by Charlotte Kilpatrick | Oct 16, 2024 | Technology |
CEPI announced in October 2024 that it is working with experts at the National Research Council of Canada (NRC) to bioengineer a “commonly used approach” to safely make protein antigens in “as little as two weeks”. This would be between eight and twelve times faster than the current timeline of antigen production for protein-based vaccines. CEPI is contributing up to CAD $850,000 and the NRC is providing up to CAD $308,000 (in kind) to establish proof-of-technology.
Low cost and high speed
CEPI notes the importance of manufacturers being able to make “sufficient quantities” of vaccine components at low cost to enable mass production. Although mammalian cell lines are a common choice for vaccine processes, boasting ease of culture and a high production yield, they can take four to six months to develop and optimise for antigen production. This is a “major challenge” to efforts to develop vaccines quickly in response to fast-spreading viral outbreaks.
An optimised approach
Scientists at the NRC have developed a mammalian cell line that could be optimised for rapid antigen production. The research is expected to “majorly accelerate” the time needed for infectious disease vaccine development, says CEPI’s Executive Director of Manufacturing and Supply Chain (Acting), Ingrid Kromann.
“If successful, this optimised cell line could help vaccine doses be more rapidly available for clinical trials and initial emergency use during future outbreaks, supporting CEPI’s goal – embraced by Canada, and other G7 and G20 nations – to respond to a novel virus with a new vaccine in just 100 days after its discovery.”
Importantly, the technology is going to be suitable for transfer to low- and middle-income countries, enabling “local and rapid” vaccine production closer to the source of a future outbreak and improving accessibility. Dr Lakshmi Krishnan, Vice President of Life Sciences at the NRC, looks forward to working with CEPI to take the platform technologies forward to “accessible tools that could help accelerate vaccine production around the world”.
“Recognising the critical need for rapid vaccine production during a health emergency, this research and development project in our labs will advance innovative technologies to improve biomanufacturing processes and increase the efficiency of large-scale manufacturing of vaccines and other biologics.”
For the latest in vaccine technology for improved accessibility, join us at the Congress in Barcelona this month, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 9, 2024 | Technology |
In October 2024, CEPI announced that it is awarding funding of up to £3.7 million to support researchers at the University of Sheffield as they seek proof-of-concept for RNAbox. RNAbox is a specialised process designed to scale up the production of mRNA vaccines at regional vaccine sites. It is “easily adaptable and automated”, with the potential to improve global pandemic readiness by enabling increased equitable access to various mRNA vaccines, as and when needed. It also could help speed up responses to future emerging outbreaks.
Addressing mRNA challenges
mRNA vaccines be “more rapidly tailored” to specific diseases or variants, and the technology “holds promise” for different illnesses, including emerging infectious diseases. However, mRNA vaccines are “expensive to manufacture at a high product quality” and require complex cold-chain storage and transportation infrastructure. This makes them “extremely difficult to deliver to remote areas or low-resource settings”.
The RNAbox presents a potential solution to these challenges through its bespoke manufacturing process, designed to overcome the need to deliver the vaccine by facilitating local manufacture at small production sites. The process will run continuously to create between seven and ten times more mRNA at a time and enable more efficient use of raw materials. RNAbox uses digital-twin technology, in which a virtual replica of the vaccine manufacturing process is modelled on a computer in real-time with smart sensors collecting data on the physical product.
CEPI’s interest
CEPI states that the “fast, optimised vaccine production is critical to the 100 Days Mission”. The investment will explore applying the technology to vaccine development for CEPI priority pathogens, including the viruses that cause deadly diseases like Ebola, Lassa fever, MERS, and Nipah. Ingrid Kromann, Acting Executive Director of Manufacturing and Supply Chain at CEPI suggested that the University’s “versatile” technology “builds on the ‘vaccine revolution’ experienced during the COVID-19 pandemic”.
“It aims to overcome a number of scientific hurdles which resulted in poorer countries facing devastating vaccine inequity by helping to make high-quality, low-cost vaccines quickly and easily close to the source of an outbreak.”
Dr Zoltán Kis, School of Chemical, Materials, and Biological Engineering at the University of Sheffield, reflected on the “importance of being prepared” with the “necessary tools”.
“We need to tackle outbreaks equitably around the world, as diseases can spread across country borders.”
The RNAbox will “accelerate the development of new vaccines” and “mass-manufacturing against a wide range of diseases”.
“This transformative technology can also be used to develop much-needed vaccines against a range of unmet needs during non-epidemic/pandemic times. In case of a new epidemic/pandemic, the RNAbox can be quickly adapted to produce vaccines to tackle outbreaks. This will enable vaccine development and manufacturing capacity locally in countries around the world to serve local needs.”
The researchers will work with vaccine manufacturers in low- and middle-income countries to ensure the technology is fit-for-purpose in lower-resource settings.
At the Congress in Barcelona this month we will hear from experts who are revolutionising mRNA vaccine production to ensure products are accessible. Join us there to learn more, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 19, 2024 | Technology |
An article in Scientific Reports in September 2024 uses Digital Shadows to facilitate a comparison of recombinant DNA and in vitro (IVT) mRNA vaccine manufacturing technologies. The authors offer an assessment of which manufacturing platform is better suited for two types of vaccines. They suggest that recombinant DNA technology exhibits a higher Profitability Index, but mRNA offers faster high potency in short product development cycles.
Technical and economic benefits
Limitations in “traditional vaccines” have “speared” the development of novel technologies for antigens and monoclonal antibodies, including the recent use of recombinant DNA and RNA technologies in the COVID-19 pandemic. Recombinant DNA technology requires the insertion of a gene encoding the relevant pathogen or immunoglobulin sequence into a cell factory organism, which produces the antigen or antibody. RNA technology uses stoichiometric biochemical reactions to produce mRNA (messenger RNA) encoding the antigen or antibody, which is translated in vivo by the recipient’s cells.
Both mRNA and DNA technologies have “established proof of therapeutic effectiveness”. However, they differ in approach to obtaining the therapeutic protein of choice, which leads to different manufacturing processes. For recombinant DNA, the process is “time-consuming and expensive, requiring specialised laboratory facilities and trained personnel”. By contrast, IVT mRNA is understood to be “fast, flexible, and inexpensive”. This is offset by the need for cold transportation and storage to cater to the “instability and sensitivity” of the RNA molecule. Furthermore, IVT mRNA-based vaccine manufacturing has not been standardised.
Both technologies have “captured the global scientific interest” and present opportunities in the treatment of cancer and autoimmune diseases among others. However, the authors state that that there is no comparison of the two technologies on technical and economic levels.
The study
Digital Shadows are “enabling tools suitable to model a system in a fiat cyber-physical environment, delivering data flow abstractions of processing performance”. They are also used in the study to simulate and analyse the “technical merits and production costs” of each technology at given operating conditions. This allows the researchers to investigate root cause deviations and evaluate the cost-effectiveness scenarios of each proposed solution.
The authors constructed Digital Shadows to compare recombinant manufacturing of monoclonal antibodies and antigens with IVT mRNA production processes. They developed algorithmic threads to explore strengths and weaknesses, offering “enabling tools of strategic decision planning”.
The research suggests that recombinant production methods create “highly stable and therefore advantageous products”, with a proven track record of clinical safety and efficacy, and a low risk of unknown side effects, carrier-related allergic reactions, and withdrawals. The vaccines require “minimal maintenance” to preserve stability and functionality, which “ameliorates any respective logistical challenges and minimises the risks related to post-production regulatory withdrawals”. The components needed for production are “accessible” for the pharmaceutical industry but may come under pressure in case of pandemic outbreaks.
A drawback of the recombinant DNA vaccine production platform is its “complicated and therefore difficult-to-automate sub-processes”. The technology requires additional personnel for “process supervision and control purposes”. The platform is therefore “less appropriate for encountering pandemic bursts” or tracking mutations.
Another concern is the high risk of material contamination in cellular protein production, particularly in upstream processing. If contamination occurs, the cell line and its products are discarded, which causes delays and financial losses. Alongside this risk, recombinant DNA and protein production methods feature “low production yield”, which means that raw and side materials are purchased at high quantities and handled by expert personnel to reach the necessary production capacity.
IVT mRNA manufacturing protocols have “strong competitive advantages” in some characteristics. Although the vaccine is “highly sensitive to environmental conditions”, the production process is “easier to standardise, automate, adapt, and operate in continuous mode” thanks to the synthetic chemical nature of its sub-processes. The biochemical section of related processes can offer a “less complex, more effective” alternative with minimal requirements. This reduces the risks of cross contamination and quality-related batch rejections, producing higher yields and limiting product losses; it also lowers raw material processing resources and reduces development time.
Conclusions
For monoclonal antibody products, the study showed that recombinant DNA technology had a higher Profitability Index than IVT mRNA manufacturing. While the recombinant DNA monoclonal antibodies require a significantly higher dose due to an inferior potency profile, this is not reflected analogously in the final production cost. IVT mRNA manufacturing also had “higher dependencies” on raw materials.
When considering antigenic vaccines, the authors found that recombinant DNA technology demonstrated “higher economic performance”, demanding reduced capital resources. It also encompasses “proven, well-grounded protocols” for process development. Recombinant manufacturing “appears advantageous” by meeting technical and financial expectations. However, IVT mRNA “significantly” shortens the timeline from development to clinical application and benchtop to scale manufacturing. It also offers “unparalleled advantages” in synthetic processes and reduced requirements for installing large-scale production equipment.
The paper concludes that clinical trials and field practice will reveal if mRNA technologies can offer non-inferior therapeutic results compared to their DNA recombinant established alternatives. If you have worked with either of these technologies, what are your impressions or predictions? Why not join us at the Congress in Barcelona next month to share your insights into various platform technologies, and don’t forget to subscribe to our weekly newsletters for the latest vaccine news.
by Charlotte Kilpatrick | Sep 13, 2024 | Technology |
In September 2024, WHO announced that the MVA-BN vaccine, manufactured by Bavarian Nordic, is the first vaccine against mpox to be put on the prequalification list. This approval is “expected to facilitate timely and increased access” to the vaccine in “communities with urgent need” amid the outbreak of mpox. The prequalification is based on information submitted by Bavarian Nordic and reviewed by the European Medicines Agency.
Recommended for use
WHO’s Strategic Advisory Group of Experts (SAGE) on Immunisation recommended the use of MVA-BN in an mpox outbreak context for persons at high risk of exposure. It can be administered in over-18s in two doses 4 weeks apart. After initial cold storage it can be kept between 2°C and 8°C for up to 8 weeks.
Although it is not currently licensed for persons under 18 years of age, the vaccine can be used “off-label” in infants, children, and adolescents, and in pregnant and immunocompromised people. This allows use in an outbreak after consideration of the potential risks in relation to the benefits of vaccination.
Data available to WHO reveal that a single-dose MVA-BN vaccine, administered before exposure, has an estimated 76% effectiveness in protecting against mpox; the two-dose schedule achieves an estimated 82% effectiveness. Post-exposure vaccination is less effective. Clinical studies have demonstrated a good safety profile and vaccine performance, which have been confirmed in real-world use during the global outbreak since 2022. However, WHO emphasises the need to collect “as much data as possible on vaccine safety and effectiveness in different contexts”.
An important step
Dr Tedros Adhanom Ghebreyesus, WHO Director-General, described this first prequalification as an “important step in our fight against the disease” with implications for current outbreaks and the future.
“We now need urgent scale up in procurement, donations, and rollout to ensure equitable access to vaccines where they are needed most, alongside other public health tools, to prevent infections, stop transmission, and save lives.”
WHO Assistant Director-General for Access to Medicines and Health Products, Dr Yukiko Nakatani, suggested that the prequalification will “help accelerate ongoing procurement” to help communities “on the frontlines of the ongoing emergency in Africa and beyond”.
“The decision can also help national regulatory authorities to fast-track approvals, ultimately increasing access to quality-assured mpox vaccine products.”
Dr Rogerio Gaspar, WHO Director for Regulation and Prequalification, commented that the findings of the product and programmatic suitability assessments are “particularly relevant in the context of the declaration of a public health emergency of international concern (PHEIC)”.
“We are progressing with prequalification and emergency use listing procedures with manufacturers of two other mpox vaccines: LC-16 and ACAM2000. We have also received 6 expressions of interest for mpox diagnostic products for emergency use listing so far.”
To explore the steps before, during, and after these approval processes in emergency contexts, join us at the Congress in Barcelona this October. Don’t forget to subscribe to our weekly newsletters here for regular updates.
by Charlotte Kilpatrick | Sep 10, 2024 | Technology |
A paper from Vaccines Europe in September 2024 reveals “key vulnerabilities” in the vaccine supply chain and offers strategies to strengthen resilience. The paper addresses the “main causes” of vulnerabilities, how manufacturers are addressing the issues disrupting resilience, and how regulators and policymakers can “enhance” these measures to ensure resilience.
“The underlying principle of vaccine supply chain resilience is that the design of supply chain systems should ensure their capacity to recover critical functions when significant disruptions occur. This resilience is based on robust and agile global supply chains.”
Disruptions can include conflict, health threats, or “catastrophes caused by climate change”, and addressing these events demands a “thorough understanding of key vulnerabilities” in the supply chain and the ability to “respond with flexibility and agility”.
Vaccine vulnerabilities
The authors acknowledge the various stages of vaccine development and delivery from manufacturing and testing to regulatory requirements. Vaccines are “often highly technical, complex biological products”. Although the COVID-19 vaccines had a shorter production lead time, the general production lead time is over a year. Additionally, the “complexities and strict requirements of daily performance” affect the vaccine supply chain.
The time required for designing, building, validating, securing regulatory approvals, and starting commercial manufacturing and distribution of a vaccine ranges between 5 and 10 years. Specific manufacturing processes and facilities hinder the expansion of manufacturing capacity when demand increases.
Another limiting factor is the need for different languages on vaccine packs and leaflets; multi-lingual packs are “limited to a maximum of three languages”. This means that “at least 14” different packs are needed for a single presentation of a centrally approved vaccine for coverage across all EU/EEA countries. Manufacturers must “cluster production”.
The COVID-19 pandemic highlighted that “lack of transparency” at any stage in the supply chain can increase the risk of supply shortages. The combination of “unpredictable” demand and a lack of dialogue between manufacturers and health authorities contribute to supply shortages. While some countries conduct “horizon scanning”, other countries do not have these mechanisms in place.
Other factors contribute to supply shortages:
- Environmental factors
- Geopolitical factors
- Economic factors
- Technological factors
- Regulatory factors
- Tender practices
Addressing issues: manufacturers
“Manufacturers are committed to maintaining the supply of vaccines to the community and are therefore implementing a series of measures to reduce potential supply disruptions, where possible and appropriate.”
To deal with threats, vaccine manufacturers have “multiple mitigation plans”:
- Quality systems – good manufacturing practices, staff training, employing qualified personnel, validation of new equipment and facilities
- Proactive risk management (multi-sourcing) – multiple sources for raw materials
- Supply continuity plans – strategies to ensure product delivery is maintained during disruptions
- Fit-for-purpose shortage prevention plans – a risk management process focusing on manufacturing capabilities, sourcing of raw materials, market trends, marketing activities, and product supply
- Updated business contingency plans – plans to resume normal business operations after unintended interruptions like natural disasters, data loss, or demand shifts.
- Diversity of geographical locations of key suppliers – prevents reliance on supplies from the same country/region if disruptions occur
- Inventory management – systems designed to monitor stock levels and order demands
Addressing issues: regulators and policymakers
“Regulators and policymakers can help enable strategies already being employed by vaccine manufacturers and ensure any future policy solutions are proportionate to the risk, carefully considering unintended effects and backed by strong evidence on the nature of shortages.”
Strategies to achieve this include:
- Improving demand forecast transparency: manufacturers must be able to access information on needs and employ a coordinated mechanism for vaccine allocation. The EU and Member States should ensure regulatory expertise and resources and enhance transparency in the decision-making process regarding vaccine assessment. Constant communication with suppliers ensures transparency and successful planning on policy and programme implementation. Data sharing also allows understanding of demand.
- Implement successful strategies from the COVID-19 pandemic during non-pandemic times: policies should support manufacturing capacities, free trade of raw materials and vaccines, and the freedom to select suppliers. Removing export restrictions, opening borders, and ensuring diversified supply chains are “key”. Supply chains can also be strengthened with improved distribution channels to “alleviate bottlenecks”. During the pandemic, “official green lanes (or corridors)” were established to facilitate customs clearance at border crossings. Additional “dialogue on open supply chains with like-minded countries” are “critical in driving sustainable and globally aligned approaches”. Harmonised regulatory standards also provide “system-wide benefits”; the pandemic showed that rolling submissions, potential for electronic or hybrid inspections, conditional marketing authorisations, and acceptance of the EU common pack and electronic Patient Information Leaflet accelerated access. Here, again, information and data sharing are “essential for improved understanding of vaccine demand forecast”.
- Encouraging stakeholder collaboration to create synergies for strengthened resilience: “essential synergies” ensure understanding of the vaccine production process, avoid delays and duplication of work, and shape future activities. Stakeholders must be effectively engaged, and “diverse modes of collaboration” will allow vaccine development within tight timeframes. Communication between national, EU, international health agencies, authorities, and manufacturers is “critical”. Key partnerships during the COVID-19 pandemic “bolstered manufacturing capacity”, enabled technology and knowledge transfer, accelerated research and development, and encouraged “unprecedented” manufacturing scale-up.
- Reducing packaging complexities: the authors encourage the adoption of a common EU packaging accepted by Member States and replacing the paper patient information leaflet with an electronic version (ePIL). Regulatory flexibilities would allow redeployment of inventory between countries.
- Ensuring a highly skilled vaccine manufacturing and supply chain workforce: policy priorities include “upskilling” the EU vaccine workforce and providing support to Member States for improved research, development, and manufacturing capabilities; varied infrastructure and workforce capabilities demand investment.
Collaboration
“Addressing these root causes is largely beyond the control of manufacturers alone and will require mutually feasible and sustainable solutions in collaboration between competent authorities, governments, and industry.”
Vaccines Europe concludes that a complete understand of the end-to-end vaccine production and batch release processes is critical to preventing delays. Optimising collaboration, minimising duplicate efforts, and increasing resilience and agility for the future will “ultimately improve vaccine availability and contribute to better public health”.
We look forward to welcoming Vaccines Europe to the Congress in Barcelona this October for sessions on vaccine development and policy. Get your tickets to join us there, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 4, 2024 | Technology |
3PBIOVIAN announced in September 2024 that it has been selected by Rokote Laboratories Finland Ltd. as CDMO partner for GMP manufacturing of adenovirus type 5 (Ad5) vector-based candidate expressing a modified SARS-CoV-2 spike protein. The partnership aims to bring Rokote Laboratories’ intranasal FINCoVac 2.1 vaccine to Phase I clinical studies with 3PBIOVIAN providing Drug Substance and Drug Product. FINCoVac 2.1 is intended to elicit a strong mucosal immune response in the nasopharyngeal cells, potentially preventing infection and transmission.
Ad5 vector
The agreement covers GMP manufacturing of the Ad5 vector using 3PBIOVIAN’s standard process at facilities in Turku, Finland. With “extensive experience” in adenovirus GMP manufacturing solutions, 3PBIOVIAN pursues “successful scalability and GMP compliance”. To meet Rokote Laboratories’ “urgent” needs, the programme has advanced “exceptionally fast”.
FINCoVac 2.1
Rokote Laboratories seeks to “consolidate” the use of new vaccine technology in Finland, focusing on a second-generation coronavirus vaccine, FINCoVac 2.1. It is designed to “meet the challenge of the rapidly mutating variants” with applications as an “easy-to-dose booster”. The vaccine consists of an adenoviral vector, to which the SARS-CoV-2 viral spike protein gene has been transferred. FINCoVac is administered intranasally, so it is expected to offer a “wider immune response” than vaccines that are administered intramuscularly.
Dr Erkko Ylösmäki, CEO of Rokote Laboratories, is pleased with the partnership with 3PBIOVIAN to manufacture the vaccine.
“The ability to use 3PBIOVIAN’s standard process for rapid GMP batch production, along with their extensive experience with adenovirus-based processes, made 3PBIOVIAN the ideal CDMO partner.”
Dr Ylösmäki is excited to start the collaboration and hopes that “together we can further advance Finnish vaccine development”. Deputy CEO at 3PBIOVIAN, Antti Nieminen, commented that the company has “about two-decade-long history” in viral vector development processes and GMP-manufacturing of adenoviruses.
“We are happy to have a role in the journey of this novel second-generation coronavirus vaccine to clinical trials.”
For the latest vaccine manufacturing insights and updates at the Congress in Barcelona this October, get your tickets here, and make sure you’ve subscribed to get our weekly newsletters.
by Charlotte Kilpatrick | Aug 12, 2024 | Infection |
In August 2024 WHO issued an invitation for manufacturers of mpox vaccines to submit an Expression of Interest for Emergency Use Listing (EUL). This came shortly after the Director-General, Dr Tedros Adhanom Ghebreyesus, announced that he has decided to convene an Emergency Committee under the International Health Regulations to advise on the need to categorise the outbreak as a public health emergency of international concern (PHEIC). As the outbreak evolves and cases are reported in previously unaffected regions, WHO is making efforts to ensure resources are available to address the situation.
Director-General’s comments
At a media briefing on 7th August 2024, Dr Tedros Adhanom Ghebreyesus stated that the DRC has reported more than 14,000 mpox cases and 511 deaths since the beginning of the year. Although DRC has been reporting outbreaks of mpox “for decades”, the number of reported cases has been “increasing steadily” every year. The number of cases reported in the first six months of this year “match the number reported in all of last year”. Additionally, recent confirmed and suspected cases have been reported in DRC-neighbouring countries that have previously not reported cases: Burundi, Kenya, Rwanda, and Uganda.
The Director-General noted that the current outbreak in the Eastern DRC is caused by a “new offshoot” of mpox clade I, known as clade 1b. This causes “more severe disease” than clade 2, which caused the 2022 global outbreak. In other parts of DRC, along with Central African Republic and the Republic of Congo, cases of clade 1a have been reported. Clade 2 is reported in Cameroon, Côte d’Ivoire, Liberia, Nigeria, and South Africa.
While WHO works with governments in the affected countries, Africa CDC, and partners, to “understand and address the drivers” of the outbreaks, Dr Tedros highlighted the need for a “comprehensive”, community-centred response. Dr Tedros elected to convene an Emergency Committee, setting the date for Wednesday 14th August. This step will bring expert advice on whether the outbreak is a public health emergency of international concern. From there, Dr Tedros will be advised on temporary recommendations for prevention and disease management.
Vaccines to the fore
Two mpox vaccines have been approved by WHO-listed national regulatory authorities and are recommended by WHO’s Strategic Advisory Group of Experts on Immunisation (SAGE). Dr Tedros has “triggered the process” for Emergency Use Listing (EUL) of both vaccines to accelerate vaccine access, particularly for lower-income countries. EUL also allows partners like Gavi and UNICEF to procure vaccines for distribution.
WHO also issued an invitation for mpox vaccine manufacturers to submit an Expression of Interest for EUL. The procedure is “specifically developed to expedite the availability of unlicensed medical products” for use in public health emergency situations. WHO requests that manufacturers submit data to demonstrate that their vaccines are safe, effective, of assured quality, and suitable for target populations.
At the Congress in Barcelona this October, we will hear from vaccine safety experts about post-authorisation safety and effectiveness evaluation of vaccines that are deployed through emergency use authorisation. To join us, do get your tickets here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Jul 31, 2024 | Global Health |
In July 2024 the Regionalised Vaccine Manufacturing Collaborative (RVMC) shared its strategy for 2024-2027, launched by Dr Frederik Kristensen, Inaugural Managing Director. Dr Kristensen states that the strategy comes at a time of “considerable interest and activity around regional vaccine manufacturing”.
“Spurred on by the deep inequities in vaccine access experienced during the COVID-19 pandemic, the past two years have seen a surge in public and private investments in regionalised vaccine manufacturing.”
The strategy suggests that regional consolidation will achieve the necessary scale of “demand, investment, and capability” to “maintain viable and sustainable vaccine production”.
RVMC
RVMC was launched by the World Economic Forum (WEF), the US National Academies of Medicine (NAM), and CEPI in 2022 with the goal of tackling the “glaring inequities within the global vaccine production ecosystem”. Its vision is a “world where vaccine equity and health security are created for countries in all regions”, which can be realised through the establishment of regional vaccine manufacturing and supply chain networks that can produce vaccines for routine use in a “sustainable manner”, with outbreak readiness.
The first phase of RVMC was focused on building a robust partner community, fostering regional collaboration, and developing the RVMC Framework. The Framework outlines eight pillars for a sustainable vaccine manufacturing ecosystem:
- Business archetypes
- Healthy markets
- Financial models
- R&D and manufacturing innovation
- Technology transfer and workforce development
- Supply chain and infrastructure
- Product regulation
- Policy and governance
In January 2024 the founding parties confirmed the continuation of RVMC for the coming three years, with support from key partners such as PAHO and Africa CDC. For this phase, RVMC is seeking to create value by:
- Advocating for regionalised manufacturing
- Aligning key initiatives
- Advising on approaches
- Accounting for progress
Advocating for change
RVMC will “make the case” for regionalised vaccine manufacturing, setting out a global vision for the “regionalisation agenda” and enabling others to “define and implement their regional approach”. It will build consensus around what regionalised vaccine manufacturing means and establish policy positions and access to data. Raising awareness and engagement with a global vision will “foster a common approach” between partners. This step will be facilitated by “thought leadership and evidence generation”.
Aligning partners for impact
Discussions will be held within and between regions and stakeholders, with RVMC working to align projects to “common objectives and regional priorities”. The strategy highlights the importance of “convening partners around a unified vision” to ensure that available resources are used efficiently, and in a “coordinated and coherent manner”.
“Better coordination should generate more impact and encourage further investment in the regionalisation agenda, therby improving the economic sustainability of vaccine manufacturing. Independent convening, matchmaking, and facilitating dialogue will be key enablers of this work.”
Advising on sustainable approaches
Independent trusted advice will be offered to stakeholders by RVMC, with a focus on expanding the “fact base” for current global and regional capacity, capabilities, and coverage. This element will “champion existing data providers” and identify data gaps. For example, it is currently “not clear” what manufacturing capacity is already in place, and what additional resources will be needed to make regionalised manufacturing a reality. Thus, publishing this position with perspectives on what is needed will support manufacturers who are trying to develop viable business models, funders hoping to support regional supply chains, and stakeholders working on the creation of healthy markets.
Accounting for progress
Following the Framework, RVMC will “observe and report on progress” across the eight pillars. This will enable all stakeholders to “see the whole picture” and the Secretariat to identify areas of need. It also feeds into the ongoing Advocacy role and could provide insights and encouragement for attracting sustainable investment.
The perfect opportunity
Dr Kristensen believes that RVMC is “uniquely suited” to providing stakeholders with the support they need; it is “fully dedicated to the vaccine regionalisation agenda” and is “intentionally positioned between regions and between global and regional bodies”.
“We’ve never had a better chance to advance vaccine equity and health security for all than now, and through our 2024-2027 strategy we’re committed to working with all partners to create regional vaccine manufacturing as a core element to deliver this.”
We’re looking forward to exploring regional vaccine manufacturing at the Congress in Barcelona this October in a panel on regional capacity and resilient systems. Get your tickets to join us here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Jul 29, 2024 | Technology |
In July 2024, WHO announced that Argentine manufacturer Sinergium Biotech is to lead a new project that aims to accelerate the development and accessibility of human avian influenza (H5N1) mRNA vaccine candidates for manufacturers in low- and middle-income countries (LMICs). The project will leverage the WHO and Medicines Patent Pool (MPP) mRNA Technology Transfer Programme, which was launched in July 2021 to build capacity in LMICs for the development and production of mRNA-based vaccines. Sinergium is a partner in the Programme and has developed candidate H5N1 vaccines. If it establishes preclinical proof-of-concept the technology, materials, and expertise will be shared with partners, “aiding the acceleration” of the development of these candidates and “bolstering pandemic preparedness efforts”.
The mRNA Technology Transfer Programme
Since its inception, the mRNA Technology Transfer Programme has already developed and implemented a platform that has been used to establish the immunogencity, efficacy, and safety of a COVID-19 vaccine candidate in preclinical models. The platform was created and validated at Afrigen and is now being shared with partners for applications against “other critical disease targets”.
WHO Director General Dr Tedros Adhanom Ghebreyesus, states that the initiative “exemplifies” why WHO established the Programme to “foster great research, development, and production”.
“When the next pandemic arrives, the world will be better prepared to mount a more effective and more equitable response.”
Charles Gore, MPP’s Executive Director, reflected that the goal of the Programme is to “enable low- and middle-income countries to lead development efforts, foster collaboration, share resources, and disseminate knowledge”.
“This project embodies our vision and demonstrates a strong commitment to future pandemic preparedness and response.”
Rising to the avian influenza challenge
WHO states that avian influenza viruses are a “significant public health risk” due to “widespread circulation in animals” and “potential to cause a future pandemic”. Thus, the latest project complements work to improve and strengthen the sharing of influenza viruses with human pandemic potential and increase LMIC access to vaccines. Dr Jarbas Barbosa, Director of the Pan American Health Organisation (PAHO), is pleased with the news.
“This announcement underscores the importance of not only geographically diversifying the innovation and production of health technologies including and recognising the capacities in Latin America and the Caribbean, but also the importance of early planning for access and the sharing of knowledge and technologies during the research and development processes.”
Chief Executive Officer at Sinergium is “excited to tackle this public health challenge” in collaboration with partners.
“Sinergium’s enhanced capacity and readiness to apply our expertise to H5N1 will play a vital role in this effort towards global pandemic preparedness. I would also like to thank PAHO who have also been instrumental through the strong support it offers to regional manufacturers in the Americas.”
The importance of technology transfers in building regional capacity and facilitating equitable vaccine distribution will be discussed in a panel at the Congress in Barcelona this October; get your tickets to join us here and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Jul 3, 2024 | Technology |
In July 2024, GSK and CureVac announced that they have “restructured” an existing collaboration into a new licensing agreement to allow both companies to “prioritise investment and focus their respective mRNA development activities”. The two companies have been working together on mRNA vaccines for infectious diseases since 2020. This collaboration has led to the development of vaccine candidates for seasonal influenza and COVID-19 (Phase II) and avian influenza (Phase I).
CureVac’s mRNA
The candidates are based on CureVac’s proprietary second-generation mRNA backbone. CureVac states that mRNA has “unparalleled potential as a drug”, which is driving an “exciting mission” into “unexplored territory”. The team analysed millions of naturally occurring sequences to gain insights into the endogenous RNA language, which enabled them to develop an in-house nucleotide sequence library to “optimally assemble the various pieces of the mRNA puzzle”.
The agreement
Under the terms of the new agreement, GSK will assume control of developing and manufacturing the vaccine candidates, with worldwide rights for commercialisation. This is the “latest step in GSK’s ongoing investment in vaccine platform technologies”, through which the company matches the best platform to specific pathogens to create best-in-class vaccines.
CureVac will receive upfront payment of €400 million and up to €1.05 billion more in development, regulatory and sales milestones, and tiered royalties. This agreement replaces all previous financial considerations from the prior collaboration agreement. CureVac will also retain exclusive rights to the additional undisclosed and preclinically validated infectious disease targets from this collaboration, with the opportunity to independently develop and partner mRNA vaccines in any other infectious disease or other indication.
Vaccines at pace
Dr Tony Wood, GSK’s Chief Scientific Officer, is “excited” about the flu/COVID-19 programmes and the “opportunity to develop best-in-class mRNA vaccines to change the standard of care”.
“With this new agreement, we will apply GSK’s capabilities, partnerships, and intellectual property to CureVac’s technology, to deliver these promising vaccines at pace.”
Dr Alexander Zehnder, Chief Executive Officer, CureVac, states that the new agreement “puts us in a strong financial position and enables us to focus on efforts in building a strong R&D pipeline”.
“The collaboration with GSK has been instrumental in developing promising, late clinical-stage vaccine candidates, leveraging our proprietary mRNA platform.”
For more from senior representatives of GSK at the Congress in Barcelona this October, get your tickets here. Don’t forget to subscribe for weekly vaccine updates here.
by Charlotte Kilpatrick | May 30, 2024 | Global Health |
In May 2024, Gavi and CEPI announced the expansion of their partnership to “enhance the rapid development, deployment, and access to vaccines” against deadly disease threats with outbreak potential. The partners, who lead COVAX during the height of the COVID-19 pandemic, signed a two-year Memorandum of Understanding to facilitate “faster sharing of global health and vaccine information” between the two organisations to “better prepare for and respond to future epidemics”.
“The goal is to use CEPI and Gavi’s respective areas of expertise to accelerate equitable access to outbreak vaccines for populations most in need, regardless of their ability to pay.”
Learning from COVID-19
The Memorandum of Understanding was signed at the 77th World Health Assembly and capitalises on the “strong relationship” that exists between the two organisations. This was developed during the COVID-19 pandemic. Despite “successes”, the organisations identify a clear need to “create an end-to-end solution” to ensure we are better prepared for a future viral threat with pandemic potential.
Dr Richard Hatchett, CEO of CEPI, reflected that, “despite COVAX’s valiant efforts”, the COVID-19 pandemic “exposed the deep tragedy of unequal access to life-saving medicines”.
“Now, as we seek to recover from the pandemic and prepare for new threats, it’s vital that we re-engineer the system to produce better outcomes for everyone in the future: the COVAX motto of ‘no one is safe until everyone is safe’ holds true today.”
Dr Hatchett believes that this continued partnership will “deliver a more cohesive strategy” to improve “speed, scale, and access” to vaccine doses against future emerging viral threats. Dr Sania Nishtar, Gavi’s CEO, commented that the organisations “played a formative role” in “shaping” the global vaccine response when COVAX was designed in early 2020.
“We learnt a lot along the way about how to build a future response that is faster, more equitable, and scalable.”
Dr Nishtar suggests that the Memorandum of Understand “will ensure both Gavi and CEPI are able to bring their core strengths” in a “coordinated response” against future threats.
Areas to address
Current and future focuses for the collaboration include “alignment and coordination” on the development, manufacturing, and supply of new vaccine candidates against known diseases, as well as Disease X.
“The faster that safe and effective new vaccines are developed and equitably deployed based on a country’s need, the faster a new pandemic threat can be contained and controlled, helping to reduce the threat for everyone, everywhere.”
The collaboration also involves “policy and advocacy efforts” to “enhance the global pandemic preparedness architecture”. Specific activities within the Memorandum of Understanding will be shared after discussions between the organisations over the coming months.
We look forward to welcoming senior representatives of both Gavi and CEPI back to the Congress in Barcelona this October; get your tickets to join us and don’t forget to subscribe for more updates!
by Charlotte Kilpatrick | May 29, 2024 | Technology |
In May 2024 CEPI announced that it is expanding its strategic partnership with BioNTech to contribute to “building a sustainable and resilient end-to-end African vaccine ecosystem”. CEPI commits up to $145 million to support BioNTech’s efforts to establish mRNA vaccine R&D, clinical, and commercial-scale manufacturing capabilities in Kigali, Rwanda. These capabilities will support preparations for potential future epidemic and pandemic threats in Africa.
BioNTech in Africa
BioNTech inaugurated the commercial-scale manufacturing facility in Kigali in December 2023. It is based on BioNTainers, high-tech, digitally enabled modular manufacturing units that are designed to manufacture mRNA-based vaccines. CEPI suggests that the facility could become the first commercial mRNA facility in Africa. It is intended to support the African Union and Africa CDC goal of producing 60% of total vaccine doses required on the continent by 2040. BioNTech intends to provide “affordable access” to BioNTech’s prophylactic vaccines manufactured at the facility; this includes vaccines against malaria, mpox, and tuberculosis.
“BioNTech and CEPI intend to work jointly to rapidly respond to outbreaks on the African continent caused by known viral threats or an as-yet-unknown pathogen with epidemic or pandemic potential.”
Three key areas
The partnership will support BioNTech’s existing efforts in three key areas:
- Commercial-scale manufacturing: CEPI’s funding will support measures required for the regulatory authorisation of the facility in Rwanda from 2025. Should an outbreak occur, BioNTech would dedicate “up to half” of the facility’s manufacturing capacity for emergency response mRNA vaccines, subject to regulatory authorisation.
- End-to-end clinical-scale manufacturing of novel vaccine candidates: the majority of the funding will be allocated to establishing clinical-scale manufacturing capabilities for mRNA-based vaccine candidates at the facility. This would allow manufacturing on both a clinical and commercial scale, broadening the manufacturing scope and supporting a sustainable use case for the facility while “strengthening the wider African vaccine development ecosystem”.
- Strengthening the African R&D ecosystem for mRNA-based vaccines: CEPI’s funding will enable BioNTech to dedicate manufacturing capacities to third party projects with the aim of supporting pre-clinical and clinical activities. The projects would be selected in partnership with global, regional, and national healthcare organisations. This effort has the potential to enable R&D activities for novel mRNA-based vaccine candidates against pathogens with epidemic or pandemic potential.
Resilience and readiness
Dr Richard Hatchett, CEO of CEPI, reflected that Africa still imports 99% of all the vaccines it needs, meaning “many are left waiting far too long to get the life-saving doses they need”. He demands change “if the world is going to avoid the terrible inequity of vaccine distribution that so clearly exacerbated the effects of the COVID-19 pandemic”.
“Through our joint commitment to equitable access, CEPI’s investment in BioNTech’s forward-looking efforts in Africa will boost regional capacity for end-to-end research, development, and rapid manufacturing of mRNA vaccines. This will contribute to Africa’s resilience and pandemic readiness and could dramatically alter the course of future outbreaks.”
Professor Uğur Şahin, CEO and Co-founder of BioNTech, described the partnership as an “important next step” in the “comprehensive strategy towards sustainable mRNA vaccine manufacturing in Africa”.
“Our joint efforts are strengthening the implementation of a local mRNA vaccine ecosystem – covering the entire spectrum from research and clinical trials to commercial production. This, along with our continued efforts to develop mRNA vaccines against diseases like tuberculosis, malaria, HIV, and mpox, is aimed at bringing lasting health benefits to millions of people in Africa.”
Experts comment
Minister of Health for Rwanda, Dr Sabin Nsanzimana, emphasised the government’s commitment to “tackling vaccine inequities that were exposed during the pandemic”.
“We believe this innovative partnership we are building can be a demonstration to the world that Africa is not only building resilience for future pandemics but also creating a sustainable clinical ecosystem across Africa using the most advanced mRNA technology.”
Dr Nsanzimana shared that the “power of partnership” will make the project successful.
“Today is another great milestone towards creating vaccine equity.”
H.E. Dr Jean Kaseya, Director General of Africa CDC, said that “rapid and equitable access” to these life-saving vaccines “start with local development and manufacturing”.
“CEPI and BioNTech’s joint endeavour in Rwanda will contribute to Africa’s R&D ecosystem and support Africa CDC’s Platform for Harmonised African Health Products Manufacturing (PHAHM)’s goal to produce 60% of the vaccines needed by the continent by 2040. Working together, we can pave the way to strengthen Africa’s pandemic preparedness and health security.”
WHO Director-Director General, Dr Tedros Adhanom Ghebreyesus, stated that the “COVID-19 pandemic exposed the risks to global health when production of vaccines and other tools is concentrated in too few hands”.
“Strengthening local and regional production, especially in Africa and the Middle East, is critical for ensuring a more equitable response to future epidemics and pandemics, and for fighting other persistent health challenges. Public-private partnerships like this are part of a growing global movement, bringing together companies, foundations, and countries to diversify production and make the world a safe place.”
This should be seen as a “stepping stone” for other countries and parties to “come together”.
We look forward to discussing mRNA manufacturing in Africa at the Congress in Barcelona this October; do get your tickets to join us there and don’t forget to subscribe to our newsletters here.
by Charlotte Kilpatrick | May 16, 2024 | Technology |
Our next interview from the Congress in Washington is a conversation with Vernal Biosciences‘ Dr Grant Henderson, who joined us at the event to discuss “accelerating mRNA and LNP manufacturing with platform analytical and process technologies”. The Vernal team also shared two posters in our poster zone; links to these can be found below. Dr Henderson is Vernal’s Senior Director of Commercial and Technical Operations and has recently shifted into this role to help researchers accelerate their journey from lead identification through candidate selection, and on to IND and commercial supply.
Accelerating manufacturing
We asked Dr Henderson for an insight into the content his session on accelerating mRNA and LNP manufacturing, and he emphasises that the team has “gone out of our way” to develop a seamless mRNA platform that reaches as far back as the research stage of an asset.
“Customers can come to us, we’ll give them research grade material, and from there it just develops all the way through; we can support them through their clinical manufacture and commercial.”
Talking technology
Our next question considers the technology or strategy that Vernal is using in its goal of “making mRNA readily available“.
“The technology is versatile, so it’s a platform that takes us all the way through from the strain development up to the LNP formulation.”
This can be done across a broad range of manufacturing scales with two different quality standards: the first offer for research grade (RUO) uses “open processing type equipment with reusable parts” , while the CGMP offering uses “fully single use” equipment, operating in a CGMP space.
Unmet need or fierce competition?
We next asked Dr Henderson about the company’s profile; is it meeting an unmet need or distinguishing itself from many competitors? He suggests that it’s “yes to both”!
“We look at it more of as an unmet need.”
Dr Henderson explains that his team helps early-stage companies solve hard problems around mRNA and LNP supply, including scale, and process and analytical development. With more mature companies, Vernal is able to accept all or the most robust aspects of their process and analytical technology and make improvements around the edges. They don’t expect customers to compromise on quality, regardless of their stage of research and development.
Dr Henderson identifies a lack of options to “get your product all the way through to commercial” or Phase I clinical manufacturing without partnering with a larger company. Vernal works with companies with “really exciting technology”, designed to accelerate the path to life-changing medicines, who need a purpose-built CDMO to deliver high purity, research grade and CGMP, drug substance, drug product, and intermediates.
Why WVC?
Finally, we cover the reasons for Vernal’s presence at the Congress. Dr Henderson comments on the “diverse set of exhibitors”, comprising both potential customers and competitors.
“Really it’s the entire cross-section of the market that Vernal is in.”
Vernal’s posters at WVC
Vernal also presented two posters during the Congress – click the links below to learn more!
Novel plasmid DNA-encoded poly(A) tails for mRNA synthesis: this study evaluates the stability of variant poly(A) regions, which are essential for the translation and stability of mRNA, and evaluates the biological activity of the mRNA containing the variant poly(A) tails.
mRNA capping technologies – effects on quality attributes, biological effects, and innate immune stimulation: this study compares two important mRNA capping technologies by evaluating mRNA integrity, percent Cap1 content, dsRNA content, in vivo expression, and innate immune activation in mice.
It was great to meet Dr Henderson and we hope that you enjoy the conversation.
For more conversations with our experts from the Congress in April do make sure you subscribe for weekly updates here!
by Charlotte Kilpatrick | Mar 19, 2024 | Technology |
In March 2024 the University of Birmingham announced that it is leading UK-wide training to “address critical skills demand in life sciences”. A new national Centre of Excellence, the RESILIENCE Centre of Excellence for UK Medicines Manufacturing Skills, will deliver training, materials, and programmes to address skills demands in the life sciences sector. It is run by an academic consortium of UK universities. The Centre will receive £4.5 million of funding from Innovate UK and the Office for Life Sciences and work with healthcare and pharmaceutical organisations to offer an “entry point” for training and career input.
School children are also expected to benefit from the Centre through free resources to 150 schools, colleges, and universities as well as education, mentoring, and outreach to “nurture the talent pipeline”. For the existing workforce, training courses will be developed to “ensure that the UK remains at the forefront of medicines development” and is prepared to fight future pandemics. Life Sciences businesses will be “key partners” to ensure that training needs are adapted to suit “pressing priorities”.
These current needs include training provision for digital skills, data analytics, and AI as well as embedding environmental sustainability into manufacturing processes. Combining virtual reality and mixed reality delivery modes will enable staff to undertake more training in VR than the physical environment, which reduces the production of manufacturing waste and speeds up the process.
A skills shortage
Professor Ivan Wall, Co-Director of Resilience, identifies a “critical and growing skills shortage” in the medicines manufacturing industry.
“The RESILIENCE Centre of Excellence will bridge this skills gap, by developing a pipeline of talent and providing training for industry to ensure current and future employees possess the right skills for a rapidly evolving sector.”
Professor Wall suggests that RESILIENCE will work with industry and government to “build training and outreach programmes” to enable “workforce growth” to “boost” the country’s manufacturing capacity.
“Innovative training technologies, such as VR and AI, will give trainees access to virtual replicas of industry facilities, enabling them to become ‘workplace ready’ without the safety risks or environmental impacts of physical equipment. This approach will allow us to standardise and scale out training provision across our core partners, ensuring consistency in skills development across the UK.”
Professor Gary Lye, Director of the University College London Manufacturing Future Lab, considers it important to “support this vital sector through new research and through education of the skilled individuals who will enable the sector to grow”. At a Maths Summit at the Science Museum in London in March 2024, Science and Technology Secretary Michelle Donelan commented on the importance of collaboration to build on “reforms to the skills system”.
“By doubling down on our investments in skills and backing British business, we can lay the foundations for an economy fit for the future – an economy that creates jobs and improves lives for communities up and down the country. This is how we make our science and tech superpower mission a success.”
Professor Vikki Rand, Director of Teesside University’s National Horizons Centre, emphasised the “strong track record” that the Centre has for “working with partners in the bioscience sector developing innovative training for the workforce”.
“By combining hands-on training on the latest equipment with digital technology, including VR and AR, we deliver real impact for the companies, by saving quality time and resources and giving them the ability to train their employees at scale.”
Professor Rand is “delighted” to participate in the “excellent national project” to ensure that the UK “retains its leading place in biomanufacturing”.
“We are looking forward to delivering a real step-change in driving the talent pipeline to manufacture medicines of tomorrow.”
Heriot-Watt University’s Professor Nik Willoughby is “thrilled to participate in RESILIENCE” and contribute to the education of the next generation with “essential skills for the development and manufacture of future medicines”.
“Our emerging Global Research Institute in Health and Care Technologies exemplifies our commitment to advancing healthcare through innovative research-led teaching and entrepreneurial collaboration.
Dr Kirk Malone, Commercial Director of Britest Limited, appreciates the importance of skills training and development from the perspective of “an SME-sized company that supports organisations to sustainably grow through better process understanding”.
“RESILIENCE will instil multidisciplinary thinking into future skilled workers to enable more sustainable medicines manufacturing.”
To join us to participate in discussions about the future of bioprocess and manufacturing at the Congress in Washington this April, get your tickets here, and don’t forget to subscribe to our newsletters.
by Charlotte Kilpatrick | Feb 28, 2024 | Technology |
In written evidence submitted to the Committee for Science, Innovation, and Technology for the inquiry into lessons from the pandemic Dr Clive Dix details recommendations from the Vaccine Task Force (VTF) from 2020. The evidence was made public in an “unusual step” in February 2024. Dr Dix, now Chief Executive Officer at C4X Discovery, was “instrumental” in the Task Force’s work and findings. The recommendations, initially prepared in December 2020 are annotated with comments from January 2024.
In the recommendations, Dr Dix stated that the pandemic demonstrates the need for the UK to “be part of a rapid response system to discover and develop vaccines” and ensure it has a “resilient supply of vaccines and antibodies new and old”.
“We need to act quickly to prevent pandemics occurring, so the UK needs a permanent ecosystem for rapidly developing, manufacturing, and supplying vaccines for future pandemics, ensuring domestic resilience and security, while also creating long term economic prosperity.”
To “cement” the UK’s position as a “global leader”, Dr Dix called for a “diverse, informed infrastructure for surveillance of adverse events, flexible capacity for manufacturing and testing vaccines, and a global funding facility for purchasing and distributing vaccines internationally”. To allow vaccines to “play an effective part of pandemic recovery and preparedness”, Dr Dix stated that they must be “available quickly and be manufacturable at scale”.
What are the recommendations?
The recommendations are intended to ensure the UK can address “capability gaps”, develop “system resilience and security” through the legacy of the VTF, and “deliver economic growth and the levelling up agenda” with “long term prosperity”.
- Create a National Vaccines Agency.
- Establish a National Centre for Formulation and Delivery to bring together capabilities across vaccine formulation, delivery, process development, and scale-up.
- Clinical trial capability
- Formalise a network between partner organisations to support research and development in clinical immunology, to support increased rich immunological data generation.
- Launch a Human Challenge Study Centre of Excellence to further the UK’s clinical trial capability for respiratory infections and disease.
- Expand the UK vaccine registry, refine the registry by enabling the linking of NHS datasets of consenting individuals to the vaccine register, maintain active communications with registrants and the public, and enhance researcher access.
- Manufacturing capability, responsiveness, and breadth
- The UK should invest in plant-based manufacture of protein antigens to quickly and reliably generate the protein for protein-subunit based adjuvanted vaccines.
- Explore potential opportunities to partner with the most promising mRNA-based companies, academics, and others to provide state-of-the-art mRNA capability to address future pandemics.
- Establishing bulk antibody manufacturing capability to ensure capacity to manufacture sufficient neutralising antibodies to meet needs of UK’s immunosuppressed population and frontline workers.
- Assessing the UK’s vaccines supply chain capability and building a mechanism which monitors and quality assures the resilience of global supply chains.
- Explore potential arrangements with UK based sterile manufacture facilities (CDMOs or pharmaceutical companies) who could provide surge capacity to fill and finish vaccines.
- Develop a strategy to secure the supply of adjuvants.
- Launch a Future Vaccines Fund within UKRI/funded by private sector to advance innovation and support the research of novel formulations and formats.
- International engagement and collaboration
- Use the G7 chairman role to coordinate R&D funding into improved vaccine formats, promote expansion of global manufacturing capability, establish effective long-term information sharing, and encourage streamlining of global regulatory processes.
- Establish COVAX as an international multilateral organisation for future pandemic preparedness.
- Increase the proportion of STEM graduates in the civil service to 50%; develop closer ongoing industry links to improve industrial understanding.
Do you agree with the recommendations? Would they apply in your country as well or do you identify other areas for development? To join discussions on vaccine development, pandemic preparedness and response, and health security, don’t forget to get your tickets to the Congress in Washington this April here, and subscribe for more insights here.
by Charlotte Kilpatrick | Jan 18, 2024 | Technology |
A review in Current Opinion in Chemical Engineering in 2024 highlights how model-based approaches are critical in “accelerating vaccine manufacturing process development”, with the authors emphasising the “significance” of an integrated modelling platform for vaccine manufacturing.
“Vaccine administration is widely recognised as one of the most valuable healthcare interventions for routine immunisation and outbreaks management.”
The importance of developing “efficient and effective pharmaceutical manufacturing processes” was “underscored” by the COVID-19 pandemic as we became more acutely aware of the need for “affordable” vaccines that are available at scale and accessible in as little time as possible.
Continued challenges
The authors recognise that “remarkable advancements” in vaccine discovery science have been made but suggest that the “task of effectively scaling up laboratory-based processes for commercial manufacturing” poses a continued, significant challenge.
“The manufacturing process plays a crucial role in preserving the essential properties identified during vaccine discovery, enabling the production of substantial quantities under tightly controlled conditions for clinical trials and subsequent market supply.”
Vaccine production is “lengthy and cost costly” in nature, with process development accounting for up to 30% of the time taken for successful market introduction of a vaccine.
Innovative technology
Regulatory bodies are keen to enhance the efficiency of pharmaceutical manufacturing and have “encouraged the adoption of innovative methodologies” through Process Analytical Technology (PAT) frameworks and implementation of Quality by Design (QbD) principles. These highlight the importance of knowledge-based tools that “enable manufacturers to better understand, predict, and assure the quality of their products”.
Although model-based approaches have been “widely applied in diverse biomanufacturing domains” for enhanced production efficiency, vaccine biomanufacturing has “not kept pace”. The paper suggests that this is partly attributable to the “ever-evolving landscape” of vaccine types. Furthermore, regulatory concerns “contribute to this constraint”.
Therefore, the authors present an “overview of recent advances in model-based approaches for the purpose of improving process development”, giving an “outlook” on how an integrated model-based approach could influence vaccine manufacturing in the future.
Why incorporate modelling?
The paper identifies “several distinct advantages” to modelling in the context of process development. For example, it offers a “robust framework for understanding the underlying mechanisms of the process”. It can also be a “valuable aid” in the planning and designing of experimental setups and in the evaluation of value propositions and associated risks of new products and processes. Validated models can be applied to the development of advanced control strategies in later stages, and models have recently become popular for the prediction of environmental impacts of processes.
“Models have far-reaching implications beyond process development, particularly in the manufacturing stage. They are the key elements of digital twin and real-time model-based control strategies and can significantly improve the efficiency of manufacturing processes when integrated with real-time data.”
Modelling approaches range from the mechanistic to the empirical, data-driven to hybrid. The latter has emerged as an “effective approach” that combines the “predictive capabilities of mechanistic models” with the “efficiency of data-driven models”.
“This integration allows for minimising the amount of data needed for model development while ensuring the inclusion of physical relevance to key processes.”
A case study in integration
“To achieve an integrated model, a systematic and holistic approach is necessary for harmonisation of the unit operations. This includes interface compatibility, availability and robustness of parameter outputs and inputs, production scales, as well as modes of operations.”
Indeed, the authors state that “failure to couple the unit operations together in a simulation model” is a significant risk in bioprocess modelling. Therefore, it is “essential to comprehensively assess the issues related to heterogeneity, inconsistency, and varying model accuracy across unit processes.” A presented case study is the Inno4Vac project (Innovations to accelerate vaccine development and manufacture).
A key focus of the project is subtopic 4 (ST4), which considers the establishment of a modular open-source computational platform for in silico modelling of protein subunit vaccine biomanufacturing and stability testing. ST4 comprises 5 work packages (WPs) in pursuit of the following objectives:
- WP16: develop stability prediction models for vaccine manufacturing using linear and nonlinear equations and integrate them into a global biomanufacturing platform.
- WP17: establish a cloud-based platform to assess the performance and robustness of biomanufacturing processes, with a specific emphasis on scaling up and down in the production of vaccines using E.coli.
- WP18: create digital twins for key purification units, apply advanced in silico analysis and design tools, and enable real-time control to optimise downstream processing, especially for scale changes.
- WP19: validate the predictive capabilities of in silico models for vaccine stability, unit operations in protein subunit vaccine manufacturing, and control modules developed in WP18.
- WP20: initiate a regulatory dialogue to engage with authorities, paving the way for the future inclusion of predictive modelling in chemistry, manufacturing, and control (CMC) dossiers for vaccines.
The authors conclude that model-based approaches offer “significant opportunities for enhancing vaccine production” but highlight the value of developing an integrated modelling platform for biopharmaceutical manufacturing as exemplified by Inno4Vac.
Do you use modelling in your work, or did you find the publication a helpful insight into how model-based approaches could be implemented in vaccine development? For more on improving and invigorating vaccine manufacturing processes, do join us at the Congress in Washington this April or subscribe to our newsletters here.
