The U.S. Department of Commerce wants to know the current condition of the U.S.’ public health industrial base and would like recommendations on how best to strengthen it to ensure resilient domestic supply chains for essential medicines, medical countermeasures (MCMs) and critical inputs deemed necessary to protect against emerging infectious diseases and chemical, biological, radiological and nuclear events.
Comments received by Dec. 23 will be used to inform a report the department must submit to the White House, in accordance with an executive order President Donald Trump issued in August aimed at bringing more drug- and device-related manufacturing back to the U.S.
Although there will be a different president in the White House Feb. 2 when the report is due, U.S. reliance on other countries for essential medical products has become a bipartisan national security issue in Congress amid shortages of supplies during the COVID-19 pandemic.
The public health industrial base, as defined by the executive order, consists of all the facilities and workforce in the U.S. involved in the R&D, manufacturing and supply chains related to essential drugs, MCMs and critical inputs.
For devices and medical equipment, “critical inputs” are components that, if replaced by an equivalent alternative, would require an amendment to the final product’s 510(k). For drugs, those inputs include drug finishing, active pharmaceutical ingredients (APIs) and the key starting materials to produce the APIs. For blood products and products derived from animals, the industrial base consists of all aspects of the extraction, processing and formulation supply chain.
In its request for public comment, to be published in the Dec. 2 Federal Register, Commerce is seeking answers to 17 specific questions, some of which are only relevant to current participants in the U.S. public health industrial base. For instance, one question asks whether foreign dependencies exist in any part of the commenter’s supply chain for critical inputs or finished products. Another question addresses the threat of cybercrime or malicious cyber activity to commenters and members of their supply chain.
Comments should be submitted to docket number BIS–2020–0034 on www.regulations.gov.
HIV trial networks streamlined
The NIH’s National Institute of Allergy and Infectious Diseases restructured its HIV clinical trials network to reduce administrative and oversight costs, allowing more funds to be allocated to trials to advance key areas of research.
Under the new streamlined structure, one network will work on developing a durable HIV vaccine; a second one will work to advance nonvaccine HIV prevention products and strategies to meet the needs of diverse populations worldwide. The other two networks will develop and evaluate potential new treatments and cures for HIV and HIV-related complications and co-infections, with one focusing on adults and the other on infants, children, adolescents, and pregnant and postpartum women.
The streamlining also gives the networks the flexibility to leverage their infrastructure to rapidly respond to emerging infectious diseases, such as COVID-19, the NIH said. The networks are intended to lead HIV research for the next seven years. The NIH said it intends to provide about $375 million to support the networks in the first year.
Grants to advance use of RWD, RWE
The FDA took another step this week in exploring the use of real-world data (RWD) to generate real-world evidence (RWE) to support drug approvals and post-approval requirements.
The agency announced four new grants Dec. 1 that are intended to further the science on RWD and RWE. One award went to researchers at Brigham and Women’s Hospital and Harvard Medical School, who will study the benefits of linking randomized clinical trials (RCTs) with RWD by extending patients’ follow-up time beyond trial completion, capturing additional effectiveness and safety outcomes, minimizing missing data and generalizing trial results to real-world target populations.
Linking RCTs with RWD also is expected to improve understanding about potential discrepancies between RCTs and nonrandomized studies, the FDA said.
The second grant went to researchers at the University of North Carolina and Genentech Inc., who plan to apply novel statistical approaches to develop a decision framework for hybrid RCT designs that combine internal control arms with patient data from RWD sources.
The third grant, to researchers at the Critical Path Institute and Tufts Medical Center, will support a neonatal pilot project aimed at advancing standards and methodologies to generate RWE from RWD. Collecting data from neonatal intensive care units worldwide and then depositing it in a RWD and analytics platform, the project is expected to facilitate the future design and conduct of neonatal trials.
The final grant will fund a three-year program, to be led by researchers at Verantos Inc., comparing traditional RWE approaches with more advanced approaches to increase confidence in implementing RWE within regulatory and clinical pathways.
GAO, National Academies, report on AI in health care
The U.S. Government Accountability Office (GAO) and the National Academy of Medicine posted a technology assessment for the use of artificial intelligence (AI) in health care, highlighting the opportunities for AI to relieve the pressure on the U.S. health care system.
The report delves into the opportunities presented by both clinical and administrative AI tools, neither of which has been widely adopted by hospitals and physician practices. Among the impediments to more widespread use of AI is the problem of data bias and privacy, but the report also notes that liability is fraught with uncertainty due to the various parties involved in the development and deployment of AI tools.
One of the key uncertainties in the space is how the FDA will regulate AI algorithms. That lack of regulatory certainty is cited as another source of concern about product liability litigation that could blunt uptake. Policies published by the International Medical Device Regulators Forum were seen as a possible solution to the regulatory oversight question.
Developers also indicated that one of the impediments to the use of AI is the difficulty in accessing high-quality datasets for the development and validation of an algorithm. One possible solution would be for the U.S. government to establish a data commons that would provide the required datasets.
ICER not sold on roxadustat
The Institute for Clinical and Economic Review (ICER) released a draft evidence report Nov. 30 assessing the comparative clinical effectiveness and value of roxadustat to treat anemia in chronic kidney disease (CKD).
“Although it has been suggested to be a safer alternative to ESAs [erythropoiesis-stimulating agents], the evidence does not currently support that conclusion,” according to the interim report, which found insufficient evidence to compare the two treatments.
On the plus side, roxadustat provides an oral option for treating anemia in CKD and reduces the need for I.V. iron. But cost-effectiveness will depend on the manufacturer’s price, ICER said.
A first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the U.S. market by Fibrogen Inc. and Astrazeneca plc, roxadustat is under review by the FDA with a PDUFA date later this month.
Comments on ICER’s draft report are due by Jan. 5. A virtual public meeting on the evidence report is scheduled for Feb. 11.
Teva, Cephalon latest EC targets
The European Commission fined Teva Pharmaceutical Industries Ltd. and Cephalon more than $73 million for a pay-for-delay settlement the companies reached in 2005 – six years before Cephalon became a Teva subsidiary.
Under the settlement, Teva agreed to withdraw its Provigil (modafinil) generic, which was marketed briefly in 2005 in the U.K. at half the price of Provigil, and to delay the European market entry of the generic until 2012, even though the main European patents for Cephalon’s sleep disorder drug expired in 2005.
The settlement included cash payments and a package of commercial side-deals beneficial to Teva, such as a distribution agreement, purchases of raw materials from Teva, and Cephalon’s grant of access to clinical data that was highly valuable to Teva for a different medicine, according to the EC.
The commission said its action against Teva and Cephalon completes the cycle of pay-for-delay investigations launched with its 2009 pharmaceutical sector inquiry.
To date, the EC has fined brand and generic companies in three other pay-for-delay investigations, involving Servier SA’s blood pressure drug perindopril, H. Lundbeck A/S’ blockbuster antidepressant citalopram and Johnson & Johnson’s fentanyl depot patch used to treat pain.
Hungary looks to Russian vaccine
Russia and Hungary are in talks for how best to provide Russia’s COVID-19 vaccine to Hungary.
During negotiations last week, it was decided that Hungarian specialists would visit Russia to study its vaccine production with an eye on localizing part of the production in Hungary, according to Russia’s Ministry of Health.
However, Hungarian Foreign Minister Peter Siyjarto said the question of where a vaccine is produced is of secondary importance. The top priority is getting a high-quality COVID-19 vaccine, he added.