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Action needed to prevent manufacturing bottlenecks on COVID-19 therapies

Urgent steps needed to prioritize, expand manufacturing capacity for most promising therapies

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Demand for COVID-19 therapies could far exceed supplies unless urgent steps are taken to prioritize and expand manufacturing capacity for the most promising therapeutic candidates, according to biopharma industry executives and public policy scholars.

A survey of BIO members conducted by the Boston Consulting Group (BCG) has identified bottlenecks that, if not addressed quickly, could limit supplies of drugs, and in particular biologics, to treat COVID-19.

Positive results from trials of immune modulators and mAbs that have already started or that will start soon could fuel demand that exceeds manufacturing capacity, said Mark McClellan, director of the Duke-Margolis Center for Health Policy, during a webinar on Monday sponsored by the center. McClellan serves on the boards of Johnson & Johnson (NYSE:JNJ) and Cigna Corp. (NYSE:CI).

In the absence of a vaccine, the potential demand for therapies over the next six months could include 130,000 Americans who are expected to be hospitalized with COVID-19 and 2.4 million non-hospitalized symptomatic COVID-19 patients, McClellan said. In addition, therapies, especially those with prophylactic potential, might be required for 10.2 million close contacts of patients, as well as millions of healthcare workers.

“There simply is not enough capacity.”

Frances Zipp, Lachman Consultants

Demand will continue even after vaccines are authorized or approved, given the expected delays in producing and distributing vaccines globally and the fact that those vaccines are not likely to be 100% effective.

Prioritization of production is especially important because it won’t be possible to manufacture every potential therapy in quantities large enough to meet demand, Frances Zipp, president and CEO of Lachman Consultants, said in the webinar. “There will be products that will not be able to be manufactured. There simply is not enough capacity.”

McClellan raised the prospect of a “command approach by the government, using or threatening use of the Defense Production Act, to reallocate production” in the fall if manufacturing bottlenecks create shortages of potentially life-saving COVID-19 therapeutics.

He also noted that last-minute measures won’t solve the problem because manufacturing many kinds of therapies, especially biologics, can’t be cranked up quickly.

Mapping mAb demand

A report released by the Duke Margolis center noted that the gap between manufacturing capacity and likely demand is particularly large for mAbs, and suggested that to maximize mAb access, the U.S. government could become actively involved, as it has with vaccine production.

If mAbs are found to be safe and effective, the report estimates demand in the U.S. over a year at 260,000 doses for hospitalized patients, 4.8 million doses for non-hospitalized symptomatic patients, and over 20 million doses for people with close exposure to confirmed cases. The demand estimates are conservative, based on assumptions of a single mAb dose per patient and current estimates of COVID-19 prevalence.

The report concludes, however, that industry is on track to meet only the needs of hospitalized patients.

Unlike at-risk vaccine production which is being funded by the U.S. government, COVID-19 therapeutics developers “are largely making their own arrangements for sufficient manufacturing capacity,” and most mAb developers are producing their own products rather than relying on contract manufacturers, the report noted.

“In the near term capacity is fixed.”

Patti Seymour, BDO USA

Citing data from BDO USA LLP’s bioTRAK database, Duke Margolis reported that 78% of mAb production in the U.S. is controlled by manufacturers that make their own products.

And while the time required to create new mAb manufacturing capacity has been reduced substantially in recent years, it takes at least 18 months to set up a modular production facility.

Furthermore, the reported stated that it may be challenging for mAb manufacturers to make large enough investments to meet demand, especially if the pandemic worsens in the fall, and competition for manufacturing capacity “may create complications in matching limited available supply with the particular mAbs that demonstrate clinical effectiveness.”

To mitigate these challenges, Duke Margolis suggested that the U.S. government could step in to coordinate and facilitate manufacturing of COVID-19 therapeutics; activities could include “assistance with anticipating issues in technology transfer and contractual arrangements among manufacturers, as well as provision of some financial support to provide additional manufacturing capacity if shortages are expected.”

Reallocation of capacity may be the only way to quickly expand mAb supplies, Patti Seymour, managing director at BDO, said in the webinar.

“In the near term capacity is fixed,” Seymour said. “Even with single use bioreactors it takes months and months, if not years, assuming all the equipment needed to put up the facility is available” to bring new capacity online.

In addition, there are shortages of workers with the necessary skills. “Industry is already under resourced in terms of having the skill sets to work in these facilities,” she said.

Identifying bottlenecks

Speaking at the Duke Margolis webinar, BIO CEO Michelle McMurry-Heath presented results of the first phase of BCG’s survey of executives from about 20 BIO member companies of various sizes developing COVID-19 therapies across a range of modalities.

The highest priority bottlenecks identified were biologics drug substance production, sterile fill/finish capacity and lyophilization capacity.

BCG’s interviews identified the need for an “accelerated technology transfer review process and faster site registrations to expand available capacity,” according to a summary slide.

Biopharma executives also called for international regulatory harmonization, including, for example, the possibility of rapid global roll-outs of products following FDA approvals, Philip Berk, managing director and senior partner at BCG, said in the webinar.

The executives also discussed the need to address trade restrictions, including export controls, that could reduce production of therapies by limiting access to raw materials, or create shortages by restricting exports of finished therapies, Berk reported.

Responses to the need for manufacturing capacity should take into consideration the probability that therapies will come online in phases, Phyllis Arthur, BIO’s VP for infectious diseases and diagnostics policy, said in the webinar. The first cohort of authorizations or approvals won’t necessarily be the most effective therapies, she said, so it is important to ensure there is capacity for products that could be introduced later.

In the medium term, the U.S. government could create incentives that would expand manufacturing capacity for COVID-19 and future outbreaks, Arthur said. She highlighted opportunities to provide tax incentives for the purchase of equipment, for building manufacturing plants, and for training workers with the skills required to manufacture biologics and other modalities.

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