarding FDA approved productsGabay Michael 2018-04-01 The Prescription Drug User Fee Act: Cause for Concern? https://journals.sagepub.com/doi/10.1177/0018578718757519 Hospital Pharmacy en 53 2 88–89 10.1177/0018578718757519 0018-5787 PMC5863890 29581600. Gabay states the pressure to meet PDUFA deadlines can lead to compromises in the thoroughness of drug evaluations, potentially exposing patients to risks. According to Carpenter and associates, incoming PDUFA deadlines often hastened decision making in the last few weeks of evaluation. Drugs approved in the last two months before deadlines were more often withdrawn for safety concerns, as well as more likely to carry black box warningsCarpenter Daniel Zucker Evan James Avorn Jerry 2008-03-27 Drug-Review Deadlines and Safety Problems https://www.nejm.org/doi/full/10.1056/NEJMsa0706341 New England Journal of Medicine 358 13 1354–1361 10.1056/NEJMsa0706341 0028-4793. Despite these concerns, the FDA pushes its statistics regarding innovation and efficiency, reporting 37 novel drug approvals in just 2022 2023 New Drug Therapy Approvals 2022 https://www.fda.gov/media/164429/download . Observing the data more closely, in fiscal year 1993, the drug application fee started at $100,000, with total revenue from fees reaching $36 million. By fiscal year 1997, these fees grew substantially, rising to $233,000 and total revenue reaching $84 millionPrescription Drug User Fees Act, H.R.6181 § 379g et seq. (1992).. When observing fiscal year 2025, the contrast is even larger. Fees for applications requiring clinical data reached $4.3 million, while fees without data reached $2 million. This drastic increase reflects inflation and the expanding scope of FDA operations, but more accurately demonstrates the growing reliance on user fees as a funding source. Buying Loyalty The financial ties between the FDA and the pharmaceutical industry lie not only in the general bodies but also in specific individuals. Investigations in physician disclosures reveal that many FDA advisors receive funding from pharmaceutical companies whose drugs they reviewHidden conflicts? Pharma payments to FDA advisers after drug approvals spark ethical concerns https://www.science.org/content/article/hidden-conflicts-pharma-payments-fda-advisers-after-drug-approvals-spark-ethical 2024-12-10 www.science.org en.  An analysis of 107 FDA advisors between 2008 and 2014 revealed that 66 advisors received varying payments after advising the approval of 28 drug products. Of these advisors, 6 received payments of over a million USD, another 20 receiving within the range of $100,000 to one million dollars. In the case of Brilinta, AstraZeneca, the drugs manufacturer, and its competitors paid slightly more than one million dollars to various FDA advisors after the vote. These payments, ranging from travel expenses to consulting fees, highlight a troubling pattern of influence from both drug applicant companies as well as their competitors. While such financial relationships may be legal, they raise serious ethical concerns about potential bias when advising FDA decisions. The presence of these under reported ties undermines the trust of these organizations and casts doubt on the validity of FDA voting procedures. References