What did we learn from the 2009 pandemic?

In April 2009 we were in the middle of an ongoing influenza pandemic and as the Executive Director of the European Medicine Agency I was ultimately responsible for the Agency’s response.

EMA’s responsibility was to ensure that we could get a vaccine approved as soon as possible and evaluate potential antivirals for the prevention and treatment of the infection. We also set up a robust surveillance system monitoring the safety of vaccines and antivirals when they were put on the market. All of this had to be done while ensuring that staff and experts working at the agency could continue to operate and deliver advice to developers of vaccines and antivirals while maintaining their own wellbeing.

It was an intense period with many meetings, ensuring the operation of the agency as well as daily teleconferences with European Commission, WHO, other regulators such as the FDA, and the industry. Luckily there were preparations in place.

When the pandemic broke out in April 2009 we were not taken by surprise. Warning signals came from WHO as early as the beginning of 2000. The SARS outbreak in 2002 had also served as a wakeup call. The outbreak of bird flu caused by H5N1 virus was an additional indication that a pandemic was imminent.

Pandemic preparedness work at EMA had therefore already started in 2003 in collaboration with the European Commission, Member States of the European Union and the European Centre for Disease Prevention and Control (ECDC). In 2006, we put in place a crisis management plan to outline the management structures and detailed procedures to support the processes associated with an influenza pandemic. The plan set up detailed procedures for fast-track approval of pandemic influenza vaccines via the centralised procedure and post-authorisation follow-up (including assessment of safety signals) of centrally authorised pandemic influenza vaccines and antivirals.

During this period there was increased involvement of EMA staff, EU Commission and experts from member states and many innovative proposals on how to speed up the development and authorisation surfaced.

One of these was the idea[LS1]  to create what became known as the Mock-up vaccines. Specific guidance was developed by the Agency for an assessment procedure for pandemic influenza vaccines. This innovative ‘core pandemic dossier’ approach, based on decades of experience with seasonal flu vaccines, was designed to speed up the scientific evaluation of pandemic influenza vaccines to be able to authorise a vaccine before a pandemic reaches its peak. In practice, safety and immunogenicity data was generated based on the respective mock-up vaccine. These were then extrapolated to the same vaccine containing the pandemic strain. Supplemental clinical trial data with the new strain was then created during a rolling review and continued once the product was on the market.

There was naturally high interest from the leading vaccine manufacturers to support this concept by participating in the development. Between 2004 and up to the start of the pandemic in April 2009 four mock-up vaccines had received authorisation in the EU via the centralised procedure.

After the WHO identified the pandemic strain, H1N1, it was incorporated in the mock-up vaccine. A simple regulatory variation procedure was then used to confirm the marketing authorisation for the new pandemic vaccines.

Thanks to this preparation and the innovative mock-up concept we were able to get a vaccine to the market in record time. The pandemic was declared in April 2009 with the A/H1N1 new strain and the approval of the variation for Pandemerix and Focetra was granted on 29 September 2009 followed by Celvapan 6 October 2009.

Shortly after this, mass vaccinations started and luckily the manufactures were well prepared and quickly ramped up production. At this stage EMA’s focus shifted towards the extensive pharmacovigilance system that we had in place to follow up the safety of the vaccines.

The work that we and many others put into this and the speed at which a vaccine was put on the market had a major impact of this pandemic in my opinion, and the WHO could declare that the pandemic was over on the August 10, 2010. This was a live pandemic experience and the lessons learned are extremely valuable in tackling the new SARS-COV-2 pandemic virus.

There are however some fundamental differences between the 2009 pandemic and today’s pandemic.

For starters, the new virus is not an influenza virus, but a coronavirus. We don’t have an approved vaccine or a prepared mock-up vaccine against this type of virus like we had for influenza. Some (unsuccessful) research on a coronavirus vaccine was done during SARS and MERS epidemics but when these outbreaks disappeared companies halted this research. We therefore lack the level of experience and preparation that we had for the H1N1 pandemic.

Vaccine development therefore must go through much lengthier development programs with phase 3(or phase 2[LS2] [TL3]  studies with conditional approvals?) studies before these products can be approved for mass vaccinations.

It will be a delicate decision to find the right balance on the benefit / risk regarding efficacy and safety with high levels of uncertainty. Regulators will find themselves making decisions where an urgent need for a vaccine to save lives has to be balanced against uncertainty about the safety and efficacy of the products in different risk groups.

On the antiviral side there is also a different situation compared to the pandemic in 2009. Then we had approved drugs on the market for influenza. For Covid-19 no antiviral has been approved and experience in developing drugs against this virus type is very limited. There are however many different development projects ongoing currently to bring antivirals against this virus to the market. Repurposing old drugs is one approach and there are many clinical trials in place. A new vaccine will take time to develop before vaccinations can begin so finding an antiviral that[LS4]  could minimise the severity of the virus and reduce the mortality rate is therefore urgently needed.

Compared to the 2009 pandemic the need for a diagnostic test is more urgent today since testing, both to confirm cases and to confirm immunity, is essential to manage the epidemic. In 2009 we already had test systems up and running based on yearly influenza surveillance. There is now rapid development of new tests for Covid-19 and many are entering directly into the health care systems and even offered directly to the general public. This[LS5]  development raises concerns that in some countries lack of validation and proper approval putting life at risks.

There are a lot of differences between the 2009 pandemic and today’s Covid-19 pandemic. We had availability to vaccines, antivirals and diagnostics in a short period of time into the 2009 pandemic. It is obvious that we don’t have the same situation today. However, the 2009 pandemic gave valuable experience to regulators’ around the world on how to handle a pandemic from all aspects of management, organisation and collaboration. Regulatory agencies such as EMA and the FDA therefore stand strong with legislative, procedural tools and experience to facilitate the availability and approvals of vaccines, and therapeutics.

By Thomas Lönngren
Strategic Advisor
NDA Group
www.ndareg.com

References

  1. https://www.ema.europa.eu/en/documents/report/pandemic-report-lessons-learned-outcome-european-medicines-agencys-activities-during-2009-h1n1-flu_en.pdf
  2. https://www.ema.europa.eu/en/documents/other/ema-plan-emerging-health-threats_en.pdf
  3. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders