How have lessons from the pandemic influenced the way companies use technology to perform quality-control procedures?

A New View on Quality Control?

Preclinical and clinical research is improving ADC development.

ADC Development Improves on Research

Strategizing drug development in the preclinical phase has merit.

Preclinical Strategies Benefit Biopharma Development

Perfusion cell culture gains advantage with PAT tools advancement.

Perfusion Cell Culture is Gaining Momentum

Coating is an alternative to silicone oil as a lubricant. URL for article 

Syringe Coating Technology

Redefining Contamination Control for CGTs

Novavax COVID-19 Vaccine Receives EUA in Indonesia

FDA Grants EUA for Pfizer-BioNTech COVID-19 Vaccine Use in Children

FDA has published its review of the accomplishments the agency achieved in 2021. 

FDA 2021 Year in Review–Working for You 

details the agency’s response to COVID-19, including vaccine, treatment, and testing authorizations. FDA has also been monitoring variants of the virus and issuing guidance and contingency plans for dealing with the pandemic. The report also discusses the agency’s efforts for addressing the misuse of prescription drugs, the problem of fraudulent medicines, and the advancement of generic drugs and biosimilars, as well as its work in food safety and tobacco products.

“While much of the attention the agency received in 2021 focused on our response to the pandemic, I am pleased to note that, despite a great deal of uncertainty, the agency was able to accomplish a wide range of its priorities that are already protecting the health and well-being of millions of people living in the US,” said Acting Commissioner Janet Woodcock, MD, in the report. “Every year the FDA reviews hundreds of product applications, ultimately determining which drugs, devices, or biological products (e.g., vaccines) will be marketed in the US. The process involved is rigorous, thoughtful and always adheres to standards for safety and effectiveness. We help to ensure that the human and animal food supply is safe, sanitary, and accurately labeled, and that cosmetic products are safe and properly labeled,” said Woodcock.

Articles

The agency discusses its response to COVID-19 and other milestones in its year-end review.

FDA Publishes 2021 Year in Review

On January 18, 2022, the European Medicines Agency (EMA) stated that its COVID-19 task force reviewed several studies involving approximately 65,000 pregnancies and did not find any sign of increased risk of complications, miscarriages, preterm births, or adverse events after vaccination with mRNA vaccines. “Despite some limitations in the data, the results appear consistent across studies looking at these outcomes,” the agency stated in a 

According to EMA, the studies also showed the vaccines reduce the risk of hospitalization and death in pregnant people as well as non-pregnant people, and side effects related to the mRNA vaccines in pregnant people matched those of non-pregnant people. “Given that so far pregnancy has been associated with a higher risk of severe COVID-19 particularly in the second and third trimesters, people who are pregnant or might become pregnant in the near future are encouraged to get vaccinated in line with national recommendations,” EMA stated in the release.

Because clinical trials do not usually include pregnant people, according to EMA, data on the use of the vaccines are obtained after authorization. The agency will review the latest data on these vaccines administered during pregnancy and will update product information as necessary. “In line with the EU’s safety monitoring plan for COVID-19 vaccines, those vaccines are closely monitored, and relevant new information emerging is continuously collected and promptly reviewed. Although very large numbers of people have already received COVID-19 vaccines, certain side effects may still emerge as more and more people are included in vaccination programmes. EMA’s safety committee, 

 will continue to monitor safety in pregnancy,” the agency stated.

The agency’s COVID-19 task force says latest data shows use of COVID-19 mRNA vaccines during pregnancy is safe.

COVID-19 Vaccines Safe for Use During Pregnancy, EMA States

Samsung Biologics announced on Jan. 12, 2022 that it plans to start building a new facility (designated Plant 5) at Songdo in Incheon, South Korea, this year. The facility will offer manufacturing for multi-modal products, including cell and gene therapies and next-generation vaccines that utilize messenger RNA (mRNA), plasmid DNA, and viral vectors. The expansion is part of the company’s 2022 growth plan.

The new facility will be an addition to the mRNA vaccine drug substance (DS) manufacturing suite that the company is currently adding to its existing facility in Songdo. The mRNA vaccine DS facility is expected to be ready for current good manufacturing practice operations within the earlier part of this year, according to a company press release.

Samsung Biologics is further looking to secure additional sites within Songdo for the future construction of another additional facility (designated Plant 6) and an open innovation center. In addition, the company is looking for overseas sites in multiple locations to maximize both its manufacturing capacity for producing large-scale biologics and to be in close proximity to global clients.

Samsung Biologics’ Plant 4 is currently under construction and is expected to be partially operational by the end of this year. When Plant 4 is fully completed in 2023, the company expects to have a total capacity of 620,000 L.

“Through proactive investment in increasing our manufacturing capacity, enhancing portfolio diversification, and expanding facilities in overseas, Samsung Biologics will be able to accelerate the build-up of its core success drivers as the next growth engine of the industry,” said John Rim, CEO of Samsung Biologics, in a company press release.

Samsung Biologics is planning to construct a new manufacturing facility in Incheon, South Korea, that will offer multi-product manufacturing, including cell and gene therapies and next-gen vaccines.

Samsung Biologics to Construct New Manufacturing Facility for Next-Gen Vaccines and CGT

Following their July 2021 merger, Protagen Protein Services, BioAnalytix, and GeneWerk announced on Jan. 12, 2022 that their unified operations and re-branded name is ProtaGene, a contract research organization for the biopharmaceutical and cell and gene therapy industries.

The three legacy companies' combined synergy provides advanced, integrated, and complete protein and gene analytic services for biological therapeutics and cell and gene therapy platforms. ProtaGene provides services from discovery to commercialization.

Previously, Protagen Protein Services and BioAnalytix merged in April 2019, and GeneWerk, which specializes in vector safety, integration site analysis, and bioinformatics, was combined with the group in 2021.

"We are very excited to launch ProtaGene. The track record and reputation of the three legacy entities are individually impressive, and their combination into a single, globally integrated business delivers significant compounded value for our sponsors," said Martin Blüggel, CEO of ProtaGene and the founder of Protagen Protein Services, in a company press release.

"By combining our capabilities, platforms and knowledge, we can now provide our US-based biopharmaceutical and gene therapy customers advanced access to the broadest analytical offering from discovery to market, from a single vendor relationship," said Kirtland Poss, CEO-US of ProtaGene and the founder of BioAnalytix, in the press release.

"Our unique experience in gene analytics—especially integration site analysis, vector purity, vector copy numbers, and bioinformatics analysis for preclinical development and clinical trials—will support many innovators in taking breakthrough therapies to the clinic," added Annette Deichmann, senior vice-president of Cell and Gene Therapy at ProtaGene and the co-founder of GeneWerk, in the press release.

After a previously announced merger, Protagen Protein Services, BioAnalytix, and GeneWerk have formed a new CRO under the name ProtaGene.

Protagen Protein Services, BioAnalytix, and GeneWerk Combine to Form New CRO, ProtaGene 

Forge Biologics, a gene-therapy focused contract development and manufacturing organization, announced plans to accelerate expansion plans for their manufacturing facility in Columbus, Ohio on Jan. 10, 2022. The $240 million expansion is set to increase the overall manufacturing footprint of the company to over 200,000 ft².

According to a company press release, the expansion will significantly increase the number and capacity of Forge’s bioreactors, including installation of 5000-L bioreactors for large-scale current good manufacturing practice (CGMP) client needs. The company expects these to be available for client use in the latter half of 2022.

The expansion will also include 20 CGMP manufacturing suites, with the ability to add more suites in the current facility in the future. Additional automated CGMP fill/finish capabilities, designed with a cleanroom background classifications that meet European Medicines Agency requirements for late-stage clinical and commercial filling needs, will be included as well.

“We are excited to deliver on our goal of offering our clients expanded manufacturing capacity, while providing access to some of the largest suspension bioreactors available in the industry,” said Timothy J. Miller, CEO, president, and co-founder of Forge, in the press release. “This increased scale, combined with our automated fill/finish capabilities, positions Forge as an ideal partner for clients moving beyond the clinic to commercial launch and supply, particularly those needing to manufacture CGMP [adeno-associated virus therapies.]”

Forge Biologics secured the funding for the accelerated expansion through an $80 million secured financing agreement with MidCap Financial. The expansion, which was initially announced in 2021, had secured $160 million in funding prior to this agreement.

CDMO Forge Biologics will accelerate its manufacturing capacity expansion using an additional $80 million in funding it recently secured.

Forge Biologics to Expand Manufacturing Facility

Pfizer and Beam Therapeutics, a biotechnology company developing precision genetic medicines through base editing, announced an exclusive four-year research collaboration on Jan. 10, 2022. The collaboration, worth up to $1.35 billion, will use Beam’s 

 base editing programs to conduct research on three undisclosed targets for rare genetic diseases of the liver, muscle, and central nervous system.

The base editing program will leverage Beam’s proprietary

 delivery technologies, which use messenger RNA (mRNA) and lipid nanoparticles (LNP) to deliver base editors to target organs. These technologies are designed to enable precision genetic medicines that target a single base in the genome without making a double-stranded break in the DNA. According to a Pfizer press release, this would create an efficient edit when compared to traditional gene editing methods.

“At Pfizer, we believe in the powerful potential of mRNA and LNP technologies to address the greatest unmet needs for patients, as evidenced by the beneficial impact our mRNA/LNP-based COVID-19 vaccine is having on the pandemic,” said Mikael Dolsten, chief scientific officer and president, Worldwide Research, Development and Medical, Pfizer, in the press release. “We have a strong history in developing gene replacement therapies for rare diseases, and we see this collaboration with Beam as an opportunity to advance the next generation of gene editing therapies – an exciting scientific frontier – potentially leading to transformation for people living with rare genetic diseases.”

“We are thrilled to partner with Pfizer, a global leader in the design, development, and commercialization of novel medicines,” said John Evans, CEO of Beam, in the press release. “Our leading platform for precision genetic medicine has greatly evolved over the last few years, and we are committed to ensuring the broadest reach of these potentially life-changing technologies. This collaboration will provide a unique opportunity to create potentially transformative base editing programs for indications with critical unmet needs, leveraging our proprietary base editing technology and expanding delivery capabilities. We look forward to working together with Pfizer to advance these technologies and potentially expand our impact for people suffering from serious diseases.”

Pfizer will pay Beam $300 million upfront for their services in this collaboration. Should Pfizer exercise its opt-in license rights for all three targets, they will be eligible for development, regulatory, and commercial milestone payments for potential total deal consideration of up to $1.35 billion, in addition to royalties on global net sales.

Pfizer will pay Beam $300 million upfront to conduct research on three undisclosed base editing targets in the liver, muscle, and central nervous system.

Pfizer and Beam Enter Exclusive Multi-Target Research Collaboration

The Janssen Pharmaceutical Companies of Johnson & Johnson announced on Dec. 22, 2021, that the United Kingdom’s National Institute for Health and Care Excellence (NICE) has recommended Darzalex (daratumumab) in combination with Velcade (bortezomib), thalidomide and dexamethasone (DVTd), to treat adults with multiple myeloma, when an autologous stem cell transplant (ASCT) is suitable. Eligible patients in England and Wales will be able to access DVTd through the National Health Service (NHS).

According to a press release, NICE’s recommendation was based on “data from the Phase [III] CASSIOPEIA study (Part 1) with a median follow-up of 18.8 months which compared DVTd to standard of care (bortezomib, thalidomide and dexamethasone [VTd] alone) as induction and consolidation therapy in newly diagnosed multiple myeloma patients eligible for ASCT.”

“Multiple myeloma is a relapsing and remitting cancer, and while existing therapies can control it, these patients are in need of effective and well-tolerated treatment options that are given as early as possible in the treatment pathway to elicit a deep response and improve outcomes,” said Karthik Ramasamy, consultant haematologist at Oxford University Hospitals NHS Foundation Trust and lead clinician for Myeloma for the Thames Valley Cancer Network, in the press release. “A front-line treatment option such as daratumumab in combination with VTd will give clinicians an effective regimen to produce deeper and longer remissions for newly diagnosed myeloma patients compared to VTd alone.”

“We are delighted that people with multiple myeloma in England and Wales will now be able to access DVTd on the NHS,” said Amanda Cunnington, director of Health Economics, Market Access, Reimbursement and Health Affairs, Janssen-Cilag Limited, in the release. “[This] decision means access will now be equal across the UK and we’re proud to have worked collaboratively with stakeholders to achieve this outcome. Importantly, our work in multiple myeloma doesn’t stop here, and we remain committed to furthering advances in science and evolving innovation in blood cancers.”

The UK’s National Institute of Health and Care Excellence has recommended the use of Janssen’s Darzalex (daratumumab) in combination with Velcade (bortezomib), thalidomide and dexamethasone (DVTd) to treat adults with multiple myeloma.

NICE Recommends Darzalex in Combination with Velcade to Treat Multiple Myeloma

Shanghai Fosun Pharmaceutical (Fosun Pharma), a China-based healthcare group, and Insilico Medicine, a US-based artificial intelligence (AI)-driven drug discovery and development company, announced on Jan. 11, 2022 that they have entered into a collaboration agreement to advance the discovery and development of drugs targeting a number of different targets globally using AI technology.

The partnership includes an AI-driven drug discovery R&D collaboration on four biological targets as well as the co-development of Insilico’s glutaminyl-peptide cyclotransferase-like (QPCTL) program. Under the agreement, Insilico will receive a total upfront payment of $13 million for the four R&D collaboration projects and the co-development of the QPCTL program. Insilico will also receive potential milestone-based payments and share commercialization profits from the QPCTL program. Fosun Pharma will also make an equity investment in Insilico.

Through the collaboration, Insilico will combine its end-to-end AI-driven drug discovery platforms with Fosun Pharma’s clinical development and commercial expertise. Their goal is to discover and develop a portfolio of novel therapeutics. According to the agreement, Insilico will take responsibility for delivering a preclinical candidate for the QPCTL program and advancing it to the investigational new drug (IND) stage (via its R&D team). After that, Fosun Pharma will conduct human clinical studies and co-develop the candidate globally. Fosun Pharma’s R&D team will also nominate four therapeutic targets to be assessed by Insilico’s AI platform and R&D team in parallel programs.

In addition, as part of the collaboration, Fosun Pharma will gain access to Insilico’s PandaOmics and Chemistry42 platforms to advance its own internal AI-powered discovery and development efforts.

“We are pleased to enter into strategic collaboration with Insilico. Fosun Pharma is committed to promoting innovative R&D and is oriented towards fulfilling unmet clinical needs and improving products’ accessibility. We look forward to working with Insilico to leverage the technological and clinical development strengths of both companies, jointly improving the efficiency of innovative drug R&D and benefiting more patients worldwide," said Yifang Wu, chairman and CEO of Fosun Pharma, in a company press release.

“In partnering with Fosun Pharma, a leading pharmaceutical company, we begin a new era of AI-powered end-to-end drug discovery and development as human-machine collaboration becoming the new normal in precision drug discovery and development. We previously demonstrated that AI can be used to discover novel targets and generate novel molecules that can be tested in humans in record time. Now, we are partnering with one of the leading scientific teams in the pharmaceutical industry to take this technology to the next level for the benefit of patients worldwide,” said Alex Zhavoronkov, founder and CEO of Insilico Medicine, in the press release.

Fosun Pharma and Insilico Medicine will collaborate on AI-driven drug discovery and development of product candidates targeting multiple disease targets.

Fosun Pharma and Insilico Medicine Partner on Drug Discovery and Development Using Artificial Intelligence

Bristol Myers Squibb announced on Jan. 10, 2022 that it has entered into a research collaboration and license agreement with Century Therapeutics, a US-based biotechnology company, to develop and commercialize up to four induced pluripotent stem cell (iPSC)-derived, engineered natural killer cell (iNK) and/or T cell (iT) programs for hematologic malignancies and solid tumors.

The first two programs include one in acute myeloid leukemia (AML) and another in multiple myeloma. These programs could incorporate either the iNK or a gamma delta iT platform. Under the agreement, Bristol Myers Squibb has the option to add two additional programs, which can be nominated depending on certain conditions being met in the agreement.

Also under the agreement, Century will be responsible for development candidate discovery and preclinical development activities. Afterwards, Bristol Myers Squibb will be responsible for clinical development and commercialization activities subject to Century’s co-promotion rights on certain programs. Century will receive a $100 million upfront payment, and Bristol Myers Squibb will make a $50 million equity investment in Century’s common stock at $23.14 per share. Furthermore, Century will receive reimbursement of certain preclinical development costs for development candidates licensed by Bristol Myers Squibb. Century is also eligible for additional payments for future program initiations and development, regulatory, and commercial milestone payments totaling more than $3 billion across the four potential programs.

In addition, Century will also receive tiered royalties as a percentage of global net sales in the high-single to low-double digits. It may also elect to co-promote the AML program and one of the additional programs in the United States for no exercise fee. This latter would also trigger enhanced US royalties.

As part of this transaction with Bristol Myers Squibb, Century has amended its agreements with FUJIFILM Cellular Dynamics for Japanese development and commercialization rights for the products in these development programs.

“We are pleased to partner with Bristol Myers Squibb, a global leader in oncology and hematology, to further expand our pipeline of iPSC-derived cell therapy products for challenging hematological and solid tumor malignancies,” said Lalo Flores, CEO, Century Therapeutics, in a company press release. “Bristol Myers Squibb is an ideal partner for us because they bring extensive clinical development and scientific expertise in cell therapy that will increase the probability of technical success of these programs. Additionally, this collaboration will enable deployment of our next-generation iPSC platform to develop products targeting malignancies that are difficult for biotech companies to tackle on their own.”

“The collaboration with Century Therapeutics is an important part of our investment strategy in next-generation cell therapies for hematologic and solid tumors,” said Rupert Vessey, executive vice-president and president, Research & Early Development, Bristol Myers Squibb, in the press release. “Century’s iPSC-based gamma delta T and NK cell platforms show promise and are complementary to Bristol Myers Squibb’s existing cell therapy technologies. We look forward to exploring the full potential of the iPSC approach to develop potentially best-in-class allogeneic cell therapies to help patients with hematologic and solid tumor malignancies.”

The collaboration between Bristol Myers Squibb and Century Therapeutics will combine Century’s iPSC-derived allogeneic cell therapy platform with Bristol Myers Squibb’s expertise in cell therapy and oncology drug development.

Bristol Myers Squibb and Century Therapeutics to Collaborate on Developing iPSC-derived Allogeneic Cell Therapies

Fujifilm Diosynth Biotechnologies is expanding its BioProcess Innovation Center in Research Triangle Park (RTP), N.C., the company announced in a Jan. 5, 2022 press release.

The project, which will feature an additional 89,000 ft

 of laboratory space equipped with state-of-the-art analytical instrumentation, high throughput bioprocessing equipment, and automation technologies, is expected to double the company’s capacity to support process characterization programs and complements the enhanced capabilities at its UK facility. This expansion will also allow Fujifilm Diosynth Biotechnologies to further support its partners in guiding clinical process development that can create more robust commercial processes. 

The expanded space is expected to be operational by mid-2024, which is also when approximately 145 new jobs are anticipated to open up, many of those positions being for researchers and scientists.

“ … We are delighted to be adding this additional capacity to support our growing pipeline of customers,” notes Christine Vannais, chief operating officer, Fujifilm Diosynth Biotechnologies, RTP, North Carolina, in a company press release. “The cutting-edge laboratory equipment and automation tools, combined with the deep technical expertise of our scientific community, will allow us to better serve our partners to rapidly generate and assess data to understand complex molecules, along with the processes used in their manufacture.”

Fujifilm Diosynth Biotechnologies' 89,000 square-foot expansion of its BioProcess Innovation Center in Research Triangle Park, N.C., will double its capacity to support process characterization.

Fujifilm Grows Lab Space at North Carolina Facility

 Washington Editor, jillwechsler7@gmail.com.

In a highly unusual decision for a therapy approved by FDA, the Centers for Medicare and Medicaid Services (CMS) 

 of Biogen’s new and controversial Alzheimer’s treatment Aduhelm (aducanumab). The CMS National Coverage Determination (NCD) did this by 

applying its Coverage with Evidence Development (CED) requirement to the drug

, utilizing a process that has been directed primarily in recent years to a limited number of approved medical products, mainly medical devices and diagnostics. If the proposal is finalized, only patients able to enroll in postapproval trials would have access to the drug.

The aim of the NCD process is to gather further evidence to demonstrate the drug’s potential for improving the health of patients suffering mild cognitive impairment due to Alzheimer’s disease. The CMS policy will authorize access to the drug only to those individuals able to enroll in a clinical trial, most taking place at academic research institutes that CMS will identify and list on its website. Under the accelerated approval granted Aduhelm by FDA’s Center for Drug Evaluation and Research (CDER) in June 2021, Biogen is required to conduct at least one Phase IV trial to demonstrate that the drug’s ability to reduce amyloid in the brain has a broader benefit for patients’ cognitive ability, and that the drug’s serious side effects are limited. Biogen objected loudly to the CMS proposal, noting that it may take years to design and launch postapproval studies, and that such trials will enroll only a limited number of patients. CMS also indicates that its CED requirement will apply to additional monoclonal antibodies targeting amyloid beta in Alzheimer’s disease.

Aduhelm came to market last year amidst heightened controversy over its approval despite limited evidence of efficacy. The debate turned to outrage when Biogen set the price for the new treatment at $56,000 a year. At that level, Medicare spending on the drug was projected to far exceed any other drug if even just a small portion of some 6 million US Alzheimer’s patients sought treatment. In December 2021, after a year of dismal uptake of the drug, Biogen cut its launch price in half to $28,200 a year in an effort to boost prescribing—and avoid a negative NCD from CMS. However, even that reduced cost continued to promise hefty outlays for Medicare. Many leading health centers and physicians said they still would not prescribe the drug due to its limited evidence of efficacy, known side effects and continued too-high cost. The Institute for Clinical and Economic Review (ICER) calculated that Aduhelm would be cost-effective if priced at $3000 to $8000 a year.

In making national coverage decisions, CMS is supposed to evaluate whether a medical product or process is “reasonable and necessary” and not bring cost into the equation. But the fact that a very high number of Medicare patients are potential users of the new drug made that difficult.Before Biogen cut its price, CMS had announced a whopping 15% boost in premiums for the Medicare Part B program, which administers injectables such as Aduhelm. CMS had explained that about half of the premium increase was designed to protect the program against high spending on the new Alzheimer’s therapy. Following Biogen’s cost reduction, Health & Human Services (HHS) secretary Xavier Becerra 

said CMS would reassess the scope of the premium hike

, although the uncertain financial health of the Medicare Trust Fund may deter any significant readjustment in rates.

CMS emphasizes that its CED decision arises from extensive review over the past six months of all relevant published evidence and feedback from stakeholders. The agency opted for the CED process to gain further evidence on whether this new therapy provides any improvement or relief from the effects of Alzheimer’s disease. CMS will accept further public comments on this proposal for 30 days and announce a final coverage decision by April 11, 2022. Alzheimer’s disease groups have called loudly for Medicare coverage of Aduhelm as the only available treatment for the widespread debilitating condition.

It will be interesting to see how the CMS proposal affects other biopharma companies that are testing their own Alzheimer’s therapies. Eli Lilly is conducting clinical trials that directly compare its donanemab to Aduhelm, while Eisai and Roche are moving forward with additional treatments. These and other sponsors now will have to calculate the impact of bringing new drugs to market that would be subject to CED requirements.

Meanwhile, the scientific and medical community continues to criticize the Aduhelm approval. The European Medicines Agency (EMA) recently recommended against approving the drug, and objections have been raised in Canada to a pending review. CMS has navigated its process to greatly limit Aduhelm prescribing and its outlays for the drug, but the debate is far from over.

The Centers for Medicare and Medicaid Services took action to limit prescribing and use of Biogen’s new and controversial Alzheimer’s treatment Aduhelm (aducanumab).

Medicare Limits Aduhelm Coverage to Patients in Clinical Trials

Luc Gagnon, PhD, is vice-president of Vaccine Sciences at Nexelis.

The release of the SARS-CoV-2 virus genetic sequence in January 2020 marked the beginning of an intense period of R&D activity in a race to find effective vaccines to halt the devastating consequences of the global pandemic. The benefits of that unrivalled focus have been made clear. The time from the genetic sequence’s release to the submission of the first vaccine Phase III clinical trial data for regulatory review (from Pfizer–BioNTech) was just 314 days—an unparalleled acceleration of typical timelines that could be more than 10 years for the development of a vaccine in normal circumstances (1).

However, the sheer volume of developers working in the space across a range of modalities (including recombinant viral vectors, live attenuated vaccines, recombinant proteins, and nucleic acids), using different methods of data collection and evaluation, made comparison of immune responses to find the most effective candidates extremely challenging. The unique circumstances called for a shift in vaccine R&D, to an approach focused on collaboration and harmonization. One group at the heart of this shift has been the Coalition for Epidemic Preparedness Innovations (CEPI) centralized laboratory network. The network’s reference labs have effectively transferred a number of assays to laboratories across the globe for a coordinated assessment of SARS-CoV-2 vaccine candidates, allowing for the most efficient global response to the pandemic.

As the SARS-CoV-2 virus began to spread, the Bill and Melinda Gates Foundation (BMGF) and CEPI, a global coalition of public, private, philanthropic, and civil society organizations aimed at accelerating the development of vaccines against emerging infectious diseases, set out to bring much needed alignment and efficiency to the global response, and to ensure the most effective vaccines would reach the most people in the shortest amount of time.

The CEPI centralized laboratory network was established in October 2020 to allow for centralized analysis of samples from vaccine candidate trials to mitigate the risk of variations from independent analyses and to enable head-to-head comparisons of immune responses induced by multiple vaccine candidates (2). The CEPI network is made up of nine laboratories worldwide: Nexelis in Canada; UK Health Security Agency (UKHSA, formerly Public Health England) and National Institute for Biological Standards and Control (NIBSC) in the United Kingdom; VisMederi Srl in Italy; Viroclinics-DDL in The Netherlands, icddr,b (formerly International Centre for Diarrhoeal Disease Research) in Bangladesh; Translational Health Sciences and Technological Institute (THSTI) in India; Q2 Solutions in the United States; and the Universidad Nacional Autónoma de México (UNAM) in Mexico City. The laboratories were selected based on their capacity to perform the necessary studies, but also for their ability to work internationally to harmonize protocols and data.

Developing assays for effective analysis at scale

In February 2020, before the official declaration of the global COVID-19 pandemic, teams at Nexelis and UKHSA began proactive work to develop the immunological tools and reagents that would be required to produce the necessary assays for evaluating the efficacy of the SARS-CoV-2 vaccine candidates on the horizon. Six of these assays across humoral and cellular response, developed and characterized in-house at Nexelis and UKHSA, were selected by the CEPI network to support global SARS-CoV-2 vaccine development programs. Furthermore, these assays have also been used to evaluate the impact of SARS-CoV-2 variants on different vaccines.

To assess the humoral response, experts at Nexelis developed, with complete characterization, the critical reagents to protein targets (pre-fusion full length spike, receptor-binding domain, and nucleocapsid) of SARS-CoV-2 virus for three enzyme-linked immunosorbent assay (ELISA) assays as well as the pseudoparticle neutralization assay (PNA). Meanwhile, the team at UKHSA developed the viral neutralization assay. For assessment of the cellular response for T helper type 1 (Th1) and Th2, Nexelis developed the ELISpot Interferon (IFN)-gamma/Interleukin (IL)-5 assay.

To date, more than 30 assay transfers have been completed between Nexelis and UKHSA to the other recipient labs within the network. As well as ensuring procedures and protocols were in place for the successful transfer within the network, all the assays were also calibrated against the World Health Organization (WHO) international reference standards to ensure harmonization with other labs performing these assays globally.

Within the CEPI centralized network, UKHSA and Nexelis have been identified as the two main reference labs in the overall transfer strategy. Within the first 12 months of the SARS-CoV-2 pandemic, UKHSA and Nexelis managed to develop a toolkit of qualified and validated assays, which played a crucial role in SARS-CoV-2 vaccines and antivirals worldwide to support global public health as well as vaccine companies in their clinical development and regulatory submission process.

The Nexelis protein science team constructed the SARS-CoV-2 pseudo-virus to allow for the viral particles to be handled in a biosafety level (BSL)-2 laboratory. This allowed the Nexelis and UKHSA teams flexibility to develop, qualify, and validate the wild-type plaque reduction neutralization tests (PRNT), micro-neutralization (MNA), and PNA for SARS-CoV-2.

Before reaching the stage at which an assay is prepared for transfer, the production of high-quality reagents (including pseudoparticle against SARS-CoV-2 and its variants) was the first vital step toward ensuring quality control and consistency of assay performance across the network.

Critical agents such as the SARS-CoV-2 pseudovirus are available to labs within the wider CEPI network further demonstrating the value of the public-private partnerships leveraged to establish a new gold standard for vaccine and antiviral development.

Preserving assay effectiveness throughout transfer

Safeguarding the successful transfer of these assays has been critical to the vision of the CEPI network to improve the harmonization of immune response assessment across SARS-CoV-2 programs.

Shipment is always a challenge for successful assay transfers, and the pandemic has added layers of complexity. The network had to address several potential challenges surrounding everything from import permits and documentation for the different viruses and key components, to the implementation of cold chain logistics and dry shippers to maintain the stability of the key reagents throughout the full transportation process.

A thorough protocol, made up of four elements, has been the driving force behind the transfer process between the reference labs and the recipients. Firstly, this includes an assay overview to ensure that everyone involved in the analyses is aligned with how each assay is being performed in the reference labs and understands the limitations of the assays. A gap analysis was completed to highlight any differences between the reference labs and the recipients across key components, including everything from experimental conditions to equipment to the software used for analysis, so that Nexelis and UKHSA could put plans in place during the transfer process to mitigate the potential impact of any differences between testing environments.

A critical component of this gap analysis was comparison of the software used by scientists to aid with calculations for titers and concentrations. The compatibility of this software between the reference and recipient labs continues to pose a challenge. To mitigate the risk of impact to the assay due to differences in calculations, Nexelis provided the validated SoftMax Pro protocol used in their own lab to the recipients. This meant all labs would be using a fully validated GxP protocol to aid in further safeguarding alignment across the network.

Finally, a laboratory comparison assessment and an assay performance evaluation at the recipient labs were completed to ensure that the quality of the assays was not impacted by the transfer.

As the vaccine landscape continues to develop, it is imperative that both the quality and the persistence of the assay transfers can be maintained in the long term. To ensure this, the network is performing aligned assay trending using the Levey-Jennings control chart to assess assay performance overtime and deploying a proficiency panel, which will be tested every six months to ensure the assays are not drifting or trending.

Since the arrival of the wild-type SARS-CoV-2 virus in 2019, the COVID-19 global landscape has continued to evolve with the emergence of new variants of concern. The ongoing analysis of the assays is a vital component of the network’s efforts to ensure it can productively support the development of effective therapeutic candidates against emerging variants of concern, variants of interest, and potential future variants.

The key ingredient for a streamlined approach

The final critical component for the assay transfers was ensuring that the scientists at the recipient labs had access to the necessary expertise to perform the assays themselves. Under normal circumstances, analysts from Nexelis would have travelled to recipient labs to help with transfers but due to the pandemic the reference labs have had to be creative in how they provide essential training and troubleshooting in a virtual format. They created videos and ran full walk-through method standard operating procedure sessions to make sure all scientists were clear on the reality of the assays at Nexelis or UKHSA. They also joined ad hoc teleconferences with recipient lab scientists to regularly align or to discuss any issues such as unexpected results.

This open collaboration and flexibility to work across continents has been critical to the success of the network’s transfer program at every stage during the past 18 months. The ability of eight independent laboratories, competitors in the ‘normal’ world, to work together seamlessly in the pursuit of a shared goal has marked the beginning of a new era of global R&D—one which must continue long after the world emerges from the COVID-19 pandemic, for the benefit of patients everywhere.

1. CEPI, “CEPI Launches Plan to Tackle Risk of Future Pandemics and Epidemics,” Press Release, March 10, 2021.
2. CEPI, “CEPI Establishes Global Network of Laboratories to Centralize Assessment of COVID-19 Vaccine Candidates,” Press Release, Oct. 2, 2020.

The COVID-19 pandemic generated partnerships among organizations with the goal of changing the way in which assay development and tech transfer of these assays are conducted moving forward.