The evolution of the SARS-COV-2 virus is a stark reminder that research and innovation must continue (Step #5)

Developing COVID-19 vaccines in less than a year was a monumental achievement – but to improve the efficacy, manufacture and distribution of vaccines and combat emerging variants, governments, regulators and research scientists must work together to drive further innovation.

Imagine if scientists invented a COVID-19 vaccine that can be given orally, without the need of a cold chain. Or a simple COVID-19 pill to take as soon as the first symptoms appear. Or imagine future generations facing a pandemic and a vaccine or cure can be developed within 100 days. That might seem far-fetched, but these are things that the biopharmaceutical industry can and should strive for. This is what innovation is about – making the impossible possible.

Without a doubt, developing safe and effective vaccines for the SARS-COV-2 coronavirus was an extraordinary scientific feat. Less than a year after COVID-19 was declared a pandemic, the world has not one, but a range of vaccines approved for emergency use. But biopharmaceutical companies, which are part of a large innovative ecosystem of academics, biotech, generic companies, suppliers of ingredients and contract manufacturers, cannot rest on their laurels.

We should be extremely relieved that, within months of the pandemic being declared, we were able to start building an arsenal of therapies and vaccines. We have seen treatments that have been around for decades (dexamethasone), as well as others that were initially developed to treat the Ebola virus (Remdesivir) or arthritis (Actemra), bring hope to people who have been struck down by COVID-19. In parallel, there are other avenues being explored with monoclonal antibody cocktails, new antivirals and anti-inflammatory antibodies.

There have also been some amazing scientific breakthroughs using new technologies, such as mRNA, applied for the first time to vaccines, protecting the lives of millions. At the same time, we have seen setbacks and companies returning to the drawing board. As the virus continues to evolve, companies continue to pursue their R&D efforts to broaden our set of solutions.

A vibrant vaccines pipeline to keep ahead of the coronavirus

During the past year, no opportunities to move quickly have been missed. But no corners have been cut in making sure the vaccines meet the same rigorous standards as any other biological product. Today, scientists continue to monitor all approved vaccines for safety, and candidate vaccines are being tested through robust clinical trials. Some of these trials are now focussed on specific groups, such as pregnant women or children. For example, Johnson & Johnson plans to begin a study of its single-dose COVID-19 vaccine in children as young as 12 years old by this fall. This will be particularly important as we seek to understand the impact of long COVID on populations, including children, and if they need vaccine protection[1].

Also, we do not know yet how long immunity to the virus lasts, or how effective each vaccine will be against new variants as they emerge. It is important that scientific research and clinical trials continue at pace.

According to the WHO, there are more than 100 candidate vaccines in development. Hopefully, new vaccines in the pipeline, such as the ones from Novovax, Sanofi Pasteur and GSK, or Medicago and GSK, will prove to work.

This ongoing drive for innovation is essential in the fight against COVID-19 and will help:

  • Boost immunity: Because both collective and individual immunity to viruses generally weakens over time, booster vaccine shots will play an important role in future immunization strategies.
  • Stay ahead of new variants: Viruses also naturally mutate over time, leading to variants against which current vaccines may prove less effective. Both completely new vaccines and booster shots of existing vaccines are now being developed to combat emerging variants. For example, Pfizer and BioNTech are preparing a booster shot specifically to target the highly transmissible delta variant. Moderna is testing whether booster shots can be administered using smaller dosage levels, which would make production both faster and more cost-effective. AstraZeneca announced that the first participants across the UK, South Africa, Brazil and Poland, were vaccinated in a clinical trial to test their updated COVID-19 vaccines for emerging variants[2]. Most vaccine manufacturers expect to have a newly developed booster vaccine ready by the end of 2021.
  • Target different variants or diseases: Researchers are also investigating the best way to administer multiple vaccines within a single dose. Pfizer, for example, is exploring a co-administered vaccine that could potentially protect older adults against COVID-19 and pneumonia at the same time[3]. Novavax has announced that its co-administered vaccine, offering protection against COVID-19 and flu, demonstrated positive immune responses in a preclinical study[4]. In a similar way, new COVID-19 vaccines could offer protection against multiple SARS-COV-2 variants within a single, co-administered dose.
  • Improve manufacture and delivery: Scientific innovation is not limited to the development of vaccines themselves. New ideas are needed to drive efficiency in manufacturing to compress delivery timelines. Scientific innovation can also make storage and supply cheaper and more efficient. For example, Pfizer and BioNTech are trialling a freeze-dried version of their SARS-COV-2 vaccine that can be stored at room temperature in solid form[5]. These innovations would create significant logistical and economic benefits as vaccines are distributed to populations around the world.

We should not underestimate the amount of research that goes into discovering treatments for COVID-19. Developing effective treatments for COVID will also be crucial to stop the virus in its tracks and lower the risk of hospitals and intensive care units becoming overwhelmed.

Today’s breakthroughs are thanks to years of fostering and enabling innovation

Together with the broader scientific community, the biopharmaceutical industry did not miss a beat in looking to innovation for a solution to COVID-19, and, thankfully, it already had many of the building blocks needed to respond. Recent successes in tackling the pandemic are not one-offs: they come from a long-standing commitment to life-changing innovation, and decades-long investments into cutting-edge medical technologies enabling us to respond swiftly to this crisis.

To continue with such pioneering and wide-ranging vaccine and treatment programs requires the certainty provided to researchers through a clear and consistent framework of public policy and regulation. Intellectual Property (IP) incentives for those spearheading and investing in medical research is also key and will help to cut vaccine development times for COVID-19 while encouraging a speedier response to future pandemics.

IP is also the underlying enabler that has allowed vaccine manufacturers to establish more than 300 collaborations with trusted partners to produce COVID-19 vaccines in historic quantities. Similarly, with treatments, voluntary licenses that depend on the framework provided by IP have been set up with multiple manufacturers around the globe, giving them, in many cases, royalty-free, long-term licenses to manufacture COVID-19 treatments and create supply for both low- and high-income countries.

Sharing samples and data on pathogens

Vaccine developers and the broader scientific community rely on the fast and effective sharing of harmful pathogens and associated information. The first successful vaccines against COVID-19, approved within 326 days from the moment the threat was first identified, could not have been developed with such unprecedented speed had the disease epidemiology of SARS-COV-2 not been made quickly available to everyone trying to conduct research. Indeed, it took little more than a week from the first report of the COVID-19 pandemic for the WHO to confirm the existence of the new coronavirus and for Chinese scientists to publish its genetic sequence.

The COVID-19 pandemic has demonstrated that pathogens know no borders and pose a common global threat to all countries and to all people around the world. When fighting infectious diseases, we need to share pathogens and their genetic information quickly to scientists around the world. This is critical because:

  • Diseases need to be tracked, new variants need to be identified and we need to predict how diseases spread;
  • Scientists and other experts around the world need to start working together to rapidly develop medical countermeasures such as vaccines, medicines and diagnostics.

Only through the swift and comprehensive sharing of information about the pathogen can scientists around the world ensure that vaccines and treatments are well-matched to the latest variants and are developed, manufactured and supplied in the most effective way possible.

Looking ahead to get better prepared for future pandemics

The world is still grappling with COVID-19, but we also need to look ahead at how we can all be better prepared for the future. We learned and are still learning a lot from our successes and failures. However, much we would like to think we are over the worse, there will still be challenges along the way. One thing is for sure, the biopharmaceutical industry is committed to playing its part to help the world through this pandemic and it will, of course, step up to respond to future pandemics.

In June, we announced our support for the goals of the “100 Day Mission” set by stakeholders, including the G7 and CEPI, to develop a plan to deploy high-quality diagnostics, therapeutics, vaccines and treatments in just 100 days after a new pandemic threat is identified. Slashing the time to 100 days to develop and deploy new countermeasures for future pandemic threats is a very ambitious target. But everything from Polio to HIV to Ebola to COVID-19 seemed at times unbeatable. But science and innovation always find a way to do what was once impossible.

[1] https://www.jnj.com/johnson-johnson-expands-phase-2a-clinical-trial-of-covid-19-vaccine-candidate-to-include-adolescents

[2] https://www.astrazeneca.com/media-centre/press-releases/2021/first-covid-19-variant-vaccine-azd2816-phase-ii-iii-trial-participants-vaccinated.html

[3] https://www.pfizer.com/news/press-release/press-release-detail/pfizer-initiates-study-exploring-coadministration-its-20

[4] https://www.medrxiv.org/content/10.1101/2021.06.09.21258556v1.full

[5] https://www.clinicaltrials.gov/ct2/show/study/NCT04816669?term=Pfizer&cond=SARS-CoV-2&draw=2

Enabling the next generation of African Health Leaders for the road ahead

At this year’s regional World Health Summit in Uganda, we had the pleasure of showcasing the research fellows that IFPMA has been supporting as part of the Chatham House African Public Health Leaders fellowship program since 2016 in an event titled “Will COVID-19 dictate a new paradigm in Africa?” This event was a unique opportunity to get a ‘temperature check’ from public health leaders on the ground about the pandemic’s potential to transform the future of health in Africa. Six fellows, who hold key positions in national disease control programs, universities and the media, provided valuable insights into how the current pandemic will impact the future of Africa’s health systems, based on experiences from their countries and areas of work.

Key takeaways from the event

  • Home-grown research and data collection is needed to ensure evidence-based prioritization of the most pressing health challenges.
  • Self-reliance and finding African solutions for African problems is key.
  • Political will must drive investment in public health and health security.
  • Leadership at a continental level, including by the African Union and Africa Centers for Disease Control and Prevention (CDC), is necessary to coordinate the response to present and future pandemics.
  • All public health challenges, such as noncommunicable disease (NCD) control and the fight against antimicrobial resistance (AMR), require consideration.

Hearing from African rising stars in public health

While the COVID-19 pandemic is far from over and continues to take a heavy toll, history has shown us that out of great calamities, great successes can arise. However, for this to happen, it is important to prioritize the most pressing health challenges, and this can only be achieved by linking local realities to the wider African picture through home-grown research and data collection. This includes setting up the right structures and networks to enable messages to get through from all parts of society, including marginalized, vulnerable and front-line community voices.

From a macro perspective, the pandemic has clearly shown us that we need to rethink our public health order. For Abdulaziz Mohammed, Head of Disease Control and Prevention at Africa CDC, the continent needs to give more attention to health, including through strengthening of national public health institutions, development of health workforce and respectful partnerships with development partners. Regarding a step-up of financial commitments, it will be important to strike while the iron is hot. As highlighted by Vivianne Ihekweazu, Managing Director at Nigeria Health Watch, historically African countries have not dedicated sufficient share of their budgets on health, despite the 15% pledged in the Abuja Declaration, which was agreed in 2001 and aimed to strengthen Africa’s health systems and ensure their preparedness for disease outbreaks. That is why a paradigm shift needs to occur whereby increasing health budgets should be seen not as a cost but as an investment. Ama Pokuaa Fenny, Senior Research Fellow at University of Ghana Legon, noted how COVID-19 has tested Universal Health Care and the value of leaving no one behind. It also is important to remember that investing in health systems makes sense not only from an inclusion and pandemic preparedness point of view, but also from an economic growth and resilience perspective.

Importantly, and to be better prepared for the next crisis, there is a strong need for local African manufacturing of therapeutics, vaccines and diagnostics. As mentioned in my previous blog on expanding manufacturing in Africa, this will be a marathon and not a sprint, and goes hand in hand with other important steps, such as creating a regulatory environment that encourages investments, developing technical skills locally and focusing on manufacturing capacity at the African level.

Reshaping health frameworks requires a sustained effort that encompasses all key health challenges. For example, as mentioned by Brian Kermu Ngwatu, Infectious Disease Specialist and Senior Clinical Advisor at the Clinton Health Access Initiative’s Clinical Sciences Team, COVID-19 has compromised sustained investment in research and the multifaceted fight against AMR. That is why it is important to ensure a true health mind shift, not just a temporary focus of attention and resources. For Valerian Mwenda, Medical Epidemiologist at the National Cancer Control Program in Kenya, healthcare is not only a scientific construct but a social one too. Changing the paradigm is about doctors, drugs and vaccines, and equally about a behavioral change, and this takes time to achieve.

Young African public health leaders hold the promise of a better future

While there is much work to do and there is a long road ahead, I see that there is also a lot of hope for the future after listening to the Chatham House Africa Public Health Leaders fellows. The new public health generation has experienced a unique global health emergency and knows well the obstacles that must be overcome. This generation is more educated, connected and international than ever before. It is also eager to contribute creative new ideas to the global health conversation.

With regards to the question “Will COVID-19 dictate a new paradigm in Africa?”, I believe the answer is a clear “yes.” A key step will be having strong leadership from the next generation of public health leaders in Africa. That is why it is so important to build the capacities of promising public health specialists on the ground and to enable their full potential through programs like the African Public Health Leaders fellowship.

We are still at the beginning, but there are some positive signals in Africa, such as the recently announced collaboration between Johnson & Johnson, Aspen, the World Bank and government agencies to produce COVID-19 vaccines in South Africa. Furthermore, we welcome progress on the common vision and strategy of the African Medicines Agency, which will serve as a key institution helping to strengthen healthcare systems in Africa. Despite the pandemic and other looming health crises, hearing from the six fellows gives me hope for the future and reason to believe the next generation is ready to face the challenges ahead. As Adesola Yinka-Ogunleye, Epidemiologist the Nigerian Centre for Disease Control, said, the COVID-19 pandemic has dictated the need for a new health paradigm not only for Africa but for the world, and there will be lessons to be learned for all of us along the way.

Each and every country faces unique challenges in rolling out COVID-19 vaccination (Step #4)

We have a realistic hope of producing 11 billion COVID-19 vaccines by the end of 2021 to vaccinate the world’s whole adult population. With increased dose sharing and urgent measures to ensure vaccine equity through COVAX and other bilateral agreements, we would like to see many more vaccines reaching all four corners of the world in the second half of 2021.

So that every dose received is administered quickly and effectively, country readiness is a key pillar of the global strategy for COVID-19 vaccination. Rolling out mass vaccination campaigns presents logistical challenges for any country. Low- and middle-income countries (LMIC) face particular challenges. Many LMICs have well established childhood vaccine delivery, but not all countries are as well equipped to target large numbers of adults and reach them several times, as most of the COVID-19 vaccines require two doses.

Country readiness to absorb COVID-19 vaccines deliveries is vital

National COVID-19 vaccination programs require detailed planning and adequate resourcing. As vaccine deliveries ramp up in LMICs, with deliveries increasing 3-6 times in the 4th quarter from current levels, countries must be ready to roll out vaccination programs as soon as doses are delivered. According to WHO AFRO, 49 African countries have been recently notified of the allocations they will receive[1]. Each country has an absorption capability that will dictate how they can best use the large COVID-19 vaccine deliveries expected in the coming weeks. Governments should use this time to prepare for the roll-out, conduct reviews and focus on:

  • Developing national vaccination plans
  • Establishing regulatory vaccine approval and vaccine safety systems
  • Building vaccine distribution infrastructure on the ground, including cold chain capacities
  • Training of staff involved in deployment and delivery of vaccines
  • Strengthening data collection, reporting and tracking systems
  • Addressing hesitancy issues by planning public health campaigns to generate trust and demand for COVID-19 vaccines.

Vaccine deliveries scale-up

Every country must overcome distribution challenges but LMICs will come under increasing pressure over the coming months to administer all the doses that have been allocated to them and to limit the risk of dose wastage. COVAX aims to deliver 1.9 billion doses to 91 countries in Q4 2021, including 520 million COVID-19 vaccine doses to Africa in 2021, and nearly 850 million by the end of the first quarter of 2022. Most of these doses will be delivered from September 2021 onwards.

As vaccine deliveries ramp up, distribution bottlenecks could worsen and risk more doses becoming expired. In the same way that vaccine manufacture has been accelerated, more can be done to provide operational funding and technical support to bolster LMIC programs. To help prepare LMICs for this acceleration, an additional US$ 775 million of funding for COVAX vaccine delivery has recently been approved[2] in complement of delivery funding from USAID and the Asian Development Bank. But the clock is ticking and serious gaps in country readiness remain.

Logistical challenge of multiple COVID-19 vaccines

Today, we are lucky to have several approved COVID-19 vaccines, but this adds complexity as well. Countries will receive supply of different vaccine products, from Pfizer/BioNTech, Johnson & Johnson, AstraZeneca/SII, Moderna, Novavax, Sinovac, and Sinopharm, constituting an additional complexity for healthcare workers and programs. Healthcare professionals need product specific training and guidance, delivery strategies need to fit product specificities, and each vaccine requires different cold chain capacities, as well as track and trace processes.

Confidence in COVID-19 vaccines: Winning over hearts and minds

Additionally, factors leading to delays include hesitancy among the population to get the vaccine. Misinformation campaigns present another threat that could undermine efforts to get the pandemic under control.

To build confidence and understanding, governments, community-based organizations, healthcare providers and vaccine manufacturers need to work together. Health campaigns have a role to play in ensuring quality information reaches people to generate public confidence, trust and demand for COVID-19 vaccines. Vaccine hesitancy has been a concern of our industry for many years and we take our efforts to address vaccine hesitancy just as seriously as we do our R&D and manufacturing work. Our industry embraces the highest regulatory standards and works with health authorities to strengthen pharmacovigilance systems, develop the capabilities to monitor and investigate potential adverse events quickly, and to communicate and address public concerns proactively.

Success relies on whole health system approaches

According to Marian Wentworth, President and Chief Executive Officer of Management Sciences for Health (MSH), an organization that helps build resilient and sustainable health systems, with extensive experience in some of the globe’s most challenging environments, many vaccine distribution challenges could be overcome with technologies that facilitate cold supply chain monitoring, patient records and collection of information, and last mile delivery logistics[3]. Innovative technology and collaborative partnerships will be critical to build resilient health systems that are able to deliver immunization services across the life span, both during and outside of pandemics.

In April 2021, WHO warned that COVID-19 continues to disrupt essential health services in 90% of countries. The COVID-19 pandemic poses serious challenges to many countries, including disrupting routine immunization programs. Twenty-three million children missed out on basic vaccines through routine immunization services in 2020 – 3.7 million more than in 2019 – according to data published recently by WHO and UNICEF.

We all need to work together to help countries strengthen their COVID-19 vaccine rollout, and get routine immunization programs and other essential health services back on track.

[1] https://www.afro.who.int/news/africas-covid-19-surge-tops-second-wave-peak-vaccine-deliveries-pick

[2] https://www.gavi.org/news/media-room/gavi-board-strengthens-commitment-reaching-most-vulnerable-through-routine

[3] https://nextbillion.net/covid19-vaccine-distribution-partnerships-technology-supply-chains/

Why we must remove barriers to trade to achieve vaccine equity (Step #3)

To put an end to the pandemic, industry was tasked with manufacturing and supplying billions of COVID-19 vaccines, starting from zero. This monumental task is on its way to being achieved, with 11 billion doses forecast for the end of 2021[1]—enough for the world’s adult population, according to the World Bank. However, trade restrictions, amongst other hurdles, are holding up both upstream and downstream supply, presenting a significant challenge to achieve vaccine equity.

The manufacture of 11 billion doses of COVID-19 vaccines by the end of 2021, along with the yearly production of 5 billion doses for other vaccines for diseases, represents a trebling of vaccine production within a year. Such scale impacts the availability of raw materials, skilled workers and vaccines supply. This increase in global traffic leads to significant and inevitable strain on the global vaccine manufacturing supply chain and any glitch or hold-up in the chain can set back efforts to optimize this vital scale up. A delay in a single ingredient can stall production, which in turn leads to delay in supply.

The WTO and its member states have recognized and acknowledged this bottleneck. Dr. Ngozi Okonjo-Iweala, Director-General of the World Trade Organization (WTO), recently noted that the number of trade restrictions related to medical supplies used against COVID-19 has risen to 53 trade restrictions in 2021 alone. This year has also seen trade restrictions on the distribution of vaccines. To address these concerns, a number of Member States have proposed a draft declaration on trade and health.[2]

To meet the unprecedented demand, industry has entered into more than 300 manufacturing deals, 220 of which involve technology transfer. Skilled workers are needed to transfer the technology and train manufacturers on quality and safety, and their availability is also severely impacted by trade restrictions. Despite the industry’s best efforts and robust contingency plans, these bottlenecks continue to disrupt production and supply of COVID-19 vaccines.

Therefore, as part of our Five Steps to achieve vaccine equity, we are calling on governments for trade restrictions to be eliminated for the uninterrupted movement of critical supplies, vaccines and skilled workers to produce enough COVID-19 doses for the world to end the pandemic.

Trade Interdependencies: Goods and Services

Vaccine production is highly complex, specialized and dependent on the global supply chain, with swift transit of goods, services and personnel.

The complexity of a single vaccine means scores of components are needed from suppliers across the globe. For example, the Johnson & Johnson vaccine contains 180 components manufactured at 67 sites in 12 countries; the Pfizer-BioNTech vaccine requires 280 components, relies on 86 suppliers located in 19 countries and is produced in just three manufacturing plants; the Moderna vaccine has a similar number.

Lipids are important for the delivery of mRNA vaccines, which, prior to the pandemic, were not required on such a scale. Different types of equipment are needed for vaccine production in manufacturing and storage, such as bioreactors and fridges/freezers. Other medical goods are required for manufacturing, packaging, storage and the administering of vaccines, such as vials, cold boxes, syringes, and needles. Currently, six critical input supplies are facing or likely to face shortages: bioreactor bags, single-use assemblies, filters, cell culture media, lipids, vials and stoppers.

To further complicate matters, no one manufacture or production line is the same as that of another vaccine. Airfinity, a life-science analytics company that provides real time information on vaccine production, has mapped 83 sites producing vaccine drug substances across the world[2], each with their own process.

Despite these challenges and this complexity, barriers to trade and tariffs on medical products are still imposed by many countries. One-fifth of countries have positive duties on vaccines, with 8% having a duty equal to or greater than 5%. Eliminating or reducing tariffs on medical goods and inputs will help expedite production.

Today, we run the risk of a single ingredient being held up at a border, leading to the halting of the entire manufacturing process. Restrictions on the upstream supply chain are leading to shortages of raw materials. Many of these essential components and those on the downstream supply chain are impacting distribution, resulting in doses being wasted and disposed of and prolonging the pandemic. This is something the world cannot afford.

Governments need to address and eliminate unnecessary supply chain barriers and export restrictions on both intermediate and final goods so we can get vaccines to people, curb excessive stockpiling and end this pandemic.

And where export restrictions are critical and need to be applied, they should be targeted, proportional, transparent and temporary. We echo the statement by Dr. Ngozi calling on the G20 leaders to “do more,” from donating more COVID-19 vaccines to removing trade restrictions that affect the vaccine supply chain.

Trade Interdependencies: Personnel

Given the complexity of the vaccine manufacturing process, a skilled workforce is the lifeblood of the process. If trained workers are not conducting quality checks and scientific equations, the raw materials being used will go to waste and production will have to restart.

A skilled workforce is also vital for successful technology transfer between vaccine makers. Not only are they involved in the production process, they also train the licensees to manufacture. Training for technology transfer is time intensive. It helps if the licensee can absorb the technology. For example, the Moderna facility in Switzerland (Lonza site) was unable to be up and running at an earlier date because the facility could not hire enough skilled workforce.

Needless to say, a skilled workforce is an invaluable component of the entire vaccine manufacturing process and is already stretched due to the pandemic. This workforce needs to be efficiently and effectively used. Today, the top 10 vaccine manufacturers have more than 5000 vacancies for skilled workers[3]. Prioritizing the movement of skilled workers across borders is crucial to ensure training for tech transfer takes place and large manufacturing plants have the required workforce to conduct quality and safety checks.

Vaccine Protectionism

The barriers to trade are further complicated when governments put policies in place to safeguard their own vaccine supplies for their population. These policies can lead to supplies being disposed of unused, while other countries are requesting that very supply—this needs to be revaluated. The measures also put unnecessary pressure on the supply chain,  the impact of which has been acutely felt during the pandemic, as noted by World Health Organization (WHO) and WTO.

For example, the US employed export controls under the Defense Production Act (DPA) to prevent companies from exporting vaccine doses or ingredients without federal government authorisation. This decision was misguided and led to hurdles in production, as noted above. A similar restriction was placed by India, impacting supply to COVAX.

We have also seen national legislations restrict exports of raw materials. According to Airfinity, 39% of bioreactors suppliers and 37% of lipid suppliers are headquartered in the US. Legislation like the DPA controls the export of these raw materials, which leads to production lines being held up, impacting overall supply. This issue became so dire that it led to the CEO of the Serum Institute of India appealing to the US President on Twitter to lift the embargo on raw material exports out of the US, “if we are to truly unite in beating this virus.”  Rajinder Suri, CEO of the Developing Countries Vaccine Manufacturers Network (DCVMN), stressed that the export restrictions have implications for the COVID-19 vaccine rollout across the world.

It was a welcome change in June this year when countries, including the US and EU Member States, agreed to dose sharing, and we hope that India can start exporting by October. Nevertheless, more can be done, as highlighted by WHO and WTO. Dr. Ngozi called for the G20 to donate at least two to three billion more doses to countries with high disease burdens.

Call to Action

There is growing recognition that the immediate needs of the biopharmaceutical and biotech industry to achieve vaccine equity are hampered by shortages of raw materials and restrictions on distrubution through export bans.

The WTO and its members have an important role to play to eliminate trade restrictions, to adopt policies that expedite the cross-border supply of inputs and finished vaccines, and to allow the movement of skilled workforce.

On 31 June 2021, 23 member states communicated a draft text for a Declaration on Trade and Health to be announced at the WTO Ministerial Conference in November. It includes reviewing and removing export restrictions with efforts to be made to remove or reduce tariffs.

These calls now need to become actions. Viruses ignore borders and supply chains are global. Only by removing trade restrictions and working together to streamline border processes do we stand a chance of ending the pandemic and achieving vaccine equity.

[1] Airfinity Presentation at WTO COVID-19 Vaccine Supply Chain and Regulatory Transparency Technical Symposium on 29 June 2021: 

[2] https://docs.wto.org/dol2fe/Pages/SS/directdoc.aspx?filename=q:/Jobs/GC/251R3.pdf&Open=True

[3] https://www.wsj.com/articles/covid-19-vaccines-are-in-high-demand-but-thousands-more-workers-are-needed-to-make-them-11609764172

COVID-19 vaccines: Meeting the world’s need (Step #2)

Boosting production of COVID-19 vaccines is key to ensuring there are enough doses for all populations most at risk. But manufacturing COVID-19 vaccines at the volumes the world needs is a colossal challenge and scarcity of raw materials and trade barriers could upset estimates that 11 billion doses – enough for the world’s adult population – can be produced by the end of 2021.

To achieve vaccine equity, vaccine manufacturing yields must be optimized and bottlenecks in the supply chain either pre-empted or tackled urgently.

Not Business as Usual

Scaling up manufacturing has been a daunting task, but thanks to steps taken in the first months of the pandemic, production for COVID-19 vaccines has increased from zero to 3 billion doses in the past six months since the first approval of a COVID-19 vaccine.

It has required an unprecedented effort and collaborations across the pharmaceutical and vaccines industries both in developed and developing countries. The good news is that we are now on track to more than double pre-pandemic global capacity for all vaccines and achieve 11 billion doses of COVID-19 vaccines by the end of the year.

But production needs to accelerate and be optimized. At present it can take between 90 to 120 days to manufacture a single batch of COVID-19 vaccine whether mRNA, viral vector or recombinant protein. Companies are working to reduce lead times as much as possible. For example, Pfizer-BioNTech launched ‘Project Light Speed’ to shorten production time of its mRNA vaccine from 110 to 60 days.

Successful Collaborations

From the onset the industry knew it would need to scale up rapidly and vaccine makers quickly began scouring the world to find suitable and trusted partners with proven track records and the “best fit” for assured quality, efficiency and scale of production. Today, there are more than 300 partnerships and collaborations that are working with vaccine makers towards this historic effort.

What has been achieved so far is unprecedented and licensing agreements and technology transfers have been fundamental in scaling up. Efforts to create globally-optimized networks of suppliers and producers are paying off.

We have seen biotechs, pharmaceutical companies, and contract manufacturing organizations (CMOs) from developed and developing countries come together to increase capacity. Vaccine innovators have built ties with hundreds of companies, the best known being theSerum Institute of India, Bharat Biotech, Aspen Pharma and also Biological E. Whether the collaborations involve helping make the vaccine from scratch or contributing to the final stages, such as “fill and finish” the vaccine innovator will help by transferring its know-how and technology, to ensure partners can reach the levels of quality needed, as well as the optimum levels of output.

This sharing of knowledge does take time to get it right. For example, in addition to its existing manufacturing capacities, Johnson & Johnson has entered into multiple agreements to expand manufacturing capability for drug substance, drug product, or packaging, with more than 10 manufacturing partners around the world. One of these partners is Aspen Pharma with whom Johnson & Johnson agreed to transfer its technology last year. Their joint efforts will soon be paying off, with the first vials leaving the manufacturing lines in South Africa in the coming weeks. But sometimes, despite everybody’s best efforts, things go wrong. One of Johnson & Johnson’s partners Emergent BioSolutions in the USA was found not to be fully compliant with safety and effectiveness. This resulted in the FDA stepping in and deciding that 75 million doses need to be thrown away.

Many have heard of the licensing agreement AstraZeneca made with the Serum Institute of India last April, but this is not the only collaboration AstraZeneca is involved with. The company has recently announced a technology transfer agreement with Fiocruz in Brazil, which builds substantially on existing fill and finish to allow active pharmaceutical production.

Since IFPMA announced its 5-step plan to urgently improve vaccine equity on 19th May, the already high number of partnerships has further increased from 286 to 307. New tie-ups include AGC Biologics and BioNTech or Moderna and Samsung Biologics and Thermo Fischer Scientific.

Technology transfers are complex in their nature, including the technology itself. Certain external factors play a key role in determining whether a company wishes to engage in a technology transfer within a region. These factors include a transparent and stable legal and policy framework, an innovation ecosystem backed by intellectual property incentives, high technical and regulatory standards, availability of raw materials and trade barriers, to name a few. In addition, it is crucial that the partner being selected is one that has the capacity and capability to absorb the technology, have the necessary skilled worker and the ability to scale up. A proven track record on safety and quality is undeniably a factor where no compromise should be made.

The basis of any technology transfer arrangement is trust and willingness to work together, and we have seen how transfer of know-how can be greatly accelerated.

Challenges Ahead: Shortages of Critical Supplies and Workforce

Despite the best efforts of all those involved in the scaling up of manufacturing, there are numerous challenges that could thwart vaccine production and the first year estimate of 11 billion doses. Raw materials are in short supply and scarcity of critical input supplies, such as bioreactor bags, single-use assemblies, cell culture media, filters, lipids, vials and stoppers is hampering production. A delay in the supply chain of any one of these components can set back production output by weeks if not months.

It is important to stress that these ingredients are also needed for other routine vaccines, such as hepatitis, measles, shingles and biological medicines used in the treatment of cancer. Greater visibility in the supply chain could help avert these bottlenecks.

Also key to continued production is a skilled workforce. Vaccines are complex biological products, and their production and oversight requires a complicated dance of multiple experts in manufacturing, quality, regulation, engineering, and logistics as well as trainers, lab technicians, maintenance crews, scientists, and many more. Pharmaceutical manufacturing teams are currently stretched, and additional specialized technicians are needed to ensure the smooth running of the myriad of production steps and quality checks. As Moderna experienced when Lonza was unable to start production as soon as had been hoped, due to a lack of skilled technicians needed to set up and run production lines.

The World Trade Organization (WTO) and The World Customs Organization (WCO) also have an important role to play to work with governments to eliminate trade barriers to export and to adopt policies that facilitate and expedite the cross-border supply of key raw materials, essential manufacturing materials and vaccines, along with the prioritized movement of skilled workforce needed for COVID-19 vaccine manufacturing.

Speed up Regulatory Processes

Finally, the pandemic has shown that regulatory systems can collaborate and be more agile, and this can help avoid wasting time and resources. Regulatory approvals for COVID-19 vaccines have been facilitated and accelerated, but there is a need to continue to harmonize regulatory standards across countries and speed up requirements to validate processes, approve new manufacturing sites, and avoid redundant local testing that could reduce the remaining shelf life for a vaccine.

In addition, the emergence of variants requires regulatory authorities to react quickly to approve updated vaccines. Solutions to help expedite these approvals include use of reliance, work-sharing, and recognition processes along with digitalization.

Staying Ahead

Industry continues to carry out research to ensure the wheel of innovation continues. We are hopeful that several new vaccines are likely to come to the market in the next few months. Upon regulatory approvals, Novavax remains on track to reach manufacturing capacity of 100 million doses per month by the end of the third quarter and 150 million doses per month by the fourth quarter of 2021.

However, addressing bottlenecks with practical steps must continue. That’s why our 5-steps plan to urgently address vaccine inequity is important. Manufacturers, governments, and non-governmental organizations must work together to take urgent steps to address vaccine inequity, with immediate action on stepping up responsible dose sharing and maximizing production without compromising quality or safety. We must remain ahead of the virus and collaboration is the only way out of the pandemic.

Harmonizing regulatory requirements to accelerate the supply of vaccines

This blog was originally published on the Media Planet Campaign Value of Vaccines on 25 June 2021.

Over the past few decades, the global regulatory environment has become more stringent and demanding to consistently guarantee the quality, safety and efficacy of medicines and vaccines.

The increase in requirements by regulatory authorities has not been implemented equally across the world. Nowadays, we have a high heterogeneity in terms of dossier review, approval processes and timelines, with each country having specific data requirements and processes which often differ between countries. As such, it is virtually impossible for every country in the world to have access to medicines and vaccines at the same time.

Regulatory requirements under COVID-19

Unfortunately, while vaccines are widely recognised as the most important tool to exit the COVID-19 pandemic, regulatory requirements have not been harmonised and simplified across the world to expedite access.

It has highlighted some weaknesses in the system, more precisely in the regulatory management for manufacturing and controls. For instance, the processes to validate, approve and recognise new manufacturing facilities, an essential step in scaling up vaccine production, are still not agile enough.

 

There are multiple changes in process that can happen after a vaccine is first approved, such as new types of fridges used or tests performed. We can see dozens of changes each year, which you need to multiply by the number of countries where the vaccines are approved, resulting in thousands of variation dossiers. This will become even more significant for COVID-19 vaccines as data will change at a faster pace than for regular vaccines.

Several countries perform testing on vaccine batches which is redundant and time-consuming, and not always using the same test method and applying the same specifications. Initial COVID-19 vaccine batches have limited expiration dates. Therefore, redundant local testing reduces the remaining shelf life for a vaccine, potentially resulting in discarding expired doses.

The emergence of variants has led to the need to react quickly by developing, manufacturing, and approving new vaccines against those variants, for whom most of the above challenges will also apply.

The way forward

There are four areas which provide solutions for the regulatory concerns, which are:

  1. Science and risk based approaches
  2. Global regulatory harmonisation
  3. Use of reliance, work-sharing, and recognition processes
  4. Digitalisation

These solutions are not new and, whilst this pandemic has witnessed some progress at authority level, a lot needs to be done. Ultimately, quick and widespread access to medicines and vaccines is most important.

Dose sharing is a critical urgent step towards vaccine equity: it needs support to be successful (Step #1)

Step 1 of the biopharmaceuticals 5-step plan to address vaccine equity

A number of countries with access to sufficient doses to vaccinate their own populations have pledged 1 billion doses so far for low- and middle-income (LMIC) countries in 2021 and 2022. We now need to ensure those pledges are realized and vaccines reach those who need them most.

The good news is there are increasingly more doses available. Not least because the global biopharmaceutical industry is on track to produce at 11 billion doses by the end of 2021. If shared equitably, that’s enough to vaccinate most of the world’s entire adult population.

To make sure these vaccines reach the people who need them, collaboration between governments, industry and other stakeholders is needed to plan the orderly distribution of the vaccines – spread out in such a way that countries receive the first shared doses as soon as possible and not all at once at the end of 2021.

The logistics of the vaccine rollout is complex. Let’s not forget, this has never been done before on such a scale. The complexities of delivering to billions of people in urban as well as in more remote settings are manifold, and all against the ticking clock of vaccine shelf life.

Planning

The key to ensuring dose sharing delivers on its promise of equity goes far beyond pledges. It’s about having all the necessary information to understand what needs to be done, by who and when. The sooner there is clarity on when the earmarked doses will be available and where they will make the greatest impact, experts along the whole chain can spring into action.

We need to deliver doses in a reliable and predictable way. We need to track progress to tackle and learn from bottlenecks. We need to work together as one.

Five-Step Plan

We know that action is needed in five areas to advance COVID-19 vaccine equity:

  1. Stepping up dose sharing;
  2. Optimizing production;
  3. Eliminating trade barriers;
  4. Supporting country readiness;
  5. Driving further innovation.

These steps are interdependent: for dose sharing to be successful, we need to progress on all steps at the same time.

So where are we now and what do we know? There is good news as a number of important announcements have been made.

G7 countries have pledged 1 billion doses for poorer countries, primarily through COVAX, with over half of these doses due to be delivered in 2021. Deliveries from France are already underway. The US also announced a donation of 500 million doses of the Pfizer-BioNTech vaccine, provided by Pfizer-BioNTech at a not-for-profit price. In addition, at the recent G20 Global Health Summit, vaccine manufacturers pledged to supply 3.5 billion doses of COVID-19 vaccines in 2021 and 2022 for low and middle income countries at cost or discounted to COVAX and other established mechanisms, in addition to the 800 million doses pledged earlier.

We need to drill down to fully understand how quickly these pledges will be fulfilled and how quickly doses can be rolled out, and get jabs into arms. 515 million doses have been pledged for 2021, and according to the latest forecast they should start becoming available in significant numbers very soon and then to be relatively evenly paced through the year[1]. But we know that the forecast will continue to evolve as we know technical issues, regulatory processes, delivery constrains could have an impact on supply schedules.

All these developments, with hopefully more to come, are encouraging as we work towards global vaccine equity. But there are likely to be bumps in the road, simply because we are all doing something that has never been done before.

Accelerating Roll-Out

Dose sharing remains an extremely complex global undertaking with high stakes. Manufacturers need to accelerate production working with hundreds of partners around the world and dispatch at speed while fulfilling all regulatory and legal requirements. They must maintain a laser-like focus on the supply chain to guarantee the quality and safety of all vaccine batches. Governments need to smooth the path for vaccines to enter their countries, while protecting their citizens. Regulatory bodies need to ensure safety, accountability, and process.

If donated doses are to reach the people they are intended for, government, industry and other stakeholders need to collaborate to address these complex and interconnected challenges.

Addressing Deployment Gaps

Once doses have been donated, if they are to reach populations at risk, relevant organizations and programs need to assure financing and support to governments to enhance their vaccine distribution capacities. The timeline of deliveries should also be informed by the countries’ absorption capabilities. All countries face challenges rolling out massive vaccination campaigns, but LMICs particularly will face an intense pressure over the coming months. So knowledge sharing is vital as those countries that have successfully implemented inoculation programmes have critical know-how and technical support to give.

And the clock is ticking. The more time lost getting the logistics sorted, the greater the risk of doses going to waste. According to WHO AFRO, twenty-three African countries have used less than half of the doses they have received so far. About 1.25 million AstraZeneca doses in 18 countries must be used by the end of August to avoid expiration.

Unfortunately, we see countries having to juggle logistics around thousands of municipalities and local authorities to store and then be ready to administer their doses before they expire. This is why it is important to ensure that the donated doses are spread out over time, on a continued, rolling basis.

It is critical to build capacity to effectively store, distribute, and administer vaccines. And while doses are donated, the rest of the process needs to be budgeted to cover the costs of:

  • Developing national vaccination plans;
  • Establishing regulatory vaccine approval and vaccine safety systems;
  • Building vaccine distribution infrastructure on the ground, including cold chain capacities;
  • Training of staff involved in deployment and delivery of vaccines;
  • Strengthen data collection, reporting and tracking systems;
  • Addressing hesitancy issues by planning public health campaigns to generate trust and demand for COVID-19 vaccines.

Each of these challenges is a pressing problem in itself. Vaccinating the world against a virulent and deadly disease is a colossal global challenge. Yet the 5-steps plan to advance vaccine equity provides a robust framework to help bring the pandemic under control.

[1] COVAX Global Supply Forecast 

COVID-19 and the Path Forward: Learnings Inform Future of Global Collaboration

In light of the recent G7 Summit 2021, where the COVID-19 pandemic was understandably the overarching point of discussions, I was reminded about the key role our industry is playing in this health and economic crisis. This pandemic, the like of which has not been seen in over 100 years, has cost too many lives and put many more at risk.

Yet, the promise of medical innovation brings hope each day. A number of vaccines and treatments are already approved for use in health systems worldwide, and many more are being developed, including antibody treatments from companies like mine, Bristol Myers Squibb, among others. As countries begin to reopen, glimmers of pre-pandemic life appear. Still COVID-19 and its variants continue to affect many, especially those in low- and middle-income countries.

While we have more to do to ensure patients around the world have access to vaccines and treatments, I am encouraged by the progress of our innovation and the speed of our delivery, which is the result of unparalleled, swift collaboration between members of the global biopharmaceutical community, healthcare professionals, governments and health systems. I am hopeful our advancements mean the pandemic’s effects will soon subside in every corner of the globe.

I am also reminded of the importance of organizations like the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) for their ability to convene the world’s best biopharmaceutical innovators and leaders to inform and facilitate global thinking and drive urgent action on how to confront major health issues – from COVID-19 to cancer. Learnings from the past year will help inform the next chapter of close collaboration and medical innovation as we seek to address diseases and conditions for patients across the world.

For example, IFPMA has found success in leading multi-stakeholder approaches to combating COVID-19 and supporting efforts to address non-communicable diseases (NCDs) in low-and middle-income countries (LMICs):

  • As a founding member of the ACT-Accelerator, of which the COVID-19 Vaccine Global Access Facility (COVAX) is a key pillar and driver of research and development, we have learned how to bring together the needed expertise to expedite scaling up manufacturing and the supply chain to unprecedented levels.
  • Via Access Accelerated, a unique cross-industry collaboration of 24 biopharmaceutical companies, including Bristol Myers Squibb, we have delivered results in reducing barriers to prevention, treatment and care for NCDs in LMICs through health systems by strengthening and aligning with Universal Health Coverage objectives and priorities.

These efforts are great examples of how we can take on the complexities of global drug discovery, development and delivery, and collaboratively work across the industry with governments and NGOs, and other key stakeholders to find solutions.

As we look towards the future, the IFPMA and the biopharmaceutical industry are addressing a number of key areas including:

  • COVID-19 with collaborative and proactive efforts which we’ve been tracking against our industry commitments since the beginning of the pandemic[1] and more recently announced five steps to urgently advance vaccine equity.
  • The central role that the biopharmaceutical industry and the innovation eco-system play in tackling any future pandemics, and solutions needed for a more robust global healthcare architecture to better protect and secure societies and health systems.
    • The recent backing of the 100 Days Mission by G7 leaders and biopharmaceutical companies, which aims to ensure diagnostics, therapeutics and vaccines in just 100 days after the next pandemic, is a promising step forward for patient-centred collaboration in this space.
    • As the World Health Organization considers the International Pandemic Treaty, it will be important for leaders to understand the role of our industry as part of its multi-sector preparedness plan.
  • Health systems’ efficiency and sustainability, working to strengthen patient access to healthcare and medicines globally as the economic fallout of COVID-19 continues.
  • Advocating for the drivers of innovation for all medicines, including intellectual property protections, which are essential for continued biopharmaceutical innovation necessary to address current and future unmet medical and health needs.

These issues require smart thinking, multi-disciplinary collaboration, a global mindset and local expertise.

I am proud to represent Bristol Myers Squibb as Council Chair of the IFPMA as I believe it is an essential platform for our industry to work together and speak with one unified voice. Through meaningful partnerships and collaboration with other stakeholders, we can better promote the discovery and development of innovative medicines for patients worldwide and tackle access barriers to healthcare in pursuit of global health equity. Together we do more for patients and society.

[1] IFPMA COVID-19 Information Hub

Ensuring the delivery of vaccines in record time

This oped was originally published on in the Down to Earth (16-30 June 2021 Edition).

Scarcity of raw materials and trade barriers could dent hopes for 10 billion vaccines produced by end of 2021

Back in March 2020, vaccine innovator companies started working on how they would set up manufacturing and the supply chains produce their vaccines candidates once they were approved.  One of the reasons for the speed at which the world has been able to produce COVID-19 vaccines in the billions in a matter of months, was the fact that production and supply teams worked in parallel with the scientists in the labs, not knowing yet whether their vaccine would make it to the finishing line  – something that has never been done on such a scale before.

Their efforts are clear to see. At the end of this month, three billion COVID-19 vaccine doses will have been made by the vaccine manufacturing four powerhouses: China, the European Union, the United States and India.  By the end of 2021, it is estimated that over 10 billion doses will have left the production lines.

As part of the manufacturing preparations, the first of today’s 300 collaborations were being drawn very early on.  Today, cooperation is taking place in many parts of the world: in USA, China, EU and India, but also South Africa, India, Brazil, Argentina, Malaysia, Turkey, Thailand, Egypt, Mexico, Indonesia, Iran. Getting collaborations up and running takes time.  Aspen Pharma in South Africa and Johnson & Johnson agreed to work together in November last year for the fill and finish process to put the vaccines into vials.  Aspen plans to have the vials leaving the manufacturing lines at the end of June.

Another early preoccupation involved checking the supplies of raw materials and the equipment needed, as well as finding and training the staff to ensure the smooth running and the necessary quality checks. The numbers are telling.  It takes 280 components to make the Pfizer-BioNTech mRNA vaccine, involving 86 suppliers located in 19 different countries; these materials need to reach three different manufacturing plants, where the vaccines will go through a manufacturing process that involves 50,000 production steps; and at least 70 quality checks.   Now multiply that by the number of vaccines that have been approved.

Collaborations to make vaccines is not easy.  We have seen that even seasoned partners experience difficulties.  Emergent BioSolutions who were helping with the production of J&J vaccines threw away millions of doses, because they did not meet the necessary quality control.

We have been warning since March this year that some crucial raw materials are in short supply.  The late delivery of the bioreactor giant plastic bags can set back production by weeks, delaying the delivery of millions of much needed vaccines. In other cases, there are difficulties in finding the skilled technicians needed to oversee the production and check the quality and safety through the process. In addition, trade barriers are hindering the flow of these goods, the vaccines themselves.  We all recall the heartfelt tweet by Adar Poonawalla of the Serum Institute: calling on @POTUS to lift the embargo of raw material exports out of the U.S. so that vaccine production can ramp up.

We have been deeply concerned that despite our efforts, COVID-19 vaccines currently are not equally reaching all priority populations worldwide.  We have laid out five steps that urgently need to be addressed.  We are calling for dose sharing. We commit to support by making any uncommitted doses available.  We backed up our words with action within days, with 3,5 billion extra doses pledged by major vaccine manufacturers at the G20 Health Summit in May.

We are committing to continue efforts to optimize production.  The supply situation remains challenging for critical input supplies, such as bioreactor bags, single-use assemblies, cell culture media, filters, lipids, and vials & stoppers.  Vaccine innovators will of course continue to work closely with their suppliers to avoid disruption where they can.  But in the case that suppliers might have stocks that have not yet been tapped for whatever reason, we trust that the COVAX Supply Chain and Manufacturing Task Force can direct its immediate attention on creating a voluntary partnership to improve visibility of the supply of manufacturing input and to facilitate the establishment of global trade processes for the free movement of raw materials, vaccine components, and assay reagents.

We have learnt so much over the past 18 months and we will definitely be learning more as we hope to hit the target production to meet the world’s needs.  For innovative bio-pharmaceutical companies the work is far from over.  We have our work cut out for us.  We continue to prioritize the development of new COVID-19 vaccines, including vaccines effective against new variants, looking for new formulations for easier and longer storage.   For this work to continue, we urge governments to guarantee unhindered access to pathogens of any COVID-19 variants to support the development of new vaccine and treatments.  If this does not run smoothly, it will impact booster development and it will hamper the WHO’s ability to respond to the next seasonal influenza viruses.   In the last couple of days, we have joined the G7 future pandemic preparedness partnership to achieve a moon-shot target of 100 days to develop a vaccine in the case of a future pandemic.  Cutting down from the already historic 326 days to bring a first COVID-19 vaccine.

Antibiotic research leads start-ups to ruin (Taggesspigel)

Original article published on Taggesspigel on 15 June 2021. 

Mr Cueni, of all things, the COVID-19 pandemic, triggered by a virus, could further fuel the development of resistance in bacteria: many Covid 19 patients in hospitals are given antibiotics unnecessarily. G-7 health ministers are warning of a “creeping pandemic” and have been pushing for the development of new drugs for years. At the same time, pharmaceutical companies are saying goodbye to antibiotic research in frustration. How does this fit together?

Mr Cueni: In their analysis, politicians, scientists and industry agree: there is an urgent need for action. If COVID is a tsunami, then antibiotic resistance is a slowly melting glacier. According to the World Health Organisation, antibiotic resistance already kills 700,000 people worldwide every year. If we do nothing, by 2050 there will be ten million – per year. These are avoidable deaths. The keywords for solving the problem are well known: One Health approach, appropriate use, also in agriculture, surveillance, fair access for developing countries. And above all, innovative antibiotics; many of the current ones are no longer effective. Everyone is aware that the problem must be tackled at its root, and that root is: no new antibiotics are coming onto the market because there is simply no market for new antibiotics at the moment and antibiotic research is making start-up companies insolvent.

You are the Director General of the IFPMA, you represent the interests of these companies. Do you feel abandoned by politics?

Mr Cueni: Mutual recriminations are pointless. The German Chancellor was one of the first politicians worldwide to take antibiotic resistance seriously. That deserves recognition. But there is a difference between signing a summit declaration at G7 or G20 and signing a billion-dollar cheque to make antibiotics research profitable again.

The German pharmaceutical market alone achieved a turnover of almost 50 billion euros last year. Let’s be honest: What’s the matter?

Mr Cueni: The market situation for antibiotics is disastrous. In 2019 and 2020 alone, four companies had to file for bankruptcy. They could not continue to exist, even though they had brought new, successful antibiotics to the market and had received their approval, in some cases with priority, from the US Food and Drug Administration (FDA). Achaogen, for example, a start-up company from California, had not even achieved one million dollars in sales with its new antibiotic after 18 months.

How could it come to this?

Mr Cueni: For decades, antibiotics were neither used properly nor carefully in human and veterinary medicine. This has led to resistance. As a consequence, innovative antibiotics are being used today mainly as reserve therapies; they end up in cupboards of hospital pharmacies and are only used in emergencies when nothing else helps. However, these innovations are paid like antibiotics that were developed 30 or 40 years ago and have achieved large volumes over the decades, based on improper use. Thus, a new antibiotic makes very low sales but costs a lot of money in development and research, about 1.5 billion euros.

What makes research so expensive?

Mr Cueni: Developing new active principles is a scientific challenge; the low-hanging fruit has already been harvested. In addition, the regulatory requirements are high. For the clinical trials, you need quite a large number of patients, because the drug has to be tested widely. Company directors tell me that they have to invest in specially equipped factories for the production line in the early phase I of clinical trials. Afterwards, however, these factories stand empty and the manufacturers cannot sell their product because it is only needed as a reserve antibiotic. Companies that research antibiotics today and succeed are worse off than those that fail: because they lose money every day, while the others can at least write off their research costs. All of this is not productive.

What would be productive from your point of view?

Thomas Cueni: You have to decouple incentives from sales. We need to treat antibiotics like a fire extinguisher: everyone has it in the house, but no one hopes to ever need it. Nevertheless, everyone pays their fire insurance.

Are you calling for a premium for antibiotics?

Thomas Cueni: For example. Everyone who goes to hospital, for example because they want to have their knee screened, could pay a supplement of, say, five euros, which would then be used as a premium for antibiotics research. A Netflix model for reserve antibiotics would also be conceivable: One no longer pays per therapeutic dispensed, but rather an annual subscription, so to speak, for the reserve antibiotics, which are only used when needed, i.e. one decouples the price from the amount of antibiotics used. We have seen in research on drugs for rare diseases how strongly incentives can work by granting prices for these drugs that correspond to the rarity of the disease. One could also consider using patent protection as an incentive for research. Even an extension of patent protection from the current 20 to 70 years, however, would not bring much to new antibiotics as long as few are sold. It would be conceivable, however, that for every truly innovative antibiotic, the patent protection of another drug would be extended by six or twelve months. There are so many possibilities.

Admittedly, this means that not a single new antibiotic has been developed yet. And time is pressing.

Mr Cueni: Right. We need more venture capital, and above all we need it quickly. And that is why the industry is not whining but is facing up to its social responsibility and launched the AMR Action Fund a year ago. Twenty-three pharmaceutical companies have committed to providing a total of one billion US dollars as financing bridge for projects of start-up companies that want to make the jump from phase I to phase II and III. The fund management is independent in its decision-making about who gets funded. If the model works, it may be that one or the other start-up will one day find a place with the big players. In this way, we hope to bring two to four new antibiotics to market in the next seven to ten years. That is our contribution. However, this will only be successful and lead to more investment in antibiotics research if politicians have taken the right steps by then, so that antibiotics research can be financed sustainably in the future.

Vaccines against covid-19 could also be developed at a rapid pace because researchers cooperated internationally and building blocks for the innovative mRNA technology had been prepared years before. A model for antibiotics research?

Mr Cueni: The community in this area is clear, and of course it also exchanges information. But what has to be stated objectively is this: The difficult environment in commercial antibiotics research has led to many young people, even though they are fascinated by microbiology, not taking up their studies or changing careers. We are lacking the offspring.

Why?

Mr Cueni: When students see that there is little or nothing going on in their field at the larger research-based pharmaceutical companies, then they know that there will also be no demand for microbiologists. So we also need incentives for studies, we need an environment where, in addition to start-ups, large pharmaceutical companies are still doing research or are doing it again.

MSD, Pfizer and GSK are setting a good example here, because they never dropped out of antibiotics research. It is also gratifying that the company Roche re-entered the early phase of antibiotics research a few years ago and is now also participating in the AMR Fund.

Gradually, politicians and pharmaceutical companies are realising that the most modern cancer research is of little use if the patient develops a secondary infection in the meantime and the antibiotic is no longer effective. That is why, despite the dry analysis of the current situation, I am actually optimistic that something is now moving. Thanks to the leadership of countries like the Federal Republic of Germany and the United Kingdom, there seems to be a growing awareness at the G7 that the COVID 19 pandemic has caught the world on the wrong foot, so it is important to create the right incentives now when it comes to antibiotic resistance. The PASTEUR Act, which is being reintroduced in the US Congress this week, could be a ground-breaking global model in this regard because it contains both monetary incentives for successful investment in research and careful use of new antibiotics.