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US manufacturers focus on preparing capacity while vaccines and treatments for COVID-19 are being developed and tested.
US bio/pharmaceutical manufacturers are working urgently to not only develop vaccines and treatments for COVID-19 but to ensure that the manufacturing capacity to produce them is available once they are approved. Preparing capacity before a drug is even in clinical trials is a significant departure from standard practice and carries the risk of investing capital in equipment and facilities for a drug that might not become commercial, but the pressing need for treatments and vaccines for the novel coronavirus is driving new ways of planning for manufacturing capacity.
The US government is taking on some of this financial risk through “Operation Warp Speed (OWS),” which is a public-private partnership to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics, the Department of Health and Human Services (HHS) said in a May 15, 2020 announcement that named leaders and advisors for the effort. The US government program will provide funding, and in return, companies will be expected to donate a portion of the product that is developed.
Approximately eight vaccine candidates are expected to be chosen to go through early-stage small clinical trials, and three to five candidates will proceed to larger-scale trials. HHS said that in the OWS vaccine development plan, “the manufacturing capacity developed will be used, to the extent practicable, for whatever vaccine is eventually successful, regardless of which firms have developed the capacity.” The government is also making plans for the infrastructure for packaging and distributing an eventual vaccine, including cold-chain storage and a supply of glass vials.
Biopharmaceutical companies are rushing to create capacity for COVID-19 vaccines both internally and through partnerships with contract development and manufacturing organizations (CDMOs). The past few weeks have brought multiple announcements of partnerships and scale-up plans.
Moderna announced on Monday, May 18, 2020 positive interim Phase I data from its clinical trial of its mRNA vaccine candidate (mRNA-1273) against the novel coronavirus, which had received a Fast Track designation from FDA on May 12. The company continues to move as quickly as possible through testing and is concurrently investing to scale up manufacturing at its facilities and at facilities at its contract development and manufacturing (CDMO) partner, Lonza. Funding from HHS’ Biomedical Advanced Research and Development Authority (BARDA) supported trial planning and will support trial execution as well as manufacturing scaleup, Moderna noted in the press release.
Pfizer, which is co-developing an mRNA vaccine with BioNTech SE, is gearing up for potential production at three US facilities: St. Louis, MO for critical raw material manufacturing; Andover, MA for drug substance manufacturing; and Kalamazoo, MI for formulation and fill, the company said in a May 5, 2020 release. Preparations include ordering materials, planning for two parallel supply chains, modifying facilities for the vaccine candidates and reprioritizing capacity, and hiring and training staff. Production could also occur at its site in Puurs, Belgium, and more sites could be selected. BioNTech is manufacturing vaccines for the clinical trials at its GMP-certified mRNA manufacturing facilities in Mainz and Idar-Oberstein, Germany, and plans to increase capacity further. Participants in initial clinical trials were dosed in Germany and the US, the companies said on May 5.
Johnson & Johnson announced manufacturing agreements with Emergent BioSolutions and then with Catalent at the end of April 2020 for J&J’s lead investigational vaccine candidate for COVID-19. The vaccine will be developed and manufactured using the AdVac viral vector technology and PER.C6 cell line from the Janssen Pharmaceutical Companies of Johnson & Johnson, which the company says allows rapid manufacturing scale-up. J&J said in an April 23, 2020 press release that it was preparing for clinical vaccine production at its Netherlands facility for initiating Phase 1 human clinical studies of its vaccine candidate in September 2020, and that it was planning to increase capacity globally to be able to supply more than one billion doses. Catalent said in an April 29, 2020 press release that its Biologics business unit would prepare for large-scale commercial manufacturing at its facility in Bloomington, IN. The company said it planned to hire approximately 300 additional employees at the site for this program starting in July 2020 to meet operational readiness and 24×7 manufacturing schedules by January 2021. And on May 14, 2020, CDMO Vibalogics, which specializes in virotherapy products and has a GMP-manufacturing facility in Cuxhaven, Germany, said that it had been contracted to manufacture multiple batches of Janssen’s vaccine for clinical trials.
Novavax is moving forward with clinical development of its COVID-19 vaccine candidate, with funding by the Coalition for Epidemic Preparedness Innovations (CEPI) (a consortium created in 2017 with funding from multiple countries and the Bill and Melinda Gates Foundation) that will be used for clinical trials, process development, and manufacturing. In a May 11, 2020 press release, CEPI noted the importance of investing now in manufacturing, even while vaccines are still in development.
CEPI has also funded Inovio’s investigational DNA vaccine (INO-4800). Inovio announced on April 30, 2020 that it was expanding its manufacturing partnership with German CMO Richter-Helm BioLogics to support large-scale manufacturing of DNA plasmids. Inovio’s vaccine is in Phase 1 clinical testing in the US, and the company plans to manufacture one million doses by the end of 2020.
Catalent is also manufacturing the drug substance for human clinical trials and potential commercial manufacture of Arcturus Therapeutics’ COVID-19 mRNA vaccine candidate (LUNAR-COV19), Catalent announced on May 4, 2020.
UK-based AstraZeneca and the University of Oxford announced a development and manufacturing partnership on April 30, 2020. AstraZeneca will manufacture the recombinant adenovirus vaccine (ChAdOx1) developed by the University of Oxford’s Jenner Institute and Oxford Vaccine Group. According to a May 18, 2020 article in Fortune, AstraZeneca will make 30 million doses for the UK by September and 100 million doses by the end of 2020.
Packaging and aseptic filling capacity are also crucial for vaccine manufacture. Injectable vaccines are traditionally packaged in glass vials, and a supply of vials is crucial. The possibility of using polymeric prefilled syringes that could be made using the blow-fill-seal (BFS) process, which produces the containers and fills them in one step, is being considered. On March 18, 2020, HHS announced the launch of a new public-private partnership for Rapid Aseptic Packaging of Injectable Drugs (RAPID) to investigate the possibility of using BFS for vaccines in prefilled syringes and to build a network of facilities that could be called upon as surge capacity for fill/finish operations. According to HHS, BFS is used for sterile medicines, including oral rotavirus vaccines. RAPID is being led by ApiJect Systems America, a public benefit corporation based in Stamford, CT. On May 12, 2020, ApiJect announced that it had been awarded an HHS-DOD contract to accelerate the project. RAPID USA’s Project Jumpstart will stockpile needle hubs for the prefilled syringes and contract with BFS facilities to prepare capacity to enable production before the end of 2020, with the capability to manufacture a minimum of 30 million prefilled syringes per month. Additional networks of facilities are being planned for 2021.
In addition to preparing for rapid vaccine scale-up, manufacturers are expanding production of therapeutics that are being tested as treatments for patients with COVID-19. Gilead Sciences’ investigational antiviral remdesivir received emergency use authorization from FDA for the treatment of COVID-19 on May 1, 2020, and the company planned to rapidly scale-up production. Gilead said it would also increase capacity by working with manufacturing partners. A partnership with Mylan, for example, was announced on May 12, 2020.
Multiple suppliers have also been ramping up capacity for hydroxychloroquine (HCQ) and related products that are being used as investigational treatments for COVID-19. In late March, Bayer, Novartis, Mylan, and Teva announced donations and ramp-up of supply. CDMO AMRI said on April 30, 2020, that it was increasing capacity for HCQ API at its Rensselaer, NY, manufacturing facility. On May 11, 2020, UK-based CDMO Sterling Pharma Solutions announced that it would manufacture HCQ API and had entered a partnership with Durham, NC-based Accord Healthcare to manufacture the finished drug product.
CytoDyn’s leronlimab, a novel CCR5 antagonist with the potential for multiple therapeutic indications, received an emergency investigational new drug (EIND) authorization from FDA and is in clinical trials. On May 5, 2020, CDMO Ajinomoto Bio-Pharma Services announced that it would manufacture the drug for the trials.
As manufacturers consider how to rapidly scale up capacity for drugs to combat the global pandemic, new technologies for facility and process design and new ways of planning and executing facility construction may play a role. In addition-at least until a successful vaccine is widely available-companies need to consider how to keep their manufacturing workforce healthy by using engineering controls and new work practices. On Tuesday, May 26, the Pharmaceutical Technology and BioPharm International editors will host a webcast with facility design experts to discuss these topics. Register at this link for the “Editors’ Series: Strategies for Designing Adaptable, Resilient Bio/Pharma Facilities.”