The US Department of Health and Human Services (HHS) should apply learnings from failures at its drug-manufacturing centers during COVID-19 as it transitions to a new program, concludes a Government Accountability Office (GAO) report published yesterday.
HHS, the primary federal department responsible for public health preparedness, created the Centers for Innovation in Advanced Development and Manufacturing (CIADM) in 2012 to improve domestic infrastructure and expertise to make medical countermeasures (eg, drugs, vaccines) in response to public health emergencies, the report authors noted.
CIADM was developed in response to concerns raised during the 2009 the H1N1 flu pandemic about the United States' ability to rapidly manufacture countermeasures in an emergency. The federal government acknowledged that it was unable to provide enough vaccines before the pandemic spread through the population.
As a result, HHS awarded funding to three contractors (two biomanufacturing companies and one university) to scale up production to make 50 million finished doses within 4 months of a flu pandemic, provide services such as production of drug substances for clinical trials, and train a workforce to carry out these duties.
Lack of incentives for large drug companies
Funded by the federal Coronavirus Aid, Relief, and Economic Security (CARES) Act, the GAO monitors the work of federal agencies relating to the pandemic. As part of this work, the GAO reviewed HHS documents and correspondence and interviewed officials at CIADM sites from January 2022 to February 2023.
In the report's introductory letter to Congressional committees, the GAO said that it had previously reported that, like pharmaceutical production in general, manufacturing countermeasures is complex, time-consuming, and expensive.
"Unlike most pharmaceutical products, there is no general commercial market for countermeasures used in response to low-probability, high-consequence events," the report said. "This may reduce incentives for large pharmaceutical companies to invest consistently in these products instead of others that may be more profitable."
Detailed plans still in development
Before the pandemic, HHS funded the sites to provide small batches of drug substances to other manufacturers. After the pandemic began, HHS increased funding to reserve capacity to make COVID-19 vaccines formulated under the Operation Warp Speed initiative on a larger scale.
Unlike most pharmaceutical products, there is no general commercial market for countermeasures used in response to low-probability, high-consequence events.
But CIADM had difficulty reliably producing larger product amounts, resulting in deficiencies such as poor quality control that led to the shuttering of one site, Emergent BioSolutions, due to cross-contamination. As a result, the troubled site had to discard nearly 400 million COVID-19 vaccine doses in late 2020 and early 2021.
An HHS review identified a lack of regular manufacturing work both internally and from other manufacturers, caused in part by insufficient dedicated funding and trouble attracting external manufacturers to use the site to produce countermeasures.
HHS is now sunsetting CIADM and is in the early development of a new model, the National Biopharmaceutical Manufacturing Partnership (BioMaP), but the GAO said it's unclear how the new program will address the problems CIADM faced during the pandemic.
For example, HHS intends to use a different contracting structure in BioMaP to incentivize the participation of industry partners. However, this different structure requires additional expertise to manage effectively. "Moreover, HHS told GAO that its contracting staff had previously faced resource challenges using this different contracting structure for other programs during the COVID-19 pandemic," the report said.
In April 2022, HHS officials told the GAO that it had only half the contracting staff needed to manage its portfolio, which could run the risk of not having the resources and expertise to effectively manage BioMaP.
Also, "HHS does not have a sustainable source of funding for the new program model, and it has not yet developed detailed plans or budgets. HHS officials said that, without sustained funding for BioMaP or a similar program, the agency would be unprepared to respond to the next pandemic."
Contracting structure management
The report recommends that the HHS secretary direct the Biomedical Advanced Research and Development Authority (BARDA), an HHS department, to incorporate into its new program a way to systematically evaluate and respond to past challenges and future risks tied to advanced countermeasure development and the manufacturing of countermeasures.
HHS officials said that, without sustained funding for BioMaP or a similar program, the agency would be unprepared to respond to the next pandemic.
Specifically, it said, BARDA should address "challenges related to funding and risks associated with effectively managing the contracting structure," the GAO said. "Such an approach should clearly document program risks, ensure that progress in addressing risks is tracked, estimate needed program resources, and communicate this information to key decision makers."
The GAO said that HHS concurred with the report's recommendations.