Introductionary remarks by TextileFuture: “Why do we publish this article on the Swissmedic review of a COVID-19 vaccine? That is very simple, because we want for you to have a complete rundown of the procedures to authorise a COVID-19 vaccine. Other agencies might have different rules and regulations, but we wish to present the entire process in Switzerland, just to give you an idea, how much it takes before a vaccine is ready and authorised.”
First application for authorisation of a COVID-19 vaccine in Switzerland submitted Swissmedic has begun the scientific assessment of the first COVID-19 vaccine. The application for authorisation was submitted at the beginning of October 2020 by AstraZeneca, the company that is developing the vaccine in partnership with Oxford University.
The scientific assessment of the vaccine, currently bearing the designation COVID-19 Vaccine AstraZeneca, is undergoing what is termed a “rolling submission” procedure. This allows pharmaceutical companies to submit applications for COVID-19 medicinal products even before development work is concluded and prior to availability of the complete supporting documentation.
This procedure speeds up the process of deciding whether to authorise medicinal products: it enables Swissmedic to carry out the scientific assessment of non-clinical data from laboratory tests while clinical trials are still in progress. Trial results must then be submitted to Swissmedic for scientific review as they become available over the next few weeks and months.
However, no decision on authorisation can be taken until all the data needed to assess the safety, quality and efficacy of the vaccine have been submitted. The documentation must demonstrate how safe and effective the vaccine is in protecting humans against the new SARS-CoV-2 coronavirus.
Although Swissmedic is reviewing the dossier independently, it is working closely with partner authorities abroad on the scientific evaluation. Despite the high level of urgency, Swissmedic is reviewing the scientific data in accordance with its usual standards. Drug safety and the safety of the people who receive the vaccine are paramount.
Rolling submission
Rolling submission is a special form of authorisation for new active substances that has been adopted in the current pandemic situation and is intended to facilitate faster authorisation of urgently needed medicinal products. Using the procedure, Swissmedic can review data from ongoing clinical trials as soon as it is available.
Applicants do not have present a complete dossier when they first submit their application. Instead, they submit an initial data package containing such data as is already available and give Swissmedic a timetable for subsequent data packages.
Swissmedic assesses the data packages as it receives them, and questions are sent to applicants with a short response deadline. Rolling submission enables Swissmedic to build up a picture of the vaccine’s risk-benefit profile even before the pivotal clinical trials have been completed.
Vaccine authorisations: prevention rather than cure
No medicinal product can be placed on the Swiss market until it has been the subject of an application for authorisation. Vaccines for the new SARS-CoV-2 coronavirus or medicines to treat COVID-19 are essentially subject to the same requirements as all other medicinal products.
The procedure for assessing applications for authorisation centres on the risk-benefit profile of the medicinal product in question. Since vaccines are generally administered to healthy people on a precautionary basis, the requirements they have to fulfil in terms of efficacy, safety and quality are extremely high – in accordance with international standards.
Authorisation Prevention rather than cure
Claus Bolte is Head of Swissmedic’s Authorisation Division. Below he explains the difference between authorising vaccines and authorising medicinal products, describes the complex manufacturing process for vaccines and explains the situation as regards security of supply in Switzerland.
Vaccines are different
“Unlike medicinal products, vaccines are used in healthy children and adults. In other words, they are intended to prevent rather than treat disease. The requirements that vaccines have to fulfil in terms of efficacy, safety and quality are extremely stringent and comply with international standards. Just imagine: until recently one single authorisation involved two truckloads of data, all of which had to be reviewed in detail. Nowadays the data is read in and processed digitally. The data is automatically assigned and distributed to the members of our interdisciplinary case team. Before approving a vaccine, the team assesses the results of all clinical trials and reviews the product for potential immunological problems and manufacturing quality. The case team consists of toxicologists, pharmacists, chemists, pharmacologists and medics. During the review process they send questions to manufacturers or set out their objections in writing. Manufacturers have to answer the questions or resolve the objections within the specified deadline, otherwise their product will not be approved. Only then is the review process ended and the vaccine is approved.”
Manufacturing vaccines is a particularly complex process
“Vaccines consist of antibodies derived from living cells. All vaccines are based on a complex process, regardless of whether they’re for polio, tuberculosis, rubella or mumps. Until not so long ago most vaccines were for individual diseases. Combining several vaccines into what is known as a polyvalent vaccine is a fairly recent development, and one that is most pronounced in basic childhood vaccinations. In manufacturing terms, the process is even more complex than building a small car and is comparable in terms of workload. An additional problem is that vaccines are manufactured and filled in different countries. Since there are no longer any vaccine manufacturers in Switzerland, we are reliant on foreign producers. The Swiss SMEs that used to produce vaccines have now been bought up or have ceased research and production. We can’t force companies to manufacture vaccines in Switzerland. These days, the big conglomerates split the market between them. An additional problem is that from a manufacturer’s perspective, the Swiss market is small and complicated. There is no central purchasing, and the packaging materials and inserts have to be produced in the three official languages. What’s more, there are supply bottlenecks not only for vaccines, but increasingly also for medicinal products. The problem is particularly pronounced for antibiotics.”
Ensuring supply is a tricky business
“Each year, we receive between 12000 and 15000 applications for authorisation, which are reviewed by a total of 150 employees. These may be new authorisations, extensions of indications or variations to compositions and production methods. Vaccines account for less than two percent of the total. Our dependency on the international market causes the supply bottlenecks I’ve just mentioned, and which are often met with incomprehension by the public.
We at Swissmedic are frequently accused of not authorising enough vaccines. The sad fact is, though, that many vaccines never get submitted to us for authorisation in the first place.”
Covid 19 Research, testing and manufacturing
The coronavirus is currently holding the whole world to ransom. Ingo Matthes is head of the Authorisation sector’s Quality Review division. He and his team answer enquiries and are responsible for reviewing the quality-related aspects of applications for variations and new authorisations of vaccines and medicinal products. Since the coronavirus outbreak, he has also been a member of Swissmedic’s COVID-19 medicinal products task force. Here he explains the technical requirements associated with vaccine production.
All around the world, researchers are working flat out to find a potential vaccine for the coronavirus, among them researchers at the University of Bern and elsewhere in Switzerland. Ingo Matthes liaises closely with the researchers. “We hold what we call scientific advice meetings. A team of expert toxicologists and clinicians from Swissmedic comment on companies’ proposals, then suggest improvements that could further accelerate processes while still enabling companies to comply with safety requirements.”
Developing and authorising a vaccine
Although he is aware that “it can take up to 10 years to develop a vaccine of this type”, Matthes reassures us that “as we work with the industry, we will do everything in our power to minimise development time”. For example, there is the option of using scientific advice meetings to optimise clinical trial requirements at a very early stage and to shorten the development phase as far as possible. Clinical trials comprise three phases:
Once these three phases have been successfully completed – or possibly even earlier – an application for authorisation can be submitted. There are two types of authorisation procedure that can speed up the authorisation phase; the fast-track authorisation procedure (FTP) or the temporary authorisation procedure, for which certain clinical data can be submitted post-authorisation.
After this, the Federal Office of Public Health (FOPH) decides whether the vaccine is eligible for reimbursement by health insurance providers. Finally, the vaccine also has to be available, and it is the industry’s responsibility to ensure that this is the case. All this demonstrates that developing a vaccine is a complex process and that authorisation is anything but straightforward.
“We have to ensure that a vaccine that is administered to healthy children and adults does not cause any severe side effects”, says Matthes, summing up.
Close cooperation
As Ingo Matthes explains, international cooperation is one of the most important factors. “Close dialogue between researchers, authorities, manufacturers and countries is essential. This collaboration – driven mainly by Swissmedic – is working very well.” And how great are the chances of a coronavirus vaccine being discovered in Switzerland? “All I can really say is that Switzerland’s strong pharmaceutical industry and highly developed research and university structures mean it has excellent resources for researching, developing and producing vaccines. Nevertheless, the fact is that institutions and researchers around the world are working towards the same goal. At the end of the day, though, it doesn’t matter who finds the vaccine, just that one is found as quickly as possible.”
Authorisation of medicinal products for the prevention and treatment of COVID-19
Swissmedic offers various regulatory procedures for authorisation and variation applications relating to medicinal products, including vaccines, used to prevent and combat COVID-19. Companies submitting corresponding applications during the current pandemic are given maximum flexibility so that Swissmedic is able to fast-track its decisions and patients have access to safe, effective and high-quality medicines as quickly as possible.
The Guidance document Authorisation procedures for Covid-19 medicinal products during a pandemic describes the various scientific advice options and the regulatory procedures for authorisation and variation applications for COVID-19 medicines.
For pandemic medicines, Swissmedic provides an option for the gradual submission of the authorisation application (“Rolling Submission”). This allows pharmaceutical companies to submit applications for COVID-19 medicinal products even before development is concluded and complete documentation is available.
Furthermore, Swissmedic has adapted the requirements applicable to product information and packaging texts for medicinal products used to prevent and combat the new coronavirus SARS-CoV-2. The guidance document also includes important questions and answers (link to FAQs).
The guidance document enters into force on the date of publication and will apply immediately to all incoming applications connected with the COVID-19 pandemic.
Pre-Submission and Scientific Advice Meetings
Swissmedic offers the option of advice meetings to research groups and the pharmaceutical industry with the aim of supporting development programmes in an efficient and targeted manner, discussing scientific data and fast-tracking authorisation applications for COVID-19 medicinal products. These measures are designed to ensure that patients have the earliest possible access to safe, effective and high-quality medicines used to prevent and combat the new coronavirus.
Swissmedic also works in close scientific collaboration with expert groups and with national and international authorities so that it can fast-track authorisation procedures and react quickly to new developments.
The Guidance Document can be downloaded here