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

Jill Wechsler

	Under pressure to expand public access to new medicines, diagnostic tests, and other medical products needed to detect and treat patients struck by COVID-19, FDA has issued more than 100 Emergency Use Authorizations (EUAs) since early February, compared to fewer than 75 during the 10 previous years. While this activity reflects the imperative for fast action by federal agencies and manufacturers to address the pandemic crisis, it also generates questions about the vetting of these requests and how well FDA can follow up with sufficient tracking of the safety and efficacy of these products. And some observers fear that political interference in the process may erode confidence in the scientific basis for FDA regulatory decisions.

 to use an unapproved drug or medical product, or an approved drug for additional uses, in an emergency when there are no adequate, approved and available alternatives . Most of this year’s EUAs are for diagnostics and medical products needed to augment national resources for testing individuals for contamination. Some EUAs facilitate use of innovative technology, as seen in 

 for a new saliva-based COVID-19 test that would permit wider at-home sample collection and for the first antigen test, which promises to be less costly and more rapid in detecting the virus. Some EUAs involve new respirator cleaning systems and innovative protective personal equipment.

	Only two EUAs this year are for therapeutics. FDA issued an EUA May 1, 2020 to Gilead Sciences to permit limited use of the investigational drug remdesivir to treat very ill COVID-19 patients. Here the emergency authorization was approved after a clinical trial provided evidence of some effectiveness in highly critical situations. As expected, the EUA limits the drug’s use to hospitalized patients with severe COVID-19 disease, while clinical testing continues.

	More controversial is FDA’s approval of an EUA to permit the use of certain widely available malaria drugs to treat COVID patients, despite concerns from medical authorities about no data supporting effectiveness against the coronavirus and the risk of serious adverse effects on individuals with certain heart conditions. Even so, FDA issued an EUA for chloroquine and hydroxychloroquine on March 28, 2020 to permit use of drugs in the Strategic National Stockpile (SNS) but only for distribution to health professionals treating hospitalized patients with confirmed COVID-19.

	Despite such limitations, FDA continued to draw criticism for acceding to political pressure from the White House to enable broad use of these drugs. But in an interview posted on STAT on April 24, 2020, Center for Drug Evaluation and Research (CDER) Director Janet Woodcock explained that permitting access to some three million pills donated by Bayer and others augmented short supplies that undermined approved treatment for lupus and rheumatoid arthritis, and that FDA tested the donated drug, which came from uninspected manufacturing facilities in India, extensively for quality. Woodcock maintained that the EUA does not undermine FDA review standards and that the 

such emergency use does not represent approval of the drug for a new use.

	Woodcock is supported by subsequent revelations about the political infighting leading up to this EUA. The lengthy 

filed May 5, 2020 by Rick Bright, director of Health and Human Services’ (HHS’) Biomedical Advanced Research and Development Authority (BARDA), details efforts by Bright and others to prevent widespread use of hydroxychloroquine as a supposed preventive and cure for COVID-19. Bright recounts how HHS officials initially pressured BARDA to establish a nationwide Expanded Access Investigational New Drug (IND) protocol for chloroquine, which would make the drug available outside the hospital setting and without close physician supervision, but that Woodcock provided support for an EUA from FDA with restricted uses.

	In response to these developments, Sens. Elizabeth Warren (D-Mass) and Patty Murray (D-Wash) 

 more closely FDA’s role in enabling rapid emergency use of drugs, biologicals, and devices and the agency’s ability to track adverse events and other outcomes related to such authorizations. In a letter sent May 6, 2020, the legislators request information from FDA Commissioner Stephen Hahn on FDA arrangements with manufacturers and healthcare facilities to collect data on adverse events and outcomes, what actions FDA can take if these entities fail to provide such information, and whether FDA needs additional authorities to revoke EUAs and recall relevant products.

	Meanwhile, FDA faces challenges in continuing to evaluate hundreds of EUA requests. The agency website on EUAs notes that some 385 diagnostic test developers plan to submit EUA requests for tests to detect the coronavirus. And, now with the emergence of evidence that Gilead’s remdesivir may offer greater benefits to very ill patients, demand for chloroquine has diminished, leaving hospitals and clinics with millions of unneeded pills.

Articles

Some observers fear that political interference in the process may erode confidence in the scientific basis for FDA regulatory decisions. 

FDA’s Emergency Use Process Under Scrutiny

 Century Cures Act, including provisions to advance research related to the COVID-19 crisis as part of initiatives for bringing innovative therapies to market faster. A 

for a Cures 2.0 legislative package was recently unveiled by Reps. Diana DeGette (D-Col) and Fred Upton (R-Mich), who sponsored the Cures bill of 2016. It calls for a national COVID-19 testing and response strategy, with specifics for developing and administering vaccines and therapeutics and for modernizing and expanding US biopharma manufacturing capacity to provide needed treatments for patients on a timely basis.

	Cures 2.0 continues and updates some of the main themes of the first Cures Act: support development of treatments for rare diseases, patient-focused drug development, diversity in clinical trials, expanded use of digital health systems, increased health literacy, and utilization of real-world data. FDA guidance would clarify methods for collecting post-market real-world evidence for products approved under accelerated approval pathways, and federal grants would support organizations that aide patients with rare diseases to facilitate patient participation in clinical trials. A public education campaign, moreover, would aim to counter concerns about the safety of vaccines to promote widespread vaccination.

	Another goal is to boost industry investment in developing new antibiotics. Because these treatments are costly and unprofitable for biopharma companies to test and market, the legislation proposes additional financial support for both for pre-market studies and post-market production and subsidized higher reimbursement rates for antibiotics that address critical needs.

	Federal government reimbursement and coverage for important new therapies would advance through earlier communication on upcoming breakthrough drugs by FDA and the Centers for Medicare and Medicaid Services (CMS). The final bill aims to outline additional proposals for modernizing CMS coverage policies, particularly related to reimbursement for cell and gene therapies and treatments for very small patient populations.

	To further promote diversity in clinical trials, the new Cures legislation also supports efforts to modernize the Clinical Trials.gov website to make it easier for patients to identify studies open to enrollment. The aim is to make it easier for individuals to search for relevant studies and to understand enrollment criteria and study requirements. The National Library of Medicine (NLM) at the National Institutes of Health (NIH) has launched a 

for the 20-year-old CT.gov website, with the aim of streamlining and clarifying the process for trial sponsors to list and update study data and for patients to search for and retrieve desired information. A range of proposals were discussed last week at a NLM 

 on the ClinicalTrials.gov modernization effort.

	Reps. DeGette and Upton also back a proposal to boost federal support for academic and independent medical research centers and laboratories that have been slowed or shuttered by the pandemic. A group of more than 150 lawmakers 

 Congressional leaders to provide $26 billion in an anticipated fourth COVID-19 relief package to support important biomedical research programs. The funds would help fund researcher salaries, core research facility operating costs, and fellowships and research grants, as part of a strategy for preserving US scientific infrastructure and protecting innovation.

	Similarly, some of the Cures 2.0 provisions related to advancing research and regulatory policies designed to combat COVID-19 may be enacted more quickly as part of additional pandemic support legislation. Even so, the sponsors aim to introduce the full legislative package this year in order to gain enactment before Congress is under pressure to debate and approve the next FDA user fee renewal legislation in 2022. 

Congressional leaders are developing the next version of the 21st Century Cures Act, including provisions to advance research related to the COVID-19 crisis as part of initiatives for bringing innovative therapies to market faster.

Second “Cures” Bill Promotes Pandemic Preparedness

	Concerns about access to medicines and diagnostics critical to containing the coronavirus pandemic (COVID-19) and treating infected patients have broadened support for advanced pharmaceutical manufacturing and test methods. FDA officials have long pressed industry to adopt continuous manufacturing and online testing methods able to scale up quality production quickly and efficiently. The current pandemic has boosted support for such initiatives, as global health organizations and US policy makers recognize the importance of being able to produce millions of doses of any promising new treatments.

	While the lack of personal protective gear and respirators has dominated the headlines since the pandemic outbreak, potential difficulties in ensuring sufficient supplies of newly discovered therapies and anticipated vaccines have moved to center stage. China’s prominence in producing key APIs for antibiotics and many common medicines, plus a recent move by the Indian government to halt the export of multiple drugs and drug ingredients, heightened concerns about the United States’ dependence on global supply chains. Rumors that an existing malaria treatment might be effective against COVID-19, for example, created a run on the drug, leading to notable shortages at some manufacturers.

	These concerns have spurred calls for greater US investment in high-tech biopharma production systems. In announcing the COVID-19 Therapeutics Accelerator in early March to advance treatments for the pandemic, the Bill and Melinda Gates Foundation cited the need to quickly build up manufacturing capacity to test a variety of drugs. Gates further emphasized that the federal government should provide suppport for building production facilities now, as making such investments before knowing that a product will be used is excessively risky for manufacturers.

	Funds to advance efficient drug manufacturing systems to ensure access to vital therapies and prevent shortages due to supply disruptions from China and elsewhere were included in the initial $8.3-billion emergency coronavirus funding package enacted March 5, 2020. FDA gained $61 million to support the development of new medical countermeasures and vaccines, of advanced manufacturing for medical products, and for monitoring medical product supply chains (1). The subsequent $2-trillion coronavirus aid and relief package approved March 27, 2020 similarly provided an added $80 million to FDA to advance the development and approval of medical countermeasures and vaccines (2). The legislation also directed FDA to use some of the funds to further the adoption of advanced manufacturing systems for medical products and to monitor supply chains for potential threats to access to medicines and APIs imported from abroad. To help FDA anticipate looming supply problems, Congress instructed manufacturers to send FDA information on where interruptions in supply affect APIs as well as drugs and extended such requirements to medical device makers during this public health emergency. To further address these issues, Congress provided $1.5 million for the National Academies of Sciences, Medicine, and Engineering (NASEM) to prepare a study on ways to strengthen the manufacturing supply chain for drugs and devices to avoid shortages.

	Added support for establishing advanced biopharma manufacturing facilities is found in sections of the pandemic relief legislation, which provides some $30 billion for federal health agencies to develop countermeasures and vaccines, plus platform technologies to advance US production of new therapeutics, diagnostics, vaccines, and medical supplies. Congress specified that a portion of $3.5 billion for the Biomedical Advanced Research and Development Authority (BARDA) should be used to construct or renovate US-based next-generation manufacturing facilities. Similar directions are included in providing added funds for the Defense Research Advanced Projects Agency (DARPA) in the Department of Defense, building on its research programs related to advancing biopharma manufacture. Among other things, these initiatives have supported the development of RNA and DNA vaccines to fight infectious diseases such as Chikungunya and Ebola and to overcome manufacturing challenges to faster scale-up.

	The pandemic legislation also provides $27 billion for the Public Health & Social Services Emergency Fund managed by the Secretary of Health and Human Services (HHS) to develop countermeasures and vaccines in response to the pandemic. This includes building the Rapid Aseptic Packaging of Injectable Drugs (RAPID) consortium with a network of up to eight domestic facilities to rapidly fill and finish millions of prefilled syringes for delivering vaccines and therapies for COVID-19 (3). An innovative syringe developed by ApiJect Systems utilizes existing blow-fill-seal technology plus an interlocking needle hub to provide low-cost, easy-to-use injectables for the Strategic National Stockpile.

	Similarly, additional funding for the National Institute of Standards and Technology (NIST) supports programs to accelerate production of critical materials, build additional production facilities, ensure supply chains for vital ingredients, develop and train manufacturing workers, and return to the US the manufacture of critical conventional drugs (4). NIST has worked with biotech firms for several years to address challenges in developing more efficient and reliable ways to produce high quality cell and gene therapies.

	These and other projects stand to assist manufacturers on accelerated timelines for testing promising COVID-19 therapies and vaccines looking to establish systems for fast, reliable manufacturing scale-up capabilities. At a “virtual summit” in March sponsored by the Biotechnology Innovation Organization (BIO), industry leaders cited the challenge in needing to expand manufacturing capabilities before knowing they have a viable product, and the fast launch of clinical trials for candidate vaccines aggravates those difficulties.

	On many fronts, industry is rising to the challenge, with pharma companies partnering with smaller biotechs and federal agencies that offer innovative drug and vaccine candidates for established firms to test and produce. In March, Johnson & Johnson announced that a $1-billion partnership of its Janssen unit with BARDA planned to rapidly scale up vaccine manufacturing capacity to be able to supply over one billion doses of vaccine globally (5). Such fast expansion of production capacity will be needed for clinical trials slated to begin this fall and then to provide emergency use access to any promising product.

	1. H.R. 6074, 116th Congress, Public Law 116–123-Mar. 6, 2020, 

Coronavirus Preparedness and Response Supplemental Appropriations Act

Amendment H.R. 748, “An Act to amend the Internal Revenue Code of 1986 to Repeal the Excise Tax on High Cost Employer-Sponsored Health Coverage

,” US Senate, March 21, 2020.
	3. HHS, “HHS Announces New Public-Private Partnership to Develop US-Based, High-Speed Emergency Drug Packaging Solutions,” Press Release, March 18, 2020.
	4. NIST, “NIST Funding Manufacturing Institutes to Support Pandemic Response,” Press Release, March 31, 2020.
	5. J&J, “Johnson & Johnson Announces a Lead Vaccine Candidate for COVID-19; Landmark New Partnership with US Department of Health & Human Services; and Commitment to Supply One Billion Vaccines Worldwide for Emergency Pandemic Use,” Press Release, March 30, 2020. 


	Volume 44, Number 5
	May 2020
	Pages: 14–15

	When referring to this article, please cite it as J. Wechsler, "Modern Drug Manufacturing Key to COVID-19 Response," 

Policy makers seek to ensure supplies of new therapies and to limit shortages.

Modern Drug Manufacturing Key to COVID-19 Response

	With hundreds of clinical trials for potential coronavirus therapies in the works-and even more in development-concerns have mounted about the emergence of conflicting data, useless results, and wasted efforts from multiple overlapping efforts. In response, the National Institutes of Health (NIH) 

 a broad public-private partnership (PPP) to collaborate on prioritizing and coordinating research on COVID-19 drug and vaccine candidates. The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative has support from a number of federal agencies, and some 16 pharma and biotech companies are participating through the Foundation for the National Institutes of Health (FNIH).

			Multiple websites identify and track research on COVID therapies and vaccines			

					Widespread research activity is available from these and other organizations:    

	NIH Director Francis Collins emphasizes the importance of bringing “unassailable objectivity” to swiftly identify the most promising compounds from multiple stakeholders. Those priority therapies should gain fast and efficient regulatory oversight and vetting, moreover, through the involvement of FDA and the European Medicines Agency (EMA) in the partnership.

	This initiative builds on earlier efforts, such as the 

 launched in March by the Bill & Melinda Gates Foundation to drive collaboration among drug makers, regulators, and non-governmental organizations. In addition, more than a dozen biopharma companies 

to share public information on research efforts, while several international organizations are coordinating clinical trials and developing master protocols.

	The new NIH-based partnership appears poised to advance collaborative research more extensively, with industry and government partners providing infrastructure, subject matter expertise, and funding to identify top priority candidates for advanced testing. FNIH will manage an ACTIV steering committee to develop an inventory of potential candidates, launch master protocols with a single control arm, and set criteria for ranking potential candidates for first wave and subsequent evaluation. Another sub-group will set standards for preclinical evaluation methods through a central repository to assess models, extend high-throughput screening facilities, and compare approaches for identifying informative assays. And a third group will tap NIH’s extensive clinical trial network infrastructure to build capacity for expediting trials and to study different populations and disease stages.

	To advance vaccine development, another ACTIV group will form a collaborative framework to map epitopes and develop assays, establish protocols for sampling and immunological analyses, collect clinical data on immunological responses and endpoints, and engage with regulators on surrogate endpoints for clinical evaluation.

	ACTIV’s initial goal is to select six to eight compounds for clinical trials that assess different mechanisms of action, Collins explained in a 

sponsored by the Duke Margolis Center for Health Policy.  He noted that the working groups met in early April to start the process of identifying the highest potential therapies, particularly those where manufacturing scale-up won’t be a major roadblock. The candidates will include anti-virals with well-established mechanisms of action, immune therapies, and immune suppressants for patients with advanced lung disease.

	Establishing “really organized clinical trial capacity” is critical to be able to slot promising compounds into networks utilizing master protocols, Collins emphasized. Even if current studies of existing therapies such as remdesivir show benefit, he predicts a strong need for combination therapies going forward.

	FDA is deeply engaged in all these working groups to ensure that the group’s clinical studies will meet regulatory standards. And it’s all moving “at rocket pace,” Collins observed, with the goal of identifying two to three promising therapies by July or August for further testing in the fall. A main benefit of this initiative, he noted, is that “all stakeholders are together around the table.” Biopharma companies are “not just pushing their own candidates,” he noted, and are offering clinical trial capacity “to get this done.”

With hundreds of clinical trials for potential coronavirus therapies in the works concerns have mounted about the emergence of conflicting data, useless results, and wasted efforts from multiple overlapping efforts. 

More Coordination Sought for Exploding COVID-19 R&D Efforts

	Efforts to shift more production of pharmaceuticals and APIs to the United States as a strategy for reducing drug shortages and ensuring access to needed medicines has gained strength in the White House and on Capitol Hill. The recent $2-trillion COVID economic stimulus legislation, which provides billions in assistance to US industry and individuals losing jobs, also supports exploration of federal “Buy American” policies, ostensibly to reduce US dependence on drugs and medical products imported from overseas.

	One proposal advanced by the Trump Administration to encourage more domestic pharmaceutical production would apply domestic sourcing requirements to federal agencies that pay for large volumes of pharmaceuticals, such as the Departments of Defense, of Veterans Affairs, and Medicare and Medicaid. The government also could provide tax incentives and loans to firms looking to establish operations at home.

	Leading this initiative is White House trade advisor Peter Navarro, a long-time advocate for strong protectionist policies and now involved in administration efforts to coordinate access to needed medical supplies. Navarro’s prominence in administration pandemic response efforts has upset those policy makers who fear that the Buy American campaign will spark a trade war over government procurement requirements and would run afoul of international trade agreements for accepting bids from foreign suppliers. More troubling is that other governments would respond by curbing exports of medical products, particularly new effective treatments and vaccines to combat COVID-19.

	A main factor in the debate is that many drugs and most of their ingredients are imported to the US, largely from India and China. The proportion is even higher for APIs and many widely used, but critical, generic drugs, such as antibiotics. Recent shortages of sedatives required for patients on ventilators has become a crisis at many hospitals. Meanwhile, political leaders in India blocked the export of certain drugs and pharmaceutical ingredients, and other governments similarly look to protect domestic supplies of medical equipment. US–China trade disputes in recent years raise questions about whether the US will be at the top of the list of nations seeking to import any effective COVID vaccine developed in Chinese labs. Some biopharma companies racing to test and gain approval of effective COVID treatments and vaccines have announced plans to expand production in the US, moves that may reflect requirements imposed in R&D funding agreements that involve US research agencies.

	Drug manufacturers, distributors, and dispensers 

 as likely to reduce reliable supplies and raise product costs. A coalition of brand- and generic-drug makers, pharmacies, distributors, and patient advocates raised these concerns in a March 27, 2020 letter to President Trump, claiming that proposals to “drive all manufacturing to the United States” overestimate the feasibility of making such changes and underestimate the time and effort it would take. A diverse pharmaceutical supply chain is “precisely what enables the industry to respond quickly and make adjustments” in product sourcing during emergencies and global public health crises, the group states. Conversely, Buy American requirements could destabilize the supply chain for pharmaceuticals and medical devices and undermine “complex arrangements between firms” that support efficient delivery of medicines to patients.

	Similarly, another group of pharmacists, insurers, and brand and generic manufacturers raised objections 

in letters to Vice President Mike Pence and Republic and Democratic leaders of the House and Senate

. The coalition noted that a contemplated Buy American executive order could have “an immediate and detrimental impact” on access to medicines, particularly for individuals in federal health programs. Instead, the government should issue national clinical guidelines to clarify the appropriate use of existing and new medications to avoid individual stockpiling that can lead to shortages. And federal officials should work with airlines to ensure reasonable shipping costs of critical medicines to maintain supplies of needed medical products amidst wide cuts in air freight transport.

	FDA has long required pharma companies to provide advance notice of anticipated shortages of critical medicines, and the recent extension of such reporting requirements to APIs and certain medical devices should fill some information gaps. Those provisions reflect growing concerns in Congress about FDA’s limited oversight of the rising volume of foreign-made drugs, which frequently have raised quality and safety issues over recent years. FDA has long urged manufacturers to adopt advanced manufacturing systems that would support less costly and more efficient drug production, and several Senate and House legislative proposals further such efforts and policies to help reduce industry’s heavy reliance on APIs from China.

	But drugs and ingredients made in the US are likely to be more expensive and carry higher price tags, particularly for medicines facing shortages or rising demand. And even low-cost generic- drug makers face strong push-back from price increases, particularly in short-supply situations.

Drug manufacturers, distributors, and dispensers oppose Buy American policies as likely to reduce reliable supplies and raise product costs. 

Buy American Proposals Rile Manufacturers and Trading Partners

	The 10th anniversary of the enactment of the Biologics Price Competition & Innovation Act (BPCI) in March 2020 has focused attention on the advances made over the past decade and main challenges ahead. Despite general disappointment over the slow pace of consumers gaining access to less costly biotech therapies, new FDA guidance and clarified policies provide added support for biosimilar development and approval, particularly for diabetes treatments. FDA also has teamed up with the Federal Trade Commission (FTC) to counter anticompetitive practices that thwart development and raise concerns about biosimilar safety and effectiveness.

	A positive sign is that the pace of FDA approvals of biosimilars has picked up in recent months, with more than 26 approved products as of early February 2020-10 approved in 2019-and more than a dozen competitors on the market. In addition, the World Health Organization has begun to prequalify biosimilar versions of “essential medicines” to make these treatments more available and affordable in less developed countries.

	An important FDA initiative aims to encourage manufacturers to prepare the data needed to support applications for follow-on versions of insulins now deemed to be licensed as biologics and thus eligible for competition from biosimilar or interchangeable therapies. In February 2020, FDA issued a final rule defining the new process, as established by the BPCI and revised in legislation to clarify that the deeming process applies to insulin, human growth hormone, and most proteins-specifically any alpha amino acid polymer with the specific, defined sequence greater than 40 amino acids in size (1). The new rule aims to “bring down prices and help patients have access to more choices for these life-saving drugs,” said FDA Commissioner Stephen Hahn. FDA also issued explanatory documents for consumers (2) and physicians (3) to clarify that treatments approved under the new program will be just as safe and effective and accessible as brand insulin reference therapies.

	Efforts to bring insulin competitors to market builds on FDA guidance issued in November 2019 outlining a streamlined development pathway for these long-established therapies (4). That advisory proposes reduced clinical immunogenicity studies for products that present strong comparative analytical assessments demonstrating high similarity to the reference drug, and no residual uncertainty regarding immunogenicity. In May 2019, FDA provided detailed advice on designing and evaluating such analytical studies and on providing scientific and technical information for the chemistry, manufacturing, and controls (CMC) portions of an application for a biosimilar in draft guidance (5). At that same time, FDA published long-awaited guidance on developing interchangeable biosimilars, again noting the importance of analyzing critical quality attributes and identifying analytical differences between the reference product and the proposed interchangeable (6). 

	The FDA–FTC initiative further aims to encourage prescribing and reimbursement for biosimilars by taking aim at “misinformation” campaigns backed by brands to discourage biosimilar uptake. The regulators outline how they will work together to promote competitive markets for biological products that “contribute significantly to drug costs,” noted Commissioner Hahn (7).

	The two agencies also offered to help biosimilar makers gain ready access to samples of reference products needed to develop and test follow-ons-a difficulty that also has plagued the broader generic-drug industry. And FTC is taking a close look at patent settlement agreements involving biologics and biosimilars to detect any antitrust violations. A joint public workshop held on March 9, 2020 addressed these efforts and other strategies to build a more competitive market for biological products.

	In a related move, FDA also published guidance in February 2020 outlining the process for seeking FDA approval of a subset of approved indications of a reference product. This approach applies when patent and exclusivity provisions may prevent a newly licensed biosimilar from including all indications of a reference product on the label, a situation that often involves pediatric or orphan disease treatments. But once those limitations expire, FDA encourages the follow-on manufacturer to file a supplemental application with data supporting the expanded uses, as seen in an advisory outlining how data and labeling should be presented to add previously omitted conditions of use (8). FDA says it will review such supplements within six months, much faster than the usual 10-month timeframe set for supplements to biologics license applications (BLAs).

	And to ensure that promotional messages related to biosimilars by both brands and competitors are truthful, non-misleading and balanced, FDA draft guidance issued Feb. 3, 2020 instructs brands to avoid implying in its messages that a reference product is safer or more effective than an approved biosimilar, or that the follow-on is “not highly similar” to the reference product, even if the competitor is not licensed for all indications (9). The guidance emphasizes that a biosimilar product is not required to be identical to the brand to be licensed, but just that it be “highly similar” and without “clinically meaningful differences” in terms of safety, purity, and potency. An added proposal is that the FTC take antitrust action against brand manufacturers that make misleading claims to counter competitions.

, Feb. 21, 2020.
	2. FDA, Information for Patients About Regulatory Changes for Certain Biological Product Medications, 

, undated, accessed March 5, 2020.
	3. FDA, Information for Health Care Providers About Regulatory Changes for Certain Biological Product Medications, 

 undated, accessed March 5, 2020.
	4. FDA, 

Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products, Draft Guidance

Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations, Draft Guidance

Considerations in Demonstrating Interchangeability with a Reference Product, Guidance for Industry

 (CDER, CBER, May 2019).
	7. FDA, “FDA and FTC Announce New Efforts to Further Deter Anti-Competitive Business Practices, Support Competitive Market for Biological Products to Help Americans,” Press Release, Feb. 3, 2020.
	8. FDA, 

Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use for Which the Reference Product Has Been Licensed, Draft Guidance

 (CDER, CBER, February 2020).    9. FDA, 

Promotional Labeling and Advertising Considerations for Prescription Biological Reference and Biosimilar Products, Questions and Answers, Draft Guidance


	Vol. 44, No. 4
	April 2020
	Pages: 14–15

	When referring to this article, please cite it as J. Wechsler, "Biosimilars Poised for Gains in US Market," 

FDA is encouraging alternative insulins and challenging anticompetitive practices.