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

Jill Wechsler

As expected, President Joe Biden used his annual 

this week to highlight the importance of efforts to lower the price of insulin and other prescription drugs to help seniors and all patients access needed care and to curb government spending. With the waning pandemic no longer controlling Americans’ lives, Biden outlined a host of priorities for improving health care and building the economy, and protecting Americans from excessive outlays for medicines was a prime strategy.

A main proposal is to extend the $35-a month cap on insulin spending for Medicare beneficiaries to all Americans. Biden noted that the Inflation Reduction Act (IRA) enacted in 2022 also capped annual out-of-pocket drug costs for Medicare patients at $2000 a year and predicted that the drug price negotiation provision in that legislation will further reduce Medicare outlays for medicines.

The President also called on policy makers to support extended Medicaid coverage for some 2 million people in states that have not expanded that program on their own. And he hinted at further White House efforts to challenge high launch prices for new drugs, particularly for life-saving, but costly, new gene and biotech thereapies. At the same time, Biden highlighted the importance of extending funding for his cancer moonshot initiative to reduce deaths from cancer, and he praised the President’s Emergency Plan for AIDS Relief (PEPFAR), a program launched 20 years ago by the Bush administration to combat HIV/AIDS around the world.

The focus on drug costs in this major national address indicates how important the issue is for advancing Democratic policies. And while Republicans in the House are not expected to approve any measure that further limits drug prices, Biden’s emphasis aims to fend off any efforts to roll back IRA provisions on this topic. Industry executives have proposed modifications in the terms governing the Medicare drug price negotiation program, but Senate leaders already are warning against such tactics. And Biden stated loudly that he would veto any measure likely to raise the cost of prescription drugs.

Industry’s main argument against drug cost-cutting measures is that price controls will dry up investment in R&D and reduce the range of important new therapies available to patients. Biopharma executives describe the Medicare drug price negotiation process as basically enforced price fixing on certain established medicines and that it will affect how companies allocate capital and force hard decisions on investments in the very costly process of drug testing and production. The 

Pharmaceutical Research and Manufacturers of America (PhRMA) emphasized

 industry’s contributions to advancing health, but predicted that Medicare price setting will limit incentives for developing new thereapies in certain areas and discourage further research on approved medicines.

PhRMA, however, has additional issues to worry about on the drug pricing front. A notable setback came a few days ago when a federal judge dismissed the drugmakers’ claim that a plan to expand the import of less expensive drugs from Canada established by the Trump administration would bring unsafe products into the United States. The 

federal district court in Washington, D.C. issued a decision 

stating that “such alleged harms” were not likely to materialize under the import proposal.

Articles

Biden outlined a host of priorities for improving health care and building the economy during State of the Union address.

Biden Hits Drug Prices for Boosting Health Care Costs

In announcing major changes to the agency’s oversight of foods and nutritional products, FDA Commissioner Robert Califf cited the need to “transform” the agency’s field inspection operation. The 

contemplated realignment of the Office of Regulatory Affairs (ORA) 

would better focus this vast organization on “critical activities” for ensuring the safety of foods and other regulated products, including drugs, biologics, and medical devices. And more unified oversight for human foods will aim to clarify lines of authority between FDA centers and the agency’s investigational force of some 5000 staffers in more than 200 offices and 13 labs around the country.

These changes come in the wake of an outcry over widespread shortages in infant formula supplies in 2022 due to product contamination that led to the shut-down of a major manufacturing facility and product recalls. Field inspectors complained that FDA food center officials failed to respond effectively to warnings of bacterial contamination at Abbott’s formula plant. In response, FDA now proposes to integrate programs that set food safety standards with operations to handle outbreaks and recalls under a new Deputy Commissioner for Human Foods, reporting directly to the Commissioner. The goal is to unify the various entities involved in oversight of food and nutritional products (including baby formula) into a single program, and to clarify relationships between field inspectors and headquarters in the process. Details were sparse, with FDA promising to provide more specifics on planned changes at the end of February.

The proposed changes will be tricky to accomplish, as Califf and Principal Deputy Commissioner Janet Woodcock indicated at a briefing with reporters on Jan. 31, 2023 to announce plans for the elevated foods center. Woodcock cited ongoing efforts to modernize the agency’s IT workflow management system to eventually establish a common platform for all regulated product centers to communicate with ORA, moving away from using multiple different systems for such interactions. Other initiatives involve establishing a clear inventory of the 600,000 various sites overseen by FDA inspectors and unifying state and local food safety partnership functions under the new program. But making significant changes in “how that all works,” Woodcock admitted, would be slow to come without additional resources.

Funding to expand or improve FDA’s food regulatory programs, however, suffers from limited budget appropriations and little support from industry-paid user fees. The Food Safety Modernization Act was adopted in 2011 in response to multiple food contamination outbreaks across the country, but only passed Congress by limiting penalties and fees on farmers and food processors—unlike the hefty fees paid by drug and biotech companies. The food industry provides FDA with a mere $10 million a year for facility reinspections, product recalls, and for certain food import activities. An added complication is that much of FDA’s food safety inspection work involves state and local officials, partnerships that Califf said will continue and will be strengthened.

Further realignment of ORA’s operating structure is not a new idea, as it was already implementing significant changes in how it oversees and enforces standards for drug, biologic, and medical product manufacturers when the agency had to make major adjustments in response to the global COVID-19 pandemic. ORA’s Program Alignment initiative for drugs and biologics aimed to move away from generalist inspectors to cadres of specialists trained to better evaluate the more complex medical products moving through the R&D pipeline. Then, as the spreading pandemic shut down travel and on-site plant visits, FDA shifted to virtual, remote oversight of manufacturers and research sites, limiting field inspections to “mission critical” applications and serious safety situations. Regulatory authorities also adopted more mutual recognition agreements with trusted foreign regulatory partners to share the burden of ensuring compliance of regulated facilities in their regions. FDA officials have indicated that many of these efficiencies may remain in effect even as the pandemic wanes.

Meanwhile, Califf’s announcement of the “key elements of a unified human food program” called for “reimagining” ORA but provided only a vague outline for changing operations by “improving risk prioritization,” “modernizing core operations,” and “creating operational efficiencies.” As noted above, more details to come. And while Califf noted that agency staffers support plans to update ORA operations, he and others acknowledged that more detailed discussion of any changes with the agency’s vast inspection cadre is necessary before making any changes.

Some policymakers want to split FDA into two entities, one overseeing food and another regulating drugs and medical products. That would require a big boost in federal funding for the two entities and further expansion and overhaul of the field force. And it ignites debate over where to put oversight of animal drugs, dietary supplements, tobacco, and other consumer products. Many safety experts and consumer advocates continue to press for more significant change at FDA, but this latest shuffling of operations may suffice.

A realignment of the Office of Regulatory Affairs would create a focus on “critical activities” for ensuring the safety of foods and other regulated products, including drugs, biologics, and medical devices.

FDA Food Center Reorg Puts Field Inspections in Limbo 

A detailed report from key House Committees blasts FDA’s role in advising, assessing, and providing accelerated approval in 2021 for Biogen’s controversial Alzheimer’s treatment Aduhelm (aducanumab). The critique calls for changes in agency interactions with manufacturers to more carefully document meetings and other communications and to clarify the agency’s role in advising sponsors on product testing and submissions.

The joint investigation by the House Energy and Commerce Committee and the House Committee on Oversight and Reform on FDA approval of Aduhelm slams FDA officials for failing to record multiple interactions with the company, particularly their assistance in developing Biogen’s briefing documents for a key advisory committee meeting (1).

The Democrat-led panels reviewed hundreds of reports and records that document how FDA formed a working group with the sponsor that engaged in dozens of meetings and more than 100 calls, email exchanges, and other interactions to review research data on the drug. The investigators report that FDA staffers helped Biogen revise its clinical trials and then surprised all observers with its decision to adopt the accelerated approval pathway for Aduhelm despite questionable efficacy data and opposition from some agency units.

Concerns about this unusual collaboration in developing and approving Aduhelm was compounded by Biogen’s high launch price for the drug despite limited evidence of treatment value and benefit. The Congressional report closely examines the company’s decision to set a price of $56,000 for treatment per year, along with its extensive plan for marketing the new drug and details on company board meetings to approve the program. In the end, Biogen’s strategy failed dismally, as the potential for huge outlays for Medicare beneficiaries prompted further assessment by the Centers for Medicare and Medicaid Services (CMS) that led to highly limited coverage of the drug and similar curbs on prescribing by insurers and health plans.

The House report calls on FDA to take actions to restore public “trust in the agency’s processes and assurances of drug safety and efficacy.” This includes fully documenting “all substantive FDA interactions with drug sponsors” and developing a protocol to address the preparation of joint briefing documents for advisory committees. The legislators also recommend that FDA update industry guidance for developing new Alzheimer’s drugs.

Meanwhile, FDA officials have revised the accelerated approval process by limiting time frames for manufacturers to conduct requested confirmatory studies and expanding efforts to remove from the market drugs that fail to document post-approval efficacy. The agency gained support for such action from provisions in the massive Consolidated Appropriations Act for 2023 designed to ensure that sponsors conduct required post-approval confirmatory studies in a timely manner. The legislation clarifies that FDA reviewers may require sponsors to begin post-approval studies prior to product approval and speeds up the process for the agency to withdraw from the market drugs that fail to confirm anticipated benefits in a timely manner. Sponsors must update the agency on confirmatory trial status every six months, and a new FDA accelerated approval oversight council will review the program and its policies and explain rationales for accepting confirming evidence, or for pulling a product from the market.

The agency also addresses concerns about defining study requirements for drugs seeking accelerated approval in 2022’s revisions to the Prescription Drug User Fee program (PDUFA), which clarifies the process for FDA and industry to assess likely requirements for post-marketing studies earlier in the development process. At the same time, FDA has intensified actions on drugs granted accelerated approval that fail to provide acceptable confirmatory evidence of product efficacy in a timely manner.

A big question is whether FDA will put off difficult approval decisions when facing questions about initial clinical data and uncertainty over post-approval assessment. Of note is a six-month delay last year in approving Relyvrio, a new treatment for ALS (amyotrophic lateral sclerosis or Lou Gehrig’s disease) developed by Amylyx Pharmaceuticals (2). Now all eyes are on FDA’s evaluation of additional Alzheimer’s treatments that target amyloid plaque in the brain, as with Aduhelm. First up was lecanemab from Eisai and partner Biogen (brand name Leqembi). FDA met its Jan. 6, 2023 deadline for granting accelerated approval for the drug after reviewing additional clinical trial results last year showing some benefit for Alzheimer’s patients (3). The sponsors also had to address safety issues following deaths of two, or possibly more, patients enrolled in clinical trials. However, FDA declined in January 2023 to grant accelerated approval for Eli Lilly’s new antiamyloid, donanemab, instead requesting more long-term data from a larger ongoing clinical trial (4).

Added concerns have been raised by the recent year-end reports of new drugs for 2022, which reveal a notable decline in innovative therapies gaining market approval. One interpretation is that the agency is going slow on speeding innovative therapies to market to avoid
more criticism of its review process. The Center for Drug Evaluation and Research approved only 37 new molecular entities (NMEs) last year, far below the usual 50 or more new therapies in recent years (5). The total includes 12 new cancer therapies and a range of treatments for skin conditions, diabetes, insomnia, and ALS.

In addition, the Center for Biologics Evaluation and Research approved eight new therapies, including several new gene therapies and vaccines, but again fewer than in 2021 (6). Analysts cite a broad range of factors shaping the new drug approval process, noting that important new rare disease treatments and innovative gene therapies advanced last year. Going forward, FDA will be under pressure to ensure that it fully considers risks as well as potential benefits of new therapies, and that its assistance in guiding drug development is impartial and transparent.

Staffs of the Committee on Oversight and Reform and Committee on Energy and Commerce. 

The High Price of Aduhelm’s Approval: An Investigation into FDA’s Atypical Review Process and Biogen’s Aggressive Launch Plans. 

House Committee on Oversight and Reform and Committee on Energy and Commerce. December 2022.

FDA Approves New Treatment Option for Patients with ALS

. Press Release. FDA.gov. Sept. 29, 2022.

FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment

Eli Lilly and Company. US Food and Drug Administration Issues Complete Response Letter for Accelerated Approal of Donanemeb. Press Release. Jan. 19, 2023.

2022 Biological License Application Approvals.


Vol. 47, No. 2
February 2023
Pages: 14–15

When referring to this article, please cite it as Wechsler, J. FDA Interactions with Industry Under Scrutiny. 

A Congressional probe of FDA’s approval of Alzheimer’s treatment targets the agency’s interactions with drug manufacturers. 

FDA Interactions with Industry Under Scrutiny

FDA just announced that it will restart in-person, face-to-face meetings with industry sponsors of drugs and biologics, beginning Feb. 13, 2023, after a shift to all-virtual meetings during the COVID-19 health emergency for nearly three years. However, the 

that it has revised its definition of such formal meetings to include both in-person and virtual components utilizing IT platforms that allow for both audio and visual communication. The agency explains that a face-to-face (FTF) meeting between FDA and industry will be a hybrid session, with both in-person and virtual components using cameras.

This redefinition of “in-person” meetings was agreed on in the recently updated user fee agreements for drugs (PDUFA VII) and biosimilars (BsUFA III). FDA also plans to apply this process to formal meetings involving over-the-counter medicines, even though that new user fee agreement does not specify this policy. For now, the agency will limit face-to-face hybrid sessions to requests for Type A meetings, Biosimilar Product Development Type 1 sessions, and Type X meetings, with other meeting types continuing to be fully virtual, without an in-person component.

FDA says it is in the process of updating guidance documents for formal meetings to include this revised definition and is highlighting the new meeting policy on its website to “help reduce uncertainties” for all parties. This dual approach for in-person meetings reflects a hybrid workplace format at the Centers for Drug Evaluation and Research (CDER) and Biologics Evaluation and Research (CBER), where many staffers still work only a portion of the time at FDA’s White Oak facility. The agency is upgrading its conference rooms there in phases to better handle hybrid meetings, a process that limits the number of in-person sessions that can be accommodated at this time.

To better manage the in-person component of these hybrid sessions, FDA plans to limit the number of people in the room to “core participants” (i.e., those with “primary speaking roles”) and encourages industry to do the same. Other staffers from both parties will join the session virtually. As FDA gains more upgraded conference rooms, it will consider phasing in additional types of meetings for in-person scheduling, such as Type A and Type B (milestone meetings), BPD Type 1 and Type 2, and Type X and Type Y. Eventually, all FTF formal meetings may be eligible for the in-person format.

FDA will restart in-person, face-to-face meetings with industry sponsors beginning Feb. 13, 2023, after a shift to all-virtual meetings during the pandemic.

FDA Resumes In-Person Meetings with Industry … Sort Of

A more harmonized formula and schedule for administering COVID-19 vaccines gained strong support from FDA’s expert advisory panel last week, with agreement on the need to reduce confusion over which shot to take and when in order to increase vaccination rates among both adults and children in the United States. The 21 members of FDA’s Vaccine and Related Biological Products Advisory Committee (VRBAC) voted unanimously for a more simplified approach, setting the stage for the agency to authorize a common bivalent shot for all patients that targets both the original COVID-19 strain and the Omicron subvariants. The new program would end use of Pfizer and Moderna monovalent vaccines that only target the original COVID strain.

FDA received less support for setting a schedule for annual vaccination against COVID, as the advisors expressed uncertainty about the effectiveness of the current shots and questioned what time during the year would be best for a national COVID vaccination campaign. Several panel members urged additional research on the effectiveness of the new formulations on frequently changing variants and the possible need for different vaccination schedules for both young children and older adults with health impairments. The experts called on FDA to provide additional data on vaccine effectiveness and timing to better determine whether all patients would need an annual shot.

The strategy to set a common formula for anti-COVID vaccines across the country aims to increase vaccination rates overall. New data from the Centers for Disease Control and Prevention (CDC) indicates that less than half of all older Americans (over age 65) have received the updated booster, and that vaccination rates are a meager 10% for children under age 4. The hope is that a shift away from differing vaccine compositions and varying immunization schedules, along with clearer alignment between US and European vaccination recommendations, will encourage more people to get such protection.

Pfizer, Moderna, and Novavax reported to VERBAC on efforts underway to produce reformulated bivalent vaccines and supported the plan to establish a common formulation for all manufacturers of the adopted shot to simplify vaccination recommendations and reduce patient uncertainty over effectiveness and safety of vaccines from different companies. The manufacturers emphasized the need for specifics from FDA on the process for updating vaccine strains, including the timing, process, and methodology for producing a data package for new licensure. While such filings are expected to include new preclinical and manufacturing data, sponsors opposed requirements for additional clinical trials, indicating that it will be more productive to assess post-authorization real-world data to confirm effectiveness.

FDA officials proposed to meet with the advisory panel in May or June to decide on which COVID strain to target in vaccines for later this year, anticipating a fast reformulation by manufacturers of messenger (mRNA) vaccines. But Novavax officials indicated that it might need to identify the strain earlier, probably in March, to produce a new vaccine by fall with its more traditional vaccine production process. All three shot manufacturers reported that they were already shifting to use prefilled syringes and single-dose vials, which are important for physicians, clinics and pharmacies planning to administer the new vaccines more widely in the wake of reduced federal government involvement in the program.

A related question is whether FDA will ask manufacturers to produce combination influenza/COVID vaccines to further simplify annual vaccination programs. The three firms reported that they are already studying such combination shots, but any shift towards such products will involve much further assessment of the need for and effectiveness of annual COVID vaccines or combination products.

While advisory committee experts and officials from FDA and other health agencies acknowledged the value of utilizing mRNA platforms to produce anti-COVID vaccines so quickly and effectively at the start of the pandemic, some panel members called for further research on how well the new formulations provide long-term protection and avoid safety issues, urging continued examination of whether more traditional vaccine production methods may have broader benefits moving forward. In its presentation, Novavax presented data indicating a “robust breadth of immunity” and strong manufacturing consistency for its more recently approved preventive.

In concluding the meeting, Peter Marks, director of the Center for Biologics Evaluation and Research, reiterated the need for a “data-driven approach” to achieve a vaccine regimen that is as simple as possible. But he also noted the importance of monitoring vaccine safety and assessing product effectiveness in shifting to a next generation of COVID vaccines able to provide “greater depth of protection.”

FDA plans to authorize a common bivalent shot that targets both the original COVID-19 strain and Omicron subvariants.

FDA Seeks to Simplify COVID-19 Vaccination Program

FDA has weighed into the escalating abortion policy battle by taking steps to expand patient access to the abortifacient mifepristone from pharmacies and physicians. The agency revised a regulation to enable local pharmacies to dispense the pill directly to individuals with a prescription, instead of requiring patients to visit a certified physician to obtain the drug. A related change also makes permanent its policy of permitting providers to prescribe the medicine via telemedicine visits.

In addition, the Department of Justice (DOJ) clarified that it is not unlawful for the US Postal Service (USPS) to deliver abortion drugs, even in those states with strict limits on pregnancy termination. In a 20-page legal opinion issued Dec. 23, 2022, 

DOJ affirmed that the mere act of mailing approved drugs 

does not violate the law. and that there may be circumstances even in states with strict curbs on abortion where the use of such medication is permitted. USPS had asked DOJ for guidance on the issue as efforts expanded to deliver abortion pills through the mail in states with strict abortion curbs following the Supreme Court decision in June 2022 striking down established federal rights to abortion.

FDA revised its dispensing policy for mifepristone by altering certain provisions of its Risk Evaluation and Mitigation Strategy (REMS) for the drug. The change was requested by manufacturers Danco Laboratories and GenBioPro, which produces a generic version. Under the revised REMS, chain and independent pharmacies that become certified in the program may dispense the drug directly to patients presenting a prescription from a certified prescriber, as explained in FDA’s review of the 

Danco, which has produced mifepristone for 20 years, praised the FDA policy change, noting the critical importance of its product in providing a “safe and effective option for ending early pregnancy” at a time when people across the country 

“are struggling to obtain abortion care services.”

 The manufacturer explains that FDA modified the prescriber and patient agreements in the Mifepristone REMS and added a new pharmacy agreement, noting that it will phase in these changes over several months to avoid disruptions in dispensing mifepristone by current providers in clinics and hospitals.

In addition, FDA aims to make it easier for patients to obtain a prescription for mifepristone by making permanent its temporary health access policy change in 2021. The agency had cancelled the “in-person” requirement that patients physically visit healthcare providers to obtain a prescription for the abortion drug, a restriction originally backed by abortion foes seeking to limit access to the drug.

Despite these FDA policy changes, women in states with strict abortion curbs still will have to travel to other states to obtain mifepristone from a drug store. At the same time, major pharmacy chains may not rush to become certified to dispense abortion pills. And the clarification that it’s legal to mail abortion pills is not expected to facilitate mail delivery in states with highly restrictive policies.

The REMS revision and FDA’s support for telehealth prescribing puts the agency squarely in the center of the escalating debate over access to medicated abortion, which now accounts for half the abortions in the United States. Already, lawsuits have challenged FDA’s original approval of mifepristone for ignoring safety issues, and the new policies are expected to generate a wave of legal actions from anti-abortion groups and state agencies, as well as citizens’ petitions seeking more restrictive FDA labeling on the these products.

Jill Wechsler is Washington reporter for 

The agency revised a regulation to enable pharmacies to dispense mifepristone directly to individuals with a prescription.