Jill Wechsler is ACT's Washington Correspondent

Jill Wechsler, ACT's Washington Correspondent

A detailed report from key House Committees blasts FDA’s role advising, assessing, and providing accelerated approval in 2021 for Biogen’s controversial Alzheimer’s disease 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 & Commerce Committee and the House Committee on Oversight & 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.

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 the limited evidence of treatment value and benefit. The Congressional report examines closely 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 pulling a product from the market.

The agency also addresses concerns about defining study requirements for drugs seeking accelerated approval in last year’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 amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, developed by Amylin Pharmaceuticals.

 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 deadline for granting accelerated approval for the drug after reviewing additional clinical trial results last year showing some benefit for Alzheimer’s patients.

 The sponsors also had to address safety issues following deaths of two, or possible more, patients enrolled in clinical trials. However, FDA declined in January to grant accelerated approval for Eli Lilly’s new antiamyloid, donanemab, instead requesting more long-term data from a larger ongoing clinical trial, most likely to support traditional approval.

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 FDA is going slow on speeding innovative therapies to market to avoid more criticism of its review process. The Center for Drug Evaluation and Research (CDER) approved only 37 new molecular entities (NMEs) last year, far below the usual 50 or more new therapies in recent years.

 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 (CBER) approved eight new therapies, including several new gene therapies and vaccines, but again fewer than in 2021.

 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.

https://energycommerce.house.gov/sites/democrats.energycommerce.house.gov/files/documents/Final%20Aduhelm%20Report_12.29.22.pdf

https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-option-patients-als

https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2022

https://investor.lilly.com/news-releases/news-release-details/us-food-and-drug-administration-issues-complete-response-0

https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2022-biological-license-application-approvals

Articles

House report on Aduhelm approval calls for FDA to clarify its role in advising sponsors on drug testing and submissions.

Congressional Probe of Alzheimer’s Drug Hits FDA Interactions with Industry

The year-end, must-pass government funding package includes multiple provisions important to FDA operations and authority, as well as for clinical research sponsors and pharmaceutical manufacturers. The $1.7 billion Consolidated Appropriations Act for 2023 will reshape Medicaid coverage and bolster pandemic preparedness and biomedical research, among dozens of measures involving drug development and regulation, as the legislators added hundreds of provisions sought by specific states and industries, but also left some key measures on the cutting-room floor.

FDA gains a notable funding increase, as well as multiple new policies and programs. The spending package provides the agency with a $6.6 billion total budget, a 6.5%, or $226 million, increase. That total includes $3.5 billion in appropriated funds plus $3 billion from authorized user fees paid by industry. A summary report from Senate and House Appropriations Committees specifies that the added funds should be used to help end the opioid crisis, expand foreign drug inspections, fund orphan product development, advance medical device cyber security, and expand agency data modernization, inspections, and other programs.

 FDA regulation of human drugs will have $760 million in funds, while the budget for biologics is $272 million, as seen in a chart from the Alliance for a Stronger FDA.

A leading provision overhauls FDA regulation of cosmetics to enhance product safety. To help states tackle the opioid crisis, the legislation aims to improve access to FDA-approved non-opioid therapies. Generic drugmakers gained provisions that prevent certain actions by brands designed to delay competition from generics and biosimilars. And to enhance diversity in clinical trials, the legislation instructs sponsors to submit “diversity action plans” for late-stage trials. FDA will issue more guidance on that process, hold public workshops on diversity issues, and report annually on progress in this area.

Probably the most high-profile FDA measure reforms the agency’s accelerated approval process. A key provision clarifies that agency reviewers may require that post-approval studies begin prior to product approval, but does not require FDA to do so. The measure also speeds up the process for withdrawing drugs that fail to confirm anticipated benefits, while stopping short of mandating such action. Sponsors must provide updates on confirmatory trial status to the agency every six months, and a new FDA accelerated approval oversight council will weigh in on policies.

Missing from the massive bill, however, is a controversial provision that would have confirmed FDA authority to regulate diagnostic tests developed in clinical labs, including those at hospitals and academic medical centers. Although medical device makers and federal regulators backed the change as a way to clarify FDA authority in this area, the proposed VALID Act (Verifying Accurate Leading-edge IVCT Development) continued to raise objections from the labs and clinics.

The massive spending measure provides significant added funding for veterans’ health care, while also saving billions by ending Medicaid expansion policies adopted during the pandemic. The lawmakers extend telehealth waivers for two years, continuing to support telehealth practices useful to a number of FDA programs.

The Biden administration’s Advanced Research Projects Agency for Health (ARPA-H) gains $1.5 billion funding and will reside in the National Institutes of Health (NIH). Various provisions clarify its governance, reporting requirements, leadership and collaborations with FDA.

The legislation further aims to enhance biosecurity programs to better prepare the nation’s capacity to combat future viral epidemics and biological threats. There is increased funding for the Biomedical Advanced Research and Development Authority (BARDA) and to expand the Strategic NationalStockpile. Added provisions support domestic production of certain antibiotics, further study on incentives for domestic production of generic drugs, and programs to enable rapid development and testing of drugs. A new White House Office of Pandemic Preparedness will oversee these efforts.

And vaccine makers and regulators will be following closely a measure setting the stage for an end to government subsidies for vaccines and medical products approved under emergency use authorization (EUA) policies adopted during the COVID pandemic.

A summary of the Consolidated Appropriations Act, 2023 is available 

https://www.appropriations.senate.gov/imo/media/doc/Division%20A%20-%20Agriculture%20Statement%20FY23.pdf

The Consolidated Appropriations Act for 2023 includes dozens of measures involving drug development and regulation. 


Massive Government Spending Bill Tackles Key FDA and Research Issues

This past year has been marked by continued efforts to develop, regulate, and distribute important therapies and vaccines to treat deadly and rare diseases, including the still dangerous COVID-19 virus. Despite generally high praise for biopharmaceutical companies in advancing these efforts, industry was unable to block the adoption of price controls for prescription drugs, a policy that risks limiting research in some areas. At the same time, the tense political environment leading up to the November mid-term Congressional elections blocked agreement on many important legislative and regulatory initiatives for FDA, delaying until the very last moment reauthorization of critical user fee programs to support the agency. Despite the anxiety generated by that cliff hanger, FDA succeeded in maintaining an efficient oversight and approval program for new and important therapies and issued multiple new guidances, renewed field inspections, and launched a range of initiatives to support public health.

On the R&D front specifically were pursuits from regulators and industry to advance novel approaches. A preferable strategy for pharma in curtailing drug prices, for example, is to achieve more efficient and less costly clinical trials, a goal that has prompted a range of initiatives to modernize biopharma research operations. The pandemic supported wider use of remote and online systems to enroll study participants and oversee treatment and patient status, with digital technologies becoming more widely used for patient monitoring. These approaches also appeared effective in advancing diversity among study participants, where remote site visits may facilitate enrollment of individuals facing difficulties traveling to clinical sites.

The ongoing surge in R&D for cell and gene therapies prompted a reorganization and expansion of FDA offices overseeing these products and efforts to clarify and update regulatory policies in this area. The importance of FDA providing individualized advice for these cutting-edge therapies highlights the critical need for the agency to attract experts to its staff able to oversee and encourage new methods and innovations.

The expansion in innovative biotech therapies and vaccines also highlighted the importance of modern production methods able to quickly ramp up production of new treatments. In 2022, FDA continued to advance several initiatives to improve product quality, including proposals for a quality management maturity program for drugs and biologics; appropriate oversight of products with limited chemistry, manufacturing, and controls (CMC) information due to expedited development treatment; and wider use of smaller, mobile drug production methods, such as distributed and point-of-care manufacturing.

FDA recognized the challenges in overseeing these developments as it moved to revive field inspection operations for manufacturing facilities and bioresearch operations. The agency indicated its intent to continue utilizing alternative remote inspection methods adopted during the pandemic based on the experience of inspection personnel in gaining needed information remotely on the status and compliance of sites, especially those with strong histories of meeting regulatory requirements. This shift to a dual inspection mode that incorporates document reviews and online “site visits” with real-time inspections is likely to become a permanent part of the agency’s oversight operations for manufacturers and clinical research operations in the US and overseas.

This past year was a difficult one for FDA Commissioner Robert Califf, who faced critical questioning and a long delay in gaining Senate confirmation to head the agency again after a brief time as commissioner in 2016. Califf came back to FDA with long experience in advancing the development and oversight of important new therapies to further combat global pandemics and deadly diseases. However, the commissioner had to spend much time and energy on a host of health crises, including a serious shortage in infant formula, rising death rates from opioid overdoses, and pressure to curb marketing of vaping products and e-cigarettes.

A serious challenge for Califf and health authorities is the continued rise in misinformation about coronavirus medical treatments and vaccines. FDA and other public health agencies struggled to boost COVID vaccination rates and counter anti-vaccine voices, while also combatting the promotion of untested and dangerous “treatments” for COVID and other serious health conditions.

Meanwhile, the delay in Congress renewing user fees for drugs, biologics, generic drugs, medical devices, and biosimilars hampered FDA planning and put multiple new programs on hold.

Pandemic Spurred New R&D Approaches from Pharma, FDA in 2022

While it may take weeks to know the final tally, neither Republicans not Democrats are expected to have more than a slim majority in the House or Senate, which reduces the likelihood of highly partisan legislation in the months ahead. The economy and inflation was a main concern driving voters to the polls, but it did not generate the predicted Red Wave to challenge Biden administration policies. At the same time, access to abortion was a prime issue, with voters supporting abortion rights ballot measures in five states. Even conservative voters opposed major reductions in health care, as seen in the vote in South Dakota to expand Medicaid coverage for low-income adults.

The situation makes it unlikely that Congress will tackle significant legislation during its lame duck session after Thanksgiving. Current members face a Dec. 16, 2022 deadline to approve an omnibus spending bill authorizing the federal government budget for 2023 to avoid a government shutdown. FDA would like the legislators to approve some of the measures dropped from the “slim” user fee reauthorization package approved in late September, but the calendar leaves little time for much debate. There’s a chance for approval of more tarted bills to revise FDA’s accelerated approval process, advance clinical trial diversity, clarify FDA inspection authority, and address cybersecurity in medical devices. But more complex measures to overhaul FDA regulation of in vitro diagnostics, cosmetics, and dietary supplements are likely to remain on hold until the new Congress convenes in January.

In the House, a shift to Republican control is most likely, setting the stage for GOP-led committees that will hold hearings and issue reports challenging a range of health care issues. FDA officials are likely to be called to Capitol Hill more often to explain actions related to the shortage in infant formula, difficulties in reducing deaths from opioids, its proposal to ban menthol cigarettes, and modified rules for accessing health care through video conferencing.

The Senate Health, Education, Labor, and Pensions (HELP) Committee is expected to have new leadership even if Democrats retain control. Chair Patty Murray of Washington may move to lead the powerful Senate Appropriations Committee, which leaves Bernie Sanders of Vermont as next in seniority. And with ranking Republican Richard Burr (R-NC) retiring, Sen. Rand Paul (R-KY) is in line to head the panel. Sen. Paul already is taking about committee investigations into the Biden administration’s inadequate response to the COVID-19 pandemic, with Anthony Fauci a prime target.

Republican promises to lower taxes and reduce inflation by slimming down federal spending raise uncertainties about support for future pandemic planning, replenishing national stockpiles of drugs and vaccines, expanding research at the National Institutes of Health and strengthening state Medicaid programs. A main target for GOP leaders is the Inflation Reduction Act (IRA), a prime initiative for the Biden Administration that featured a provision reducing consumer outlays for prescription drugs. Although Republicans criticize many aspects of the legislation, they are unlikely to have the votes to kill drug price negotiation authority for Medicare. At the same time, Republican leadership makes further drug pricing legislation unlikely, including proposals to curb pharmaceutical launch prices.

At the same time, Republican leaders are expected to press for changes in FDA policies to make it difficult for women to access approved abortions pills and to gain access to over-the-counter contraception. A main issue is slated to be FDA’s authorization of telemedicine visits for prescribing abortion pills, instead of requiring women to visit the doctor’s office. It also remains to be seen to what extent abortion foes question the right of pregnant women to access approved therapies for cancer and other lethal conditions that also could jeopardize the health of a fetus.

Following closely contested election, approval of FDA bills most likely tabled until new year.

Major FDA Reform Unlikely in Closely Divided Congress 

The long, convoluted FDA process to halt marketing of drugs that fail to confirm safety and efficacy in required postapproval confirmatory studies highlights the need to update and revise FDA’s now-controversial accelerated approval policy. This initiative has succeeded in speeding multiple important therapies to patients over the last 30 years. But the recent advisory committee vote to remove Makena from the market due to its failure to demonstrate benefits for patients illustrates how difficult it is for the regulators to ensure that such drugs document safety and effectiveness in a timely manner.

Makena was approved more than 10 years ago as a treatment to lower the risk of preterm birth in patients considered at-risk for miscarriage, but a confirmatory trial failed to support earlier results. Even so, Makena marketer Covis Pharma has opposed removal, asserting that the drug remains vital for certain high-risk patients. However, FDA’s independent expert panel voted 14-1 in favor of FDA’s decision to halt sales of the therapy, setting the stage for the agency to proceed with its lengthy effort to remove from the market an expedited drug that fails to confirm benefit.

The debate over accelerated approval ignited last year with FDA’s approval of Biogen’s Aduhelm to treat Alzheimer’s disease. That decision generated a range of reform proposals to ensure that sponsors conduct required confirmatory studies and release results. FDA’s Oncologic Drugs Advisory Committee (ODAC) also highlighted the issue at meetings in April 2021 and September 2022 challenging “dangling approvals” for cancer therapies, which prompted some manufacturers to withdraw certain indications and others to renew confirmatory study efforts.

A September report from the HHS Office of Inspector General (OIG) found that more than one-third of early approvals failed to meet timeframes for completing confirmatory studies, and that FDA’s difficulties in compelling withdrawals permit some therapies to stay on the market for years without verifying predicted clinical benefit, at considerable cost to insurers and Medicare and Medicaid. The OIG estimated that Medicaid spent about $700 million on Makena in recent years and said it was “crucial” to give FDA the tools to effectively administer the accelerated approval program.

Congressional leaders responded to FDA concerns by proposing legislation that requires sponsors to have confirmatory trials underway before gaining an early approval. Additional reforms aimed to facilitate FDA withdrawal of an approval if further study results fail to confirm efficacy within a certain period of time. These and other proposals initially were included in legislation to reauthorize FDA user fees, but were dropped to meet tight deadlines for Congress to approve the funding measure. Efforts continue on Capitol Hill to include accelerated approval revisions in proposed legislation, but a tight Congressional calendar dims prospects for enacting regulatory reform measures.

Stricter oversight of the accelerated approval program appears likely, though, as drug costs and benefits remain in the spotlight. Medicare’s decision to limit coverage of Aduhelm has prompted health plans and insurers to scrutinize more closely the costs and utilization of therapies with conditional approval status. Although anxious to retain the accelerated approval program, the cancer community and numerous patient disease groups recognize that FDA should be able to remove those products where sponsors are unable or unwilling to confirm initial efficacy. The “Project Confirm” initiative at FDA’s Oncology Center of Excellence (OCE) aims to pressure sponsors to provide postapproval data in a timely manner and to withdraw products from the market when postapproval studies fail to confirm benefit or are not completed with due diligence.

Despite the lack of alternative treatment to Makena for women at risk of miscarriage, FDA is under pressure to halt marketing of the drug to maintain confidence in the accelerated approval program, which was established 30 years ago and is credited with facilitating access to more than 300 treatments for cancer and serious conditions. More recently, FDA has taken action to revoke approvals of some 35 drugs, most for specific indications. Leaving Makena on the market, even for limited use, is opposed as likely to encourage other sponsors to delay confirmatory studies and flout agency rules to maintain profitable sales.

In a recent speech to the National Organization for Rare Disorders (NORD), FDA Commissioner Robert Califf acknowledged the wide benefits of FDA’s accelerated approval program in generating therapies to treat serious rare diseases. He also urged fast action to reduce uncertainty about the true risks and benefits of those therapies approved based on biomarkers and limited clinical trials. More collaboration is needed, Califf said, to establish a “system of evidence generation that provides the confirmation of benefits and risks over years.”

https://oig.hhs.gov/oei/reports/OEI-01-21-00401.asp

https://www.fda.gov/about-fda/oncology-center-excellence/project-confirm

https://www.fda.gov/news-events/speeches-fda-officials/remarks-fda-commissioner-robert-m-califf-2022-nord-breakthrough-summit-10172022

Potential drug removal spotlights latest debate over the expedited pathway.

Pressure Mounts for FDA to Reform Accelerated Approval Program

FDA’s Center for Biologics Evaluation and Research (CBER) is updating how it manages a growing volume of cell and gene therapy (CGT) development programs, seeking added resources and revisions in its oversight of these cutting-edge therapies. Most visible in the elevation of CBER’s Office of Tissues and Advanced Therapies (OTAT) into a new “super” Office of Therapeutic Products (OTP). The change aims to improve functional alignment, increase review capabilities, and add expertise on new CGTs by establishing multiple branches and divisions in the expanded regulatory unit, as announced in the Federal Register on Sept. 28.

Stated goals are to help CBER address the “substantial growth in innovative, novel products” that present new “scientific, medical, and regulatory challenges that require changes to its structure,” including strategies to advance the Regenerative Medicine Advanced Therapy (RMAT) program. The added resources are needed to oversee more than 2,000 development programs involving CGTs, many involving innovative testing and manufacturing processes. This soaring workload has overtaxed CBER staffers, resulting in serious difficulties in retaining and hiring capable scientists.

The structural changes at CBER reflect agreed-on plans to hire new staffers with funding from recently reauthorized user fee programs. The PDUFA VII commitment letter calls for an additional 132 new hires for CBER in this coming year and another 48 employees the following year, mostto support CGT reviews at OTP. The reorganization plan calls for OTP to have seven offices—for therapeutic products, clinical evaluation, review management, pharmacology/toxicology, and two for chemistry, manufacturing, and controls (CMC)—for gene therapy, cellular therapy, and human tissues. There will be 14 divisions and 32 branches within those offices, providing attractive supervisory opportunities for new and experienced staffers.

These changes come in the wake of FDA approval of two new gene therapies that have drawn wide attention for both their therapeutic potential and for million-dollar price tags. Bluebird Bio’s Zynteglo was approved by FDA in August for patients with beta thalassemia, an inherited blood disorder causing serious anemia. That was followed a few weeks later with approval of Bluebird’s Skysona to treat a rare neurological disorder afflicting young boys. Zynteglo carries a $2.8 million price tag, Skysona’s list price is $4 million, but both therapies are expected to target less than 1,500 patients, limiting the overall cost impact for the US healthcare system. A greater spending effect would come from FDA approval of a new treatment for sickle cell disease from Vertex Pharmaceuticals and CRISPR Therapeutics, which plan to begin a rolling review by FDA in the coming months. The important potential benefits of these treatments, along with concerns about their impact on healthcare spending and access, speaks to the need for a highly capable and sufficiently resourced FDA oversight program.

These developments also highlight the importance of sound testing and production methods for therapies made from living organisms, which are inherently variable and difficult to control and measure to assure product safety, identify, quality, purity, and strength. The surge in applications from a broad range of firms, moreover, has made it difficult for CBER staffers to schedule formal meetings with each sponsor seeking advice on how best to perform manufacturing and testing processes. And publishing new guidance on these changing and emerging issues also takes time and resources.

In response, FDA looks to engage a broad range of sponsors on topics related to product development through a series of virtual town hall meetings. The first was held Sept. 29 and addressed how manufacturers should describe and inform FDA about CMC in applications for gene therapies.

 Wilson Bryan, OTAT (now OTP) director, opened the session by describing plans for establishing OTP as a super office to increase review capabilities and enhance expertise on CGTs and set the stage for OTP branch chiefs to field a broad range of queries, ranging from basic CMC policies for various stages of development, to the scope of potency assays and impact of delivery devices on dose potency and quality.

Main topics were comparability testing, assays for product characterization, and process controls. OTP staffers emphasized the importance of determining process requirements early in development to avoid late changes and analytical method variability that could raise uncertainties likely to delay clinical trials. Products with complex mechanisms of action, they advised, stand to benefit from early product characterization and potency assay development. And developers of CGTs should use multiple production lots during a clinical study to ensure product consistency and quality, even for treatments for very small patient populations.

Manufacturers raised questions about differing CMC issues between early Phase I and late-stage clinical trials and voiced concerns about product characterization related to autologous cell-based gene therapies. A main theme from FDA was the importance of sponsors establishing a well-controlled manufacturing process and qualified analytical testing well before administering any new gene product. While CBER plans to issue guidance on manufacturing changes and comparability for CGT products, the information provided at this session provides unofficial guidance for implementing changes in product manufacturing and the scope of comparability assessments and development studies expected to support such changes.

https://www.govinfo.gov/content/pkg/FR-2022-09-28/pdf/2022-20997.pdf

https://www.fda.gov/news-events/otat-town-hall-gene-therapy-chemistry-manufacturing-and-controls-09292022

CBER maps modernization plan to handle surge in research and applications. 