Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

Jill Wechsler

US Capital Building. | Image Credit: © W.Scott McGill - © W.Scott McGill - stock.adobe.com

In the 30 years that I have been writing about FDA policy and biopharmaceutical research and drug manufacturing, I have not encountered a time as troubling or uncertain as the present. The political battles over medications for abortion, vaccine safety, and shortages in vital medicines undermine long-held confidence and support for the nation’s regulatory system for food, drugs, and medical products. Add to that Congressional delays in reauthorizing national initiatives to prepare for future pandemics, incentives to develop much needed anti-infective medicines, and funding for the highly acclaimed PEPFAR (the US President’s Emergency Plan for AIDS Relief) program, which provides antiviral medicines to combat AIDS around the world.

 Washington reporter, Jill Wechsler, is ending her tenure as a contributing editor to the publication. In January of 1990, Jill’s column, titled “New Era for the Pharmaceutical Industry”, highlighted attacks on the US drug regulatory process that called for stricter regulations. Ironically, if you read Jill’s final column in this issue of PharmTech, it seems that as much as the industry has changed and evolved, some things remain the same.

Jill’s reporting on decades of regulatory and government topics has given her a unique perspective on the pharmaceutical industry that cannot be reproduced, and we here at PharmTech will greatly miss her. We thank Jill for her journalistic integrity, hours of coverage at conferences, countless blog posts, and numerous articles.

We wish her all the best for her future endeavors!

To read Jill’s extensive coverage of FDA and other regulatory news, Jill’s Regulatory Watch column can be accessed on our website at 

Jill covered a variety of topics in her PharmTech Talk blog posts over the years. To read past PharmTech Talk posts, visit 

Jill may be contacted at jillwechsler7@gmail.com. 

Congressional infighting over federal spending furthermore threatens to limit funding and support for FDA as well as the National Institutes of Health (NIH) and vital national health programs. Such developments undermine the nation’s leadership in biomedical research and discovery of cutting-edge medical treatments. The situation could get worse, moreover, if the Supreme Court permits states to limit access to medical products approved as safe and effective by FDA, but with medical uses opposed by certain interest groups.

These and other contentious issues seem to ignore the remarkable success over the past three years of the public-private partnership that linked government funding to industry research to produce treatments able to arrest the spread of COVID-19. And even though FDA policies have long provided the “gold standard” around the world for conducting clinical research to assess the safety and efficacy of untried
therapies, the political attacks on the United States regulatory process are exhausting its leaders and undermining agency morale.

As Washington correspondent for Pharmaceutical Technology®, I have commented extensively on these and a wide range of political, legal, and regulatory developments that have shaped medical product R&D and production in the US and abroad. I became familiar with drug regulation soon after Congress enacted legislation creating the modern generic drug industry and as FDA revised clinical research and regulatory policies in response to the AIDS epidemic. And while it was clear in 2004 that a Medicare drug benefit would greatly expand access to medicines for elderly Americans, it also set the stage for increased government scrutiny of prescription drug prices, as demonstrated by recent events.

Similarly, the biotechnology revolution has opened the door to major advances in treatment of critical medical conditions, laying the groundwork for a whole new industry in the US and abroad. But the growing realization that many Americans struggle to afford those costly new medicines, as compared to citizens in other wealthy countries, has eroded public confidence in pharma and supported calls for patent and pricing reform. Manufacturers now are accepting Medicare price negotiations to avoid being shut out of program coverage, but participation may erode if such policies dry up private investment in the discovery of vital new therapies for patients, as industry predicts.

Although drug shortages will continue to draw more fire on the political front due to antiquated and often unreliable production processes, a main problem is that many of the products now in limited supply are low-cost generic drugs made by companies with limited resources to fund modern manufacturing operations. Innovation in this area may finally gain ground, though, as a way to expand availability of new gene and biotech therapies that are costly to produce and distribute.

The COVID-19 national emergency exposed the fragility of our public health system and public confusion about programs and policies needed for a thriving biomedical research enterprise equipped to further tackle cancer, dementia, and a host of debilitating conditions. I can only hope that policy makers will look for ways to encourage, and not derail, such efforts, and that the nation will support policies and programs that improve the health and well-being of society—and avoids imposing personal beliefs on others that can limit access to life-saving and life-enhancing treatments.

Jill Wechsler is Washington reporter for 

When referring to this article, please cite it as Wechsler, J. Signing Off from Washington. 

Articles

FDA and industry face unprecedented political and policy challenges.

Signing Off from Washington 

As part of agency initiatives to strengthen its oversight of human food and food products, FDA is revising inspection and compliance programs for all regulated products, at home and abroad. While an overriding aim is to improve FDA’s capability for monitoring and curbing contamination issues involving foods, the changes also involve revised oversight and inspection programs for medicines and other regulated products. Some of these actions arise from FDA’s greater reliance on remote oversight activities advanced during the global COVID pandemic, which encouraged more cooperation with foreign inspection programs. Others have been advanced by FDA for years, such as encouraging modern manufacturing processes and attention to quality issues to ensure reliable supplies to prevent drug shortages.

For these purposes, FDA is in the process of restructuring its Office of Regulatory Affairs (ORA) to better monitor food safety issues and to schedule field inspections more efficiently. A prime aim is to prevent delayed responses to serious food contamination issues, as occurred with the baby-formula recall in 2022, which created a national crisis in formula shortages (1). FDA Commissioner Robert Califf announced in June 2023 a revised model for ORA to better align with a new unified Human Foods Program and to coordinate and respond expeditiously to public health issues (2). Califf further implemented these changes with the appointment of the first Deputy Commissioner for Human Foods on August 23, 2023 (3). This high-level official will oversee all human foods programs and work closely with a new associate commissioner for regulatory affairs who will head up revamped ORA operations.

As part of these changes, FDA said in its June 2023 announcement that it will shift certain enforcement functions currently managed within ORA to compliance offices in FDA centers. This move aims to “streamline operations and expedite decision-making” so that the agency can determine more quickly what sites to inspect and what compliance actions to take. ORA will focus more on conducting investigations, inspections, and oversight of imports, still operating through offices for medical devices, human & animal drugs, biologics, and bioresearch monitoring inspections (BIMO). More details on the plan are emerging and will involve Congressional review and more formal rulemaking, as well as agreement from FDA unions and staff.

Furthermore, ORA is taking steps to strengthen its oversight of domestic and foreign drug manufacturing activities. Alonza Cruse, director of ORA’s Office of Pharmaceutical Quality Program Operations, reported at the PDA/FDA joint regulatory conference in September 2023 that the agency has resumed foreign inspections,
including those in China, and is implementing pilot programs for unannounced inspections of manufacturing facilities in China and India. Cruse also noted an expansion in cooperative inspection activities with European and other regulatory authorities under enhanced mutual recognition agreements (MRAs).

These initiatives reflect recent Congressional directives. Under the Food and Drug Omnibus Reform Act (FDORA) enacted in late 2022, the legislators encouraged more unannounced FDA inspections of foreign drug establishments, shifting away from FDA’s usual practice of scheduling foreign site visits in advance to ensure access to the facility. At the same time, FDORA aimed to reduce unneeded foreign site visits by supporting expanded FDA use of MRAs with trusted foreign regulatory counterparts to obtain reports and information related to pre-approval inspections, as well as more routine manufacturing site visits. The legislation supports FDA recognition of inspections by foreign regulatory counterparts, such as the European Union, the United Kingdom, Switzerland, and other established agencies, in an ongoing effort to minimize duplicative site visits by all parties.

Similarly, the Center for Drug Evaluation and Research (CDER) is ramping up its compliance and inspection efforts to further encourage quality production operations and prevent drug shortages. CDER director Patrizia Cavazzoni emphasized at the PDA/FDA conference the importance of manufacturers maintaining proactive and prevention-focused quality systems to ensure “sustainable compliance” with current good manufacturing practice (CGMP). This involves ongoing oversight of facilities by senior management, effective systems for detecting emerging quality issues, and a structured approach to determine the root cause of such problems.

A prime objective of such efforts is to prevent and mitigate shortages in critical drugs. While economic issues underly production shortfalls for many medicines, Cavazzoni cited drug quality problems and manufacturing delays as responsible for nearly half of new shortages last year. Increased authority for FDA to require early notification can help reduce the severe impact of certain supply situations, but CDER seeks proactive and prevention-focused quality systems at facilities to ensure consistent compliance with manufacturing standards. This entails involvement of senior management to ensure adequate ongoing control and sufficient resources for the operation. Management should implement effective systems for detecting emerging issues and assess the root cause of any violations. Inspection reports and warning letters should be addressed with effective corrective actions procedures. A commitment to quality assurance by industry, Cavazzoni emphasized, is “essential for dependable drug supply.”

FDA’s emphasis on considering risk factors in planning for medical
product oversight also applies to BIMO investigations, an effort also encouraged by a provision in FDORA that clarifies FDA’s authority to conduct BIMO inspections and which sites and facilities are subject to this oversight and required to provide records and other information. FDA issued a guidance in April 2023 that makes recommendations to industry on implementing a risk-based approach to monitor investigational studies on human drugs, biologics, medical devices and combination products (4).

This expands on a 2013 guidance on this subject, here providing additional recommendations for sponsors in planning and developing research monitoring plans and assessing results from such activities. The guidance emphasizes the importance of data integrity in clinical trial monitoring and the need to design research protocols that identify potential risks for data collections. Centralized monitoring, moreover, should be applied across multiple clinical sites so that sponsors may detect inconsistencies or omissions in data and determine which clinical sites need further review.

FDA. FDA Provides Update on Proposed Human Foods Program and Office of Regulatory Affairs Restructuring. Press Release. Feb. 28, 2023.

FDA. FDA Provides Update on Proposal for Unified Human Foods Program, including New Model for the Office of Regulatory Affairs. Press Release. June 27, 2023.

FDA. FDA Names First Deputy Commissioner for Proposed, Unified Human Foods Program. Press Release. Aug. 23, 2023.

A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers, Guidance for Industry

The agency will be reorganizing field force and compliance functions.

FDA Inspections Face Overhaul

As the federal government began to roll out the rules and procedures for negotiating prices of drugs reimbursed by Medicare Part D plans, biopharma companies launched an attack on the legality of the controversial program. Merck took the lead in filing a detailed lawsuit on June 6, 2023 in the Washington, D.C. federal district court, claiming that the negotiation process established by the Inflation Reduction Act (IRA) violates the constitutional rights of manufacturers (1).

Merck and Bristol Myers Squibb (BMS), which filed a similar lawsuit a few days later in New Jersey, charged that the Medicare price setting program would involve a “taking” of private property for public use without just compensation, in violation of the Fifth Amendment to the US Constitution (2). In addition, these companies claimed that the IRA also is unconstitutional under the First Amendment right to free speech because the process would coerce a manufacturer to sign an agreement it opposes: any company that wants to walk away from a price negotiation deal it doesn’t agree with would have to pay an onerous fine for doing so and thus is denied free speech. Both manufacturers have much to lose under the new pricing program, as lead targets for the scheme include Merck’s Januvia and Keytruda and BMS’ Eliquis and Opdivo, which would undermine company efforts to test and reformulate these therapies for new life-saving and profitable uses.

Similar to the Merck and BMS suits and to subsequent filings by Johnson & Johnson and Astellas Pharma, the US Chamber of Commerce filed a complaint in Ohio also charging that the price negotiation program violates the manufacturers’ constitutional rights. It additionally claims that Congress lacks the power to levy the specified excise tax for noncompliance because that would “compel” commerce (3).

Next up, on June 21, 2023, the Pharmaceutical Research and Manufacturers of America (PhRMA) joined a lawsuit filed by National Infusion Center Association (NICA) and the Global Colon Cancer Association (GCCA) challenging the constitutionality of the price negotiation provisions in the IRA (4). The plaintiffs take issue with the IRA’s excise tax—the provision that sets an 18% fine or more on a drug’s annual revenues for refusing to comply with the negotiated rate. Such a penalty, they claim, is an “excessive fine” and violates the constitution because there is no provision for judicial review of the many decisions involved in determining negotiated prices under the program. The plaintiffs also argue that the new law breaches due process by denying public input on the how the program will be implemented.

Beyond the specific legal issues raised in these lawsuits, which ultimately may end up before the Supreme Court, biopharma companies continue to claim that the administration’s price negotiation scheme will discourage investment in more risky research and development programs for new cures, particularly for rare diseases. Although the program exempts orphan drugs from negotiations, manufacturers note that this applies only to the first approved indication, and not to additional uses of the therapy. That provision is expected to undermine manufacturers’ plans to test additional uses for therapies hit by negotiated prices, cutting off industry’s main strategy for discovering and developing new treatments for cancer and rare diseases.

The Centers for Medicare and Medicaid Services (CMS) meanwhile is working to implement the drug price negotiation program, as mapped out in a final guidance published June 30, 2023 (5). That document made some changes from its initial memorandum issued on March 15, 2023, responding partially to the industry lawsuits challenging CMS’ planned process for reaching agreement on negotiated prices by 2026 (6).

The documents outline what information CMS will require from manufacturers in order to select the first 10 drugs for negotiations by Sept. 1, 2023. The agency then will propose “maximum fair prices” in February 2024 and final prices by August 2024, which would become effective Jan. 1, 2026.The June advisory allows for more public discussion of the negotiation process and provides leeway for manufacturers to disclose proposed prices if they choose to do so.

The bottom line will be whether Medicare price negotiations actually reduce program outlays for drugs, as promised by the Biden administration alongside critics of high drug prices. Congressional approval of the program represented an unprecedented defeat for the pharmaceutical industry’s long-time efforts to block government price control initiatives. Pharma companies claim that they have long tried to facilitate patient access to needed medicines, but through individual discounts and other strategies that maintain market share. Industry also points to health insurers and pharmacy benefit managers for thwarting these efforts and limiting opportunities to reduce patient outlays for medicines. The legal challenges are only just beginning, and much can happen in Washington between now and 2026.

Wilson, M. R. Merck Sues HHS Over Drug Negotiation, Claims Program ‘tantamount to extortion’. 

BMS. Impact of the Inflation Reduction Act on Innovative Medicines for Patients. 

Stempel, J. US Chamber of Commerce Sues Over Government’s Drug Pricing Power. Reuters.com. June 9, 2023.

PhRMA, NICA, GCCA, PhRMA Litigation Asserts Price Setting
Provisions in the Inflation Reduction Act are Unconstitutional. Press
Release. June 21, 2023.

Medicare Drug Price Negotiation Program: Revised Guidance, Implementation of Sections 1191 – 1198 of the Social Security Act for Initial Price Applicability Year 2026

edicare Drug Price Negotiation Program: Initial Memorandum, Implementation of Sections 1191 – 1198 of the Social Security Act for Initial Price Applicability Year 2026, and Solicitation of Comments

When referring to this article, please cite it as Wechsler, J. Industry Challenges Medicare Price Negotiation Scheme. 

Manufacturer lawsuits prompt CMS to [slightly] modify pricing plan.

Industry Challenges Medicare Price Negotiation Scheme

The legislators departed Washington, D.C. in late July for a six-week summer recess without passing a host of critical budget bills, including key measures involving health care and drug regulation. At the top of the legislative to-do list are multiple appropriation bills to continue funding the federal government past Sept. 30, 2023. Another important measure on hold would reauthorize programs to prepare the nation for the next pandemic. And policies to rein in pharmacy benefit managers (PBMs) gained approval from some committees, but not a final vote.

Demands to radically cut spending and to further limit access to abortion erected major roadblocks to agreement on important funding bills, as conservatives in the House demanded spending cuts unacceptable to Democrats and moderate Republicans. Only the Department of Veterans Affairs saw its budget approved, enabling members of Congress to claim support for military veterans when engaging with constituents back home.

While the Senate passed most fiscal 2024 spending measures, very partisan proposal in the House blocked any agreement on final measures. Funding for the Department of Defense was stymied by Republican opposition to a Biden administration policy to fund travel of armed forces members to obtain abortion services. House Republicans alienated Democrats with cuts in multiple agencies in the Department of Health and Human Services (HHS), including the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) and proposed to eliminate the Agency for Healthcare Research and Quality (AHRQ), a perennial target of conservatives.

Similarly, the House measure to fund the Department of Agriculture, including FDA programs, made significant cuts in food program such as foreign food aid and support for US food exports, outraging both Republicans and Democrats from rural states. Not only was FDA’s overall budget slashed, but the bill sought to ban mail order delivery of the abortion pill mifepristone, a proposal that drew a veto threat from the Biden administration. The Agriculture/FDA funding bill in the Senate provides a slight 1% budget increase for FDA, which means less severe but still significant program reductions.

House and Senate committees made some progress on legislation to support national preparedness and response to future pandemics, which has to be reauthorized before it expires Sept. 30, 2023. But that tight timeframe for passing the Pandemic All Hazards and Preparedness Act (PAHPA) is encouraging lawmakers to include various pet programs and policies in the measure. The Senate Health, Education, Labor and Pensions (HELP) committee approved PAHPA on July 20, 2023, readying the measure for a vote by the full Senate in September. HELP committee chairman Bernie Sanders added a number of provisions, including one requiring drug manufacturers to notify FDA in advance of product shortages and other shortage-related provisions. While the legislators generally back continued support for preparedness, House Republicans moved to slash funding for the program, setting up a partisan battle over the program’s future.

Also pending is legislation to boost transparency and revise fees from insurers to pharmacy benefit managers (PBMs). These drug plan middlemen have been under attack from manufacturers and policy makers for failing to pass on savings to consumers and limiting patient access to certain medicines, and both the House and Senate held hearings this past year to consider reforms. Continued Federal Trade Commission investigation of PBM practices has set the stage for legislative reform.

Despite this support for change, the policy reforms in current bills appear relatively tame. The Senate Finance Committee recently approved a legislative package aimed at boosting transparency of PBM practices affecting Medicare Part D plans. And the House Ways & Means Committee similarly agreed to give patients and employers more information to stimulate competition in the field. House Republicans approved a bill that Democrats opposed as too weak, raising the likelihood of differing bills from the House and Senate in the fall which may be hard to reconcile.

With the August recess extending through mid-September, Congress will have only a few days to approve 12 appropriations bills and other expiring measures before the September 30 deadline. Unless the feuding parties reach some agreement, that could mean a federal government shutdown in October and added difficulties in maintaining the nation’s health care system, along with a viable drug approval and regulatory program.

Pandemic, PBM, and other policies on hold during the summer recess.

Congress Leaves Town with Major Drug-Related Bills on Hold

FDA recently granted full, or traditional, approval to Eisai Pharmaceutical’s Alzheimer’s treatment Leqembi, converting an earlier conditional approval status with further data from a multi-regional study of nearly 1800 patients. Results indicated that the drug slows the rate of cognitive and functional decline in early Alzheimer’s patients, compared to placebo, but also raised certain safety concerns. The 

for wider coverage of the drug by Medicare and establishes a process for further clinical testing and evaluation of treatments for this widespread, debilitating condition.

Eisai and partner Biogen had gained FDA accelerated approval for the drug in January 2023 based on evidence from a Phase II study. However, reimbursement was limited by the earlier decision of the Centers of Medicare and Medicaid Services (CMS) to pay for Alzheimer’s drugs only for those patients enrolled in clinical trials to further test the safety and efficacy of the therapy. This approach utilized CMS’ Coverage with Evidence Development (CED) policy, which limits access to certain innovative medical products while clinical trials continue and is most commonly used for new medical devices. It was very unusual and controversial for CMS to curb coverage for a drug granted accelerated approval by FDA and reflects concerns about potentially huge outlays for Medicare on a therapy that may have limited efficacy and potential adverse effects.

Now with the sponsor presenting trial data supporting full FDA approval, 

 it will provide appropriate, broader coverage for Leqembi. But reimbursement still will be contingent on physicians enrolling patients in registries so that CMS may track the effectiveness of the treatment and emergence of side effects going forward with broader patient use.

Eisai set the stage for FDA full approval by 

conducting a large Phase III placebo-controlled, double-blind, randomized study in North America, Europe, and Asia

. Study 301 Clarity AD enrolled 1795 patients with early Alzheimer’s disease, as seen in measures of mild cognitive impairment or mild dementia stage disease. Half of the participants received treatment and half placebo, with further stratification based on severity of disease, use of other medications, geographical region, and evidence of relevant genetic markers.

FDA approval on July 6, 2023 was based on 

indicating that the drug may slow progression of Alzheimer’s symptoms, as measured on global cognitive and functional scales. An FDA advisory committee had voted on June 9, 2023 that study results verified clinical benefit of Leqembi for its indicated use. However, the treatment will carry a boxed warning alerting patients and prescribers to the potential risks for individuals experiencing amyloid-related imaging abnormalities (ARIA) that may be associated with headaches, dizziness, as well as more serious brain edema. FDA recommends testing for a certain genetic marker that may be related to this condition.

Utilization and prescribing of the drug are uncertain, as many questions remain to be addressed concerning long-term effectiveness and prevalence and severity of side effects. And while Medicare and insurers will pay for much of the proposed $26,000 a year drug cost, patients will be responsible for considerable cost-sharing for the therapy, as well as a range of clinical visits and tests. At the same time, the relatively small positive effect on patient health may deter prescribing until additional data emerges. Utilization also may rise in the future with the development of new formulations that don’t require such frequent infusion, and more advanced diagnostics may better identify patients most likely to benefit and less likely to suffer serious side effects from the drug.

FDA's approval of Leqembi paves the way for wider coverage of the drug by Medicare and establishes a process for further clinical testing and evaluation of treatments for this widespread, debilitating condition

Large Clinical Trial Supports Alzheimer Drug Full Approval

FDA recently took the unusual step of approving the import of a widely used cancer drug from a Chinese manufacturer in the face of an outcry from physicians and patients over short supplies of vital oncology therapies. Although the regulators have revved up efforts in recent years to better prevent and address drug shortages, serious problems continue to plague drug production and distribution, particularly for a number of generic injectables.

National drug shortages rose in the first quarter of this year, according to the University of Utah Drug Information Service for the American Society of Health-System Pharmacists (ASHP) (1). Most of the serious shortages involve sterile injectables that are difficult to obtain quickly from alternative sources. FDA officials indicated they were looking for additional temporary suppliers of cisplatin, carboplatin, and methotrexate, all in short supply at cancer centers. FDA posted information on temporary importation of unapproved cisplatin from Chinese manufacturer Qilu Pharmaceuticals, to be distributed in the United States by Canadian-based Apotex Corp., on its drug shortages page on June 6, 2023 (2). FDA Commissioner Robert Califf noted in a social media message that the drug will come from registered facilities and will undergo careful assessment to ensure that the imported injectable chemotherapy is safe for patients.

Another example of FDA exercising regulatory flexibility is its decision to permit India manufacturer Intas Pharmaceuticals to export cisplatin and several other medically necessary injectable medications in short supply in the US, despite citation for multiple manufacturing deficiencies found during recent site inspections (3). FDA has required the company to provide third-party certification to confirm that products meet quality attributes and are not involved in data integrity violations. With the resumption of FDA plant inspections delayed by the COVID-19 pandemic, particularly with foreign facilities, the agency has uncovered more data and production quality issues that have led to import restrictions which have limited supplies.

Manufacturers are required to notify FDA in advance of anticipated production and supply problems, and the agency encourages industry to establish redundant production operations. But plant closures and problems in obtaining needed ingredients and supplies often cause supply reductions that can hit patients hard. Although FDA gained added authority during the COVID-19 pandemic to expand manufacturer notification of supply difficulties, notably for medical devices, some of these authorities are expiring. Legislation to strengthen reporting requirements for drug and medical devices makers have been proposed for inclusion in a measure to reauthorize the Pandemic and All-Hazards Preparedness Act, but dissension has delayed such efforts. Some legislators also want to revise the Controlled Substances Act to ensure patient access to ADHD treatment Adderall by better control of supply and preventing diversion.

FDA also would like to be able to require industry reports on rising demand for certain drugs, as occurred during the recent surge in respiratory infections. The agency currently lacks authority to collect this information and cannot compel any firm to produce more of a certain product. Brand manufacturers of new treatments, such as Novo Nordisk’s new weight-loss drug Wegovy, can better manage supply by taking steps to lessen demand, such as reducing supplies of a lower starting dose to discourage new patient treatment. Ideally, firms could respond to supply problems by shifting production lines to increase production of a needed medicine, but often are hampered by limited staff, resources, and ingredients. FDA recommends that manufacturers stockpile backup supplies of critical medicines, but, again, cannot require such action.

The broader problem is that shortages of cancer drugs and many widely used sterile injectables are produced by generic-drug manufacturers with limited redundancy in production due to very tight margins, as health plans and pharmacy managers push down prices. If a facility inspection uncovers serious quality issues or a company experiences increased costs for materials and operations, that may compel a plant shutdown that can impact the broader supply chain. In remarks at the annual meeting of the Biotechnology Information Organization (BIO) in June 2023, Commissioner Califf ascribed most drug shortages to generic-drug companies going out of business, either because they fail to invest in quality operations or because they can’t make a profit, as hospitals and pharmacies seek lower prices.

Such concerns were cited in a discussion of supply chain resilience at the Food and Drug Law Institute (FDLI) annual conference in May 2023, where a generic-drug maker warned against imposing added costs and burdens on industry, such as requiring production of extra supplies or stockpiles, due to unpredictable revenues from their commodity-like products. He advised against FDA’s proposed quality metrics requirements, which assume that purchasers will pay more for medicines from facilities that earn high quality ratings, a scenario that generics firms consider unlikely.

FDA described the challenges in coping with these issues in its latest report to Congress on drug shortages for 2022 (4). This annual update required by Congress since 2012 cites a decline in new drug shortages last year, but acknowledges still high ongoing shortage situations, as seen in the recent ASHP report. The agency continues to press for early notification of anticipated shortage situations to provide time to work with manufacturers to identify treatment options and to provide regulatory flexibility where appropriate. The report also describes increased collaboration with foreign regulatory authorities to identify supply chain disruptions involving overseas suppliers. FDA would like more information from manufacturers on supply chain components, such as inventory levels, and proposes to expedite the review and approval of generic-drug applications and supplements to address short supplies.

FDA. FDA Drug Shortages. Current and Resolved Drug Shortages and Discontinuations Reported to FDA. 

FDA. Letter to Mr. Nimish Chudgar, Intas Pharmaceuticals Limited. June 2, 2023. 

FDA. Report to Congress. Drug Shortages CY 2022. 

When referring to this article, please cite it as Wechsler, J. Drug Shortages Continue to Plague FDA and Manufacturers. 

Problems continue despite actions by regulators to better prevent and address drug shortages.