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Jill Wechsler is Pharm Exec's Washington Corespondent
Biopharma companies have been working overtime to supply billions of doses of any safe and effective preventive. But the tight timeframe means they can't wait for final clinical test results to begin preparing large-scale manufacturing operations and to address critical supply chain issues.
As the Trump administration revs up its Operation Warp Speed initiative to provide new COVID-19 vaccines and therapeutics for patients, biopharmaceutical companies and federal agencies have been working overtime and assuming considerable risk to be able to supply billions of doses of any safe and effective preventive. With research underway for more than 175 vaccine candidates across a wide range of technologies, experts expect to identify several promising vaccines in the coming months. The aim is to have “multiple shots on goal,” along with multiple goals to shoot at, the experts quip. But the tight timeframe means that companies cannot wait for final clinical test results to begin preparing large-scale manufacturing operations and to address supply chain issues critical for delivering preventives globally.
Consequently, manufacturers and funding agencies will “have to proceed at risk,” acknowledges Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID). Instead of spending several years testing vaccine candidates and then ramping up production based on successful findings, industry and government agencies have to invest in things and build things “that we may never use,” he said in a webinar sponsored by the Duke Margolis Center for Health Policy May 13, 2020. It means launching production as sponsors transition from phase 1 studies, even though such investment may well exceed $1 billion or more, he noted.
To move to full scale production, manufacturers have to assess which vaccine manufacturing sites can switch to a new product and where a company can reduce current production of a vaccine with less demand, explained former FDA and National Security Council official Luciana Borio, now at In-Q-Tel. The development of a range of vaccine platforms – inactivated, non-replicating, live attenuated, protein, RNA – will require a similar variety in manufacturing capacity and create added challenges for scale-up. And if a COVID-19 vaccine emerges this fall, that would coincide with the annual seasonal flu vaccination campaign, making it difficult for companies to pull away from production in that area, noted former FDA commissioner Scott Gottlieb.
A related problem is shortages in glass vials and needles needed for expanded fill-finish operations, said Adrian Hill of the Jenner Institute and Oxford Martin Programme on Vaccines in the United Kingdom, and that companies often “can’t just stop manufacturing other vaccines.” Paul Stoffels of Johnson & Johnson’s Janssen Pharmaceuticals similarly considers “fill and finish critical,” noting that it’s impossible to plan to produce 300,000 vaccines without vials and finishing operations.
While manufacturers and funding agencies aim to support “equitable distribution” of any successful vaccines to all regions, Gottlieb believes it is “inevitable” that countries developing and producing a successful preventive will first provide it to its own population. That speaks to importance of multiple vaccine platforms and large scale manufacturing in many regions. The UK vaccine program is working with manufacturers in India and China with extensive vaccine production capacity, while the Coalition for Epidemic Preparedness Innovation (CEPI) is supporting several programs to develop vaccines for global distribution.
Given the many challenges in manufacturing any one vaccine, Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), agreed that multiple vaccines will need to be approved to meet global demand. As more vaccines move into clinical testing, FDA is working overtime to provide the best regulatory advice it can, and very quickly, he commented. Marks said that FDA is “willing to take certain calculated risks to get into phase 1,” and will accept novel trial designs, particularly with vaccine platforms that have been used before. But preclinical testing still will have to be done, as FDA has to convince people that we’re “not taking shortcuts here.”
Fauci emphasized the importance of coordinating clinical trials for the many different vaccine candidates and the need for consistent protocols to gain definitive answers about whether a candidate works or not. Without complete clinical trials, he worries that researchers may get a signal that “strongly indicates” a response, but “doesn’t nail it down.” He recommends that sponsors utilize clinical research networks in locations with high incidences of COVID cases to facilitate obtaining clear results. Marks similarly advised sponsors to “go where the cases are – not the traditional sites,” acknowledging that widespread infection rates, ironically, should facilitate getting needed answers. And while sponsors should “space out” trials to different locations to avoid bias, study endpoints should be similar enough to be able to compare results from different trials.
While the medical community reports that many patients are recovering from COVID by mounting a strong immune response to the virus, Marks acknowledges that scientists still have only a limited understanding of what will constitute long-term, definitive protection. This vaccine expert admits to having “great concerns” about a second pandemic wave this fall and winter and hopes to have some viable treatment by then. He’d be very pleased with a vaccine with strong efficacy data, and one that could get to herd immunity “would be really nice,” he commented. But regulators and researchers will take any preventive that indicates it can help get the pandemic under control, even, at this point, with only limited assurances for long-term success.
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