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

Jill Wechsler

	Scott Gottlieb has seen a whirlwind of activity since taking the helm of FDA in May 2017. He blasted brand manufacturer “shenanigans” for blocking generic-drug development and cited “pernicious” rebating schemes that expose consumers to high out-of-pocket costs for medicines. To help mitigate the nation’s deadly prescription drug epidemic, he has backed policies to reduce opioid prescribing and to develop less addictive pain treatments. And to continue last year’s notable gains in bringing important new drugs and gene therapies to market, Gottlieb has promoted innovative clinical research methods and other strategies to make drug testing more efficient. 

 that he is revving up FDA efforts to encourage industry conversion to advanced manufacturing systems able to scale up quickly to address public health issues. New policies to ensure quality manufacturing can facilitate the development of competitive biosimilars and prevent shortages of critical medicines to protect public health. 

	These and other initiatives have quieted critics on all sides. Democrats initially feared an industry bias but have been impressed by the commissioner’s criticism of drug pricing and his campaign to reduce nicotine in cigarettes. Republicans hoping for a free-market deregulator admire his efforts to combat opioid abuse and his support for innovation to speed new medicines, devices, and diagnostics to patients. Certainly, many of Gottlieb’s initiatives are not new and reflect years of hard work by FDA’s professional staff. But vocal support from the commissioner has accelerated action on many fronts. 

	A clear achievement is a proposed $400-million boost in FDA’s budget for 2019, as compared to the administration’s plan to cut agency appropriations by $700 million a year ago. The commissioner has gained support for FDA in Congress, which helped enact crucial user fee reauthorizations last year and blocked the Department of Defense from taking control of approving new treatments for the military. FDA also negotiated some modifications in “right-to-try” legislation to lessen its erosion of the FDA approval process and maintain patient protections. 

	To convince the legislators to approve FDA’s new budget plan, Gottlieb outlined proposals for utilizing added resources (1, 2). Several initiatives advance the testing and production of new therapies, including greater use of real-world evidence and knowledge management systems to facilitate regulatory decisions, particularly for new treatments for rare diseases. 

	FDA also highlights the importance of modernizing drug manufacturing in proposing to spend $35 million to produce novel technologies, vaccines, and personalized medicines more reliably and at lower cost.  Gottlieb now sees a convergence in regulatory resources, industry frustration with traditional production methods, and wider availability of new technology to advance more reliable and flexible advanced and continuous manufacturing systems. 

	“We’re now at a tipping point,” says Gottlieb. The agency will develop further guidance and standards to reduce uncertainty for industry in adopting high-technology platforms. And more highly trained field investigators will inspect for quality and those aspects of manufacturing that create risks, Gottlieb explains, and move away from a checklist system for uncovering violations. Further innovation may come from FDA funding of advanced manufacturing R&D projects to assess new quality manufacturing and analytical methods (3). 

	This focus on quality manufacturing fits well with Trump administration efforts to encourage “re-domesticating some of the manufacturing that has moved overseas,” Gottlieb explains. He notes that high-quality, small-footprint manufacturing platforms have lower labor costs more suited to US operations. Advances in how FDA oversees medical device production similarly bolsters a “bring medtech manufacturing home” initiative that encourages firms to re-tool manufacturing processes in the United States. And streamlined oversight of software-based devices aims to lower the time and cost of market entry. 

	FDA also seeks to build the largely domestic pharmacy outsourcing industry through clearer manufacturing standards and policies. And more modern production methods for biologics are on the agenda to improve the agility, flexibility, and reliability of manufacturing processes for vaccines and cell and gene-based therapies. In the wake of this year’s severe influenza outbreak, Gottlieb has urged shifting from an egg-based to cellular system for seasonal flu vaccines, along with efforts to develop a universal influenza vaccine to provide multi-year protection, and ensure US access to vaccines to protect against a pandemic.  

	More advanced manufacturing methods also support more reliable production of biosimilars. Gottlieb plans to issue new guidance documents on reducing lot-to-lot variability over time for biologics by utilizing new tools better able to identify where lot variation raises potential risks to patients, along with more standard reference products that are easier to test and copy as biosimilars. 

	Despite a year of considerable success in broadening support for FDA initiatives and policies, the commissioner shows no sign of slowing down. He continues to tackle controversial issues, such as limits on flavored nicotine products, oversight of independent testing labs, and programs to limit food contamination outbreaks. The commissioner has emphasized the importance of promoting vaccination rates, despite continued opposition from vaccine deniers. And in another speech, he outlined plans to implement nutrition labeling standards and menu disclosures, which Gottlieb considers key to improving public health (4). 

	FDA also faces numerous deadlines for implementing key provisions of the 21st Century Cures legislation, including policies to support regenerative medicine and to speed the development of new cancer therapies, personalized medicines, and gene therapies. At the other end of the spectrum is a press for more efficient oversight and approval of over-the-counter medicines through a new user-fee program. And transparency remains a thorny issue, as FDA supports wider disclosure of data and analyses related to regulatory, safety, and enforcement decisions. Yet proposals for release of complete response letters remain on hold, as industry seeks to keep confidential certain regulatory decisions. 

	Combating the opioid epidemic is a prime challenge. While FDA supports the development of safer and more effective pain therapies and treatments for substance abuse and is re-examining the safety of abuse-resistant products, physicians are pushing back on proposals to limit opioid prescribing. FDA has gained added funds to expand its capacity to block imports of unlawful controlled substances at the border, and new legislation may strengthen its authority to require small-dose packaging of opioids and to remove from the market approved pain medicines found to raise safety issues. 

	Gottlieb plans to remain a visible advocate for lower drug prices, anticipating a continued roll-out of incremental changes to create a more competitive prescription drug market place. He has loudly criticized drug reimbursement and coverage policies for limiting consumer access to drugs, including a “rigged payment scheme” that blocks biosimilars, and suggested that FDA may be more flexible in setting standards for demonstrating product interchangeability (5). 

	The commissioner’s concerns about the high cost of medicines reflect his own experience as a physician and seeing ill patients “struggling very hard at the worst moments in their lives” to try to afford drugs that are “absolutely indicated for their disease.” He wants to be sure “that in my time here at FDA, I do something to address that.” 

	1. FDA, “Statement from FDA Commissioner Scott Gottlieb, MD, on Administration’s Request for New FDA Funding to Promote Innovation and Broaden Patient Access through Competition,” 

, Feb. 13, 2018. 
	2. FDA, Department of Health and Human Services Fiscal Year 2019, Food and Drug Administration, 

Justification of Estimates for Appropriations Committee

. 
	3. FDA, Agency Announcement, Solicitation Number: FDABAA-18-00123N, 

, Feb. 14, 2018, 
	4. S. Gottlieb, MD, “Reducing the Burden of Chronic Diseases,” 

, March 29, 2018.
	5. S. Gottlieb, MD, “Capturing the Benefits of Competition for Patients,” 


	Vol. 42, No. 5
	May 2018
	Pages: 14–16

	When referring to this article, please cite it as J. Wechsler, "Gottlieb Tackles Tough Issues in First Year at FDA" 

Articles

FDA’s commissioner addresses opioid abuse, drug costs, and manufacturing quality.

Gottlieb Tackles Tough Issues in First Year at FDA

	A lethal influenza outbreak this past winter has spotlighted the importance of improving and accelerating vaccine discovery and production. Reports that this year’s flu vaccine was only 36% effective have raised concerns about continued use of egg-based production systems that appear outdated and less reliable. And the imperative to combat infectious disease outbreaks and deadly conditions such as malaria and tuberculosis emphasizes the need to modernize and streamline vaccine testing and manufacturing. 

	A source of optimism is continued development of new, more effective inoculations. In 2017, FDA’s Center for Biologics Evaluation and Research (CBER) approved GlaxoSmithKline’s new Shingrix vaccine against shingles and a new recombinant hepatitis B preventive from Dynavax Technologies featuring a new adjuvant to boost immune response. A 

 from the Pharmaceutical Research and Manufacturers of America (PhRMA) in late 2017 lists 264 vaccines in development, including 137 for infectious diseases and more than 100 for cancer (1). And while vaccines are expensive in the United States, costs in low- and middle-income countries are dropping as regional producers such as India’s Bharat Biotech gain World Health Organization (WHO) prequalification for important preventives. 

	Vaccine discovery, however, remains challenging and unpredictable for the biomedical research community and industry. Even though increasingly effective vaccines are eliminating diseases such as polio and diphtheria and helped stem the Ebola outbreak three years ago, promising candidates often fail. Sanofi recently halted distribution of its dengue fever vaccine in the Philippines after some patients developed the disease following injection (2). 

	Such setbacks fuel anti-vaccine campaigns around the world, as seen in attacks on inoculation programs to combat a yellow fever outbreak in Brazil and on measles vaccines in the United States and Europe. Rumors of health risks continue to discourage vaccination of teens against human papillomavirus (HPV) despite evidence that it can prevent cancer. 

	FDA Commissioner Scott Gottlieb, MD, voiced strong support for vaccines at his Senate confirmation hearing in April 2017, where he dismissed as groundless claims of a causal link between vaccines and autism, distancing himself from earlier challenges to vaccine safety by President Trump. In an announcement of spending priorities for 2019, Gottlieb highlighted the importance of advancing manufacturing technologies for drugs and biologics, including vaccines. He

that continuous manufacturing platforms can help ramp up vaccine supply on short notice and that FDA clarification of its requirements and standards should encourage industry investment in new technologies and opportunities (3). 

	FDA support is important in maintaining an efficient development and review process to deliver vaccines that meet high standards to ensure product safety and quality. FDA is applying lessons learned from Ebola to streamline vaccine development, noted Philip Krause, deputy director of CBER’s Office of Vaccine Research & Review (OVRR), at the January 2018 WCBP symposium in Washington, DC. Krause emphasized how FDA strives to review and approve submissions and manufacturing supplements in a “sensible” way that emphasizes good science. CBER also encourages manufacturers to meet with FDA staff to address chemistry, manufacturing, and controls (CMC) issues before filing an application.

	Robin Levis, deputy director of OVRR’s Division of Viral Products, further described how FDA’s Fast Track and priority review programs facilitated development of Ebola vaccines and other preventives. To keep pace with accelerated clinical testing of potential Ebola preventives, FDA collaborated with other regulatory authorities and WHO to gain convergence on key issues, such as exceptions to product characterization and testing procedures, and where certain aspects of process validation could be abbreviated. While FDA licenses only those vaccines supported by adequate and well-controlled studies and able to be manufactured in a consistent manner, Levis noted that there may be flexibility when combating epidemics, such as accepting supportive CMC data from platform-related products and specifications based on related products. Test vaccines also may be used prior to obtaining real-time stability data, especially for early clinical trials. 

	An accelerated pathway for vaccine testing, however, “puts the squeeze on the CMC window” for process definition, characterization, and qualification, commented Natalie Christian, integrated development and supply team lead at Merck, at the January WCBP symposium. Vaccine development may be even more challenging, she observed, due to limited platform technologies for these products, potential for process change during technology transfer, scale-up difficulties, and a need for additional qualification lots. Similarly, Cristiana Campa of GSK Vaccines in Italy emphasized that the complexity of vaccine development makes it important to define a control strategy for identifying critical quality attributes as early as possible to help screen and select adjuvants and to identify attributes to be tested in clinical studies. 

	Advances in designing small footprint, single-use bioreactors will provide vaccines quickly at greatly reduced cost, predicted Benjamin Damien, director of business development at Belgium-based Univercells. He said these developments will “transform the biopharmaceutical industry” by boosting local production and supply of high-quality vaccines in developing countries, while also expanding capacity for rapid response to epidemics and global threats. 

	Many of these initiatives have support from the Bill & Melinda Gates Foundation, which has led efforts for the past decade to spur vaccine development to combat global diseases. To enhance the process, Gates established the Medical Research Institute (Gates MRI) in Boston to work closely with scientists and biopharma companies on identifying, selecting, and optimizing production of novel vaccine candidates. Gates veteran Penny Heaton is building the MRI with the aim to eradicate malaria, accelerate the end of the tuberculosis epidemic, and prevent diarrheal deaths in children through developing new drugs, vaccines, biologics, and diagnostics. Heaton outlined plans at the WCBP symposium for supporting early clinical testing of products that then can be passed on to manufacturers for late-stage development and commercialization. She anticipates a strong focus on CMC issues, which she described as often the “number-one bottleneck” in vaccine development.  

	Meanwhile, the race is on to discover a universal flu vaccine that doesn’t require reformulation every year. A dozen candidates are undergoing preclinical and clinical testing at research institutions and commercial labs. This coincides with efforts to shift from egg-based to cell-based and recombinant DNA production technologies. In commenting on the effectiveness of this year’s flu vaccine, 

 that products made with cell-based methods appear more effective in protecting against the H3N2 virus than egg-based products (4). 

	Seqiris, a unit of Australia’s CSL, plans to produce 20 million flu vaccine doses this year using cell culture at its North Carolina facility, and Sanofi has linked with South Korean vaccine maker SK Chemicals to tap its cell-based vaccine production technology. A live attenuated intranasal FluMist vaccine from AstraZeneca’s MedImmune division, an alternative to painful sticks, is back on the US recommended list after a two-year suspension due to data indicating low efficacy.

	Despite the shortcomings of annual flu vaccination, health authorities continue to stress the importance of regular immunization to prevent thousands of deaths from influenza each year, particularly in children and the elderly. Hopefully, the research community will devise a more reliable and effective universal flu vaccine before the next, much-feared influenza pandemic strikes. 

	1. A. Powaleny, “New Report and Event Examine the New Era of Vaccines,” 

	2. Sanofi, “Sanofi Updates Information on Dengue Vaccine,” Press Release, Nov. 29, 2017.

	3. FDA, Statement from FDA Commissioner Scott Gottlieb, M.D., on 

Administration’s Request for New FDA Funding to Promote Innovation and Broaden Patient Access through Competition

	4. FDA, Statement from FDA Commissioner Scott Gottlieb, M.D. on the 

Efficacy of the 2017-2018 Influenza Vaccine


	Vol. 42, No. 4
	April 2018
	Page: 16–18

	When referring to this article, please cite it as J. Wechsler, "Modern Manufacturing Key to More Effective Vaccines," 

Accelerated development of new preventives raises challenges for efficient CMC evaluation and production.


Modern Manufacturing Key to More Effective Vaccines

	After months of delay, Congress finally passed a $1.3-trillion omnibus budget bill March 22, 2018, just in time to avoid another government shut-down. The measure increases federal support for biomedical research and health programs for fiscal year 2018, which began months ago.

	A major winner in the funding measure is the National Institutes of Health (NIH), which saw its budget increase to $37 billion. Additional support is provided for research on Alzheimer’s disease, the brain research initiative, precision medicine, antibiotics, cancer, and developing a universal flu vaccine.

	FDA also gained $41 million in added appropriations, largely to improve food safety programs, enhance the Oncology Center of Excellence, and bolster programs governing animal drugs and feed, according to 

analysis by The Alliance for a Stronger FDA

. FDA also will be able to tap $94 million to expand its role in combating opioid abuse, particularly FDA operations to detect and block imports of illegal drugs. And the agency gains access to $60 million more to support implementation of the 21

	Despite the big increase in federal funding for many programs, the measure disappointed the healthcare community by failing to include provisions to stabilize Affordable Care Act marketplaces. Insurers predict that this omission will boost health insurance premiums noticeably just before the November 2018 Congressional elections. The spending measure also did not address contentious immigration issues or fund a border wall, prompting President Trump to threaten to veto the bill before signing it into law.

	Pharmaceutical companies suffered a notable loss in failing to convince Congress to alter an earlier legislative change that increased their liability for covering the Medicare Part D donut hole. In a budget deal approved in February, the legislators approved a measure that boosts the discount manufacturers pay to 70% from 50% to patients in the coverage gap, adding about $40 billion in costs to drug companies over 10 years. 

	And despite an additional $3.6 billion to address the opioid crisis, this was far less than the $10 billion requested by public health officials. Most of the funding increase will support substance abuse treatment. In addition, the legislation provides $3.2 billion for mental health programs, a notable increase. This budget runs through September 2018, when Congress is scheduled to approve the administration’s budget plan for 2019.

Congress passed a $1.3-trillion omnibus budget bill March 22, 2018 that increases federal support for biomedical research and health programs for fiscal year 2018. 

Budget Bill Boosts Funding for Biomedical Research and FDA Programs

	“Pernicious” rebating and contracting schemes and “Kabuki drug-pricing constructs” expose consumers to high out-of-pocket costs for biosimilars and actively discourage competition from these more affordable alternatives, says FDA Commissioner Scott Gottlieb. As part of FDA initiatives to reward innovation and promote patient access to medicines, the agency is working hard to support the development of high-quality biosimilars and interchangeable products, he explained at a policy conference sponsored by America’s Health Insurance Plans (AHIP) in Washington, DC on March 7, 2018. But high rebates paid by brand manufacturers to health plans and pharmacy benefit managers (PBMs) make it hard for biosimilars to compete. And Gottlieb feels that this reduces incentives for a biosimilar maker to make the investment needed to develop lower-cost biologics.

	FDA has approved nine biosimilars, but only three are on the market due to a range of obstacles. Manufacturing and testing biosimilars currently costs from $100 million to $250 million per program, much more than the $10 million involved in developing a generic version of a small-molecule drug. Consequently, biosimilars come to market at prices only 15–20% below the innovator, which often is not a big enough difference to drive reimbursement and prescribing.

	The crux of the problem is the “rebate trap,” Gottlieb explained. This permits PBMs and insurers to “profit from the spread between Wholesale Acquisition Cost (WAC) and the actual rebated price” for an innovator therapy. Rebates can amount to hundreds of millions of dollars in annual revenues for PBMs and insurers, and typically are tied by manufacturers to volume or preferred formulary status. Such strategies make it costly for plans to shift patients from an established drug to a biosimilar without losing substantial rebate payments.

	Competitive health plans often use rebates to lower premiums in order to compete in the market, and not to offset beneficiary co-pays, Gottlieb added. So, the recent decision by United Healthcare to pass along full drug rebates to more than seven million people in its fully insured plans drew praise from the commissioner as a move that could help more patients afford needed medicines.

	As biologics account for an increasingly large portion of drug outlays, Gottlieb urged payers and insurers to reject rebate arrangements that can discourage biosimilar development. Plans can further encourage biosimilar use by lifting prior authorization requirements for biosimilars, designing formularies with biosimilars the default option for newly diagnosed patients, and waiving co-insurance on these products.

	To support biosimilar development, FDA seeks to provide greater scientific and regulatory clarity for sponsors, a more efficient review process, and tools for using modern analytical techniques. The agency is evaluating how smaller, targeted clinical trials may help bring biosimilars to market in a more cost-effective and timely manner and other strategies that will be spelled out in a new Biosimilar Access Plan.

	FDA also will offer more education for clinicians and patients on the safety and efficacy of biosimilars to address concerns or misconceptions that foster reluctance to prescribe and use these therapies. And it will do more to lay out an efficient path for biosimilars to demonstrate interchangeability with brands.

	A global market for biosimilars will create efficiencies, Gottlieb noted, and FDA is working with regulatory authorities in Europe, Japan, and Canada to harmonize R&D requirements and share experiences in overseeing biosimilars.

	These efforts appear to be paying off, with 60 biosimilars for 27 different reference products enrolled in FDA’s Biosimilar Development Program. Another sign of progress is that biosimilar competitors to Neupogen have captured nearly 50% of market share, saving payors $150 million annually.

	Yet, Gottlieb fears that without more transparent pricing practices, biosimilar uptake will remain slow, and potential competitors will be scared off. Insurers and payers must decide if they want to continue to benefit from profitable rebates, Gottlieb stated, or “help generate a vibrant biosimilar market that can help reset biologic pricing.”

The FDA commissioner outlined the agency's initiatives to reward innovation and biosimilars development.

FDA's Gottlieb Hits Innovators, Insurers for Blocking Biosimilar Uptake

	Secrecy and black-box operations are out; public disclosure is the mantra for regulators and manufacturers alike, as FDA explores more options for communicating agency policies, approval decisions, and concerns about product quality and safety. The drive for greater transparency in agency decision-making fits a range of health policy goals. More information on drug pricing, discounts, and rebates is considered key to limiting payer and patient outlays for prescription drugs. The Federal Open Payments, or “Sunshine”, policy tracks industry payments, gifts, and transactions with healthcare professionals to uncover any industry influence on prescribers. And more timely and complete information on product safety and recalls aims to prevent patient harm, as do efforts to make drug labeling more informative.

	A main transparency issue involves public access to clinical study data and results. While industry sponsors of clinical trials are meeting requirements for listing new studies on the ClinicalTrials.gov website, the record is weaker for timely posting of research results for newly approved medical products. The data transparency movement also has prompted biopharma companies to provide scientists and researchers with access to confidential clinical research data and to limit publications to open access journals. Meanwhile, academic researchers have lagged in disclosing clinical research activities, prompting the National Institutes of Health (NIH) to threaten to cancel grants to organizations that fail to meet requirements. 

	Transparency also is considered important for enhancing drug quality to reduce product recalls and shortages, according to a white paper from the 

 (OPQ) in the Center for Drug Evaluation and Research (CDER) (1). As part of efforts to encourage manufacturers to adopt continuous manufacturing and systems to better ensure quality, an OPQ pilot study is exploring strategies with potential to enhance the transparency and consistency of assessments and facilitate team-based review and communication. 

	Other nations are joining the transparency movement. The China Food and Drug Administration (CFDA) issued draft guidance on policies for disclosing information regarding the acceptance, review, and approval of drug applications. While aiming to keep trade or technical data confidential, CFDA will make public information on active ingredients, dosing, license holder, and patents 60 days following an approval. 

	Despite expanded information disclosure related to biomedical research, drug marketing, and product safety, stakeholders want to know more about the status of drug applications and FDA’s decision-making process in both rejecting and approving submissions. A main demand-from both consumer activists and free market deregulators-is for access to complete response letters (CRLs) sent to manufacturers that essentially delay or reject an application and outline what additional clinical or manufacturing information is needed to achieve approval. FDA currently posts summaries and reports on newly approved drugs and biologics and has indicated interest in also posting CRLs. But manufacturers strongly oppose such a move as CRLs usually contain trade secrets or confidential information. Current law requires FDA to redact such manufacturing information from public disclosures, and any move to change that policy may require legislative action. 

	These issues are not new and reflect decades of reviewing and updating FDA policies on public access to information on agency operations and regulated products. A Transparency Initiative launched in June 2009 under former FDA Commissioner Margaret Hamburg and former Principal Deputy Commissioner Joshua Sharfstein has established FDA online “dashboards” that track agency actions and programs, including inspections, recalls, imports, and compliance actions. A “Drug Trials Snapshots” initiative posts data from clinical trials on products approved since January 2015. FDA has expanded access to agency enforcement reports and adverse event data and has made its guidance development process more visible and efficient.

	Last year, Sharfstein, now affiliated with the Johns Hopkins Bloomberg School of Public Health, organized a group of experts to produce a Blueprint for Transparency at FDA, which was published March 2017 in a special issue of the 

(2). Among its 18 recommendations for making FDA decisions less opaque, the Blueprint calls for FDA to provide more public information on its evaluation process for new drugs, generics, and biosimilars, including what products are in the review queue and why certain applications are not approved. The rationale is that discussion of unsuccessful R&D would help researchers avoid studies unlikely to succeed, reducing costs and avoiding patient exposure to potential harm. The analysts also seek authority for FDA to correct misleading information issued by manufacturers, such as incomplete factors underlying a CRL, and for the agency to disclose data from clinical trials for approved products when sponsors fail to do so. 

	Such proposals reflect greatly expanded public access to information on drug testing and production through the Internet, social media, and smart phones-not all of it accurate or unbiased. Consumers and industry competitors can obtain reports of adverse events and enforcement actions, raising questions about the value and impact of limits on what FDA can or cannot disclose about a product or manufacturer. 

	FDA Commissioner Scott Gottlieb addressed these issues at a January 2018 forum on the Hopkins transparency report. He 

 a new pilot to test the impact of FDA posting more data from clinical study reports (CSRs) of approved drugs, asking that sponsors of nine new products voluntarily provide CSR data, protocols, and statistical analysis plans for pivotal studies (3). In addition, FDA aims to better track drug studies from initial Internet posting through FDA approval by adding the ClinicalTrails.gov identifier (NCT) number to all clinical data submitted to the agency. 

	However, Gottlieb hedged about publishing CRLs, proposing to further explore FDA’s authority to release these documents. While he acknowledged that some information in CRLs might enhance the safe use of already approved products, he noted that redacting proprietary information from these letters is burdensome and questioned the value of disclosing letters that cite manufacturing shortcomings.

	Gottlieb also mentioned FDA efforts to inform the public more quickly about adverse events and product recalls, which totaled more than 9000 in 2017, including 1200 involving drugs.  Up until now, FDA has delayed recall announcements until it determined whether a safety issue raises serious health consequences, as with a defective anesthesia product, or represents low risk. Now FDA’s Office of Regulatory Affairs (ORA) will include in weekly Enforcement Reports “not-yet-classified” recalls while the months-long classification process continues. FDA issued

 in January 2018 outlining when a manufacturer should issue a public warning about a recall, including timelines and important data to include and what information FDA will post in its reports (4). 

	Although FDA has authority to require recalls, most drug manufacturers initiate such actions voluntarily, aware that FDA can issue press releases and alerts if companies are slow to act. Recall announcements from companies seem to appear almost weekly, many involving particulates or contamination of sterile injectables. Unfortunately, the failures that lead to drug recalls often create shortages in needed medicines. FDA and manufacturers will be looking to see if the earlier recall listing process generates alarms that turn out to be unnecessary, or if the new policy gets high-risk products off the market more quickly.  

Office of Pharmaceutical Quality, FDA Pharmaceutical Quality Oversight, One Quality Voice

, Special Supplement to Vol. 45 (4) 7-23  (Winter 2017).
	3. S. Gottlieb, “

Fostering Transparency to Improve Public Health

Guidance for Industry: Product Recalls, Including Removals and Corrections 

(Office of Regulatory Affairs, Nov. 3, 2003).


	Vol. 42, No. 3
	March 2018
	Pages: 14–16

	When referring to this article, please cite it as J. Wechsler, "FDA Heightens Drive for Transparency," 

Manufacturers face demands for timely information on clinical studies, product recalls, and approvals.

FDA Heightens Drive for Transparency

	FDA advocates on all sides applauded the request to increase funding significantly for FDA under the Trump administration’s budget for fiscal year 2019, which seeks more than $400 million in additional outlays for oversight of drugs, biologics, and medical devices. The Alliance for a Stronger FDA praised the budget plan for recognizing the important work of FDA in advancing innovative drugs and medical devices, while Friends of Cancer Research noted the $20-million allocation to support FDA’s Oncology Center of Excellence, which had not received full funding previously.

 seeks $5.8 billion in total resources for FDA, with $3.25 billion coming from federal appropriations and the rest from 

. The $473-million increase is the largest boost in public funding ever for the agency, according to the Alliance. The administration also advises FDA to use its resources to speed the approval of more new generic drugs, support development of new diagnostics and abuse-deterrent drugs to fight the opioid epidemic, modernize over-the-counter drug regulation, and advance therapies, vaccines, and devices to counter public health emergencies and disease outbreaks.

	At the same time, the medical research community raised concerns about resource reductions for other health and research agencies. The National Institutes of Health (NIH) faces cuts under this latest plan, despite the appearance of a funding increase; most of any added funds come from shifting other parts of the Department of Health and Human Services (HHS) into NIH, including the Agency for Healthcare Research and Quality (AHRQ). The Centers for Disease Control and Prevention (CDC), moreover, faces steep budget reductions, despite added resources to fight the opioid crisis.

	In addition, the administration proposes to realize significant “savings” from Medicare and Medicaid, with a particular focus on reducing outlays for prescription drugs.  One proposal calls for Medicare Part D plans to return a portion of drug company rebates to beneficiaries starting in 2019, a move strongly opposed by pharmacy benefit managers (PBMs) but applauded by pharma companies. There are further changes to catastrophic coverage of drugs for Medicare beneficiaries, and to reimbursement for drugs covered by Medicare Part B. Most interesting is an administration proposal for a demonstration that authorizes up to five state Medicaid programs to test methods for negotiating prices directly with manufacturers, utilizing closed formularies and gaining an exemption from best price reporting under the Medicaid drug rebate program.

	Similar changes in Medicare drug benefits are authorized in a broad budget bill approved by Congress and signed into law by the President just before unveiling the 2019 budget plan. The measure extends government funding through March 23 to prevent another government shutdown, providing Congress once again with more time to hash out an appropriation deal for the current year.

	The bill hits pharma companies hard by making a significant increase in the portion industry pays for coverage of drugs in the Part D coverage gap, or “donut hole.” Avalere Health estimated that the measure could have a “multi-billion-dollar impact on some large companies,” boosting manufacturer costs significantly, but without making any real significant reduction to beneficiary spending. The main winners are health plans, which will see costs decline over time, as will the federal government.

	The new budget law also revises reimbursement for biosimilars in the coverage gap, kills the Independent Payment Advisory Board, and updates provisions of the Medicaid drug rebate program. It won bipartisan support on Capitol Hill by extending the Children’s Health Insurance Program through 2027 and for increasing funds to combat the opioid crisis. 

The Trump budget boosts funding for FDA but squeezes resources for NIH and healthcare.