EMA’s Article 58 procedure and WHO’s prequalification procedure – pathways to licensure worth to consider for vaccines and other medicinal products

by Michael Pfleiderer

There are challenges and opportunities for developers of vaccines and other medicinal products needed outside the EU but having a high potential of becoming essential medicinal products also within the EU. The Article 58 procedure is reserved for products that are not (or not yet) foreseen for EU markets. The EU Article 58 procedure and the WHO prequalification procedure have been revised and now provide excellent opportunities to drug manufacturers. In this article, Michael Pfleiderer provides a detailed overview on the Article 58 procedure and WHO’s prequalification procedure.

Pregnant women and vaccines against emerging epidemic threats

by Michael Pfleiderer

Vaccines have one of the highest live saving potentials amongst all medicinal products licensed around the globe. One commonality of all these vaccines is that they are developed for all age and risk categories except pregnant women. Although some vaccines are specifically recommended for use in pregnancy, access to novel vaccines is generally blocked for pregnant women. Michael Pfleiderer summarizes which advances have been made to overcome this dilemma.

The value of human challenge trials in vaccine development

by Dr. Michael Pfleiderer

Clinical trials in vaccine development are often hugely dimensioned sometimes comprising several ten thousands of individuals for phase III safety and efficacy studies. These sample sizes are required in order to demonstrate efficacy of vaccines for which no correlate of protection exists or for which very rare severe adverse effects need to be investigated pre-licensure. Besides the ongoing debate whether regulatory practice should ask for even more extended studies or whether there should be an upper limit of study sizes in order to ensure that clinical studies continue to be feasible, controllable and affordable there is an increasing number of vaccines that cannot be investigated for efficacy for several reasons.

These belong to the growing group of vaccines against newly emerging or regularly re-emerging pathogens such as Chikungunyavirus, Ebolavirus, MERS and SARS Coronavirus, West Nil Flavivirus, Zikavirus as well as against numerous microbial pathogens and parasites. Diseases caused by many of these pathogens do not occur regularly but appear and disappear in unpredictable epidemiological patterns making it virtually impossible to design a field efficacy trial since the region of emergence or re-emergence is unknown.

Seasonal influenza vaccination and the vision of next generation vaccines

by Dr. Michael Pfleiderer

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Holiday season is over and seasons quickly turn from summertime to wintertime. Shorter days and colder temperatures are accompanied by the yearly official reminders released by vaccination advisory committees not to forget the annual shot of influenza vaccine in order to update immune protection against drifted influenza virus strains.

Meanwhile, numerous vaccines are available including tri- and tetravalent vaccines, inactivated and live attenuated vaccines, unadjuvanted and adjuvanted vaccines. Moreover, age indications are very heterogeneous ranging from 6 months of age upwards to over 65 years only.

This puzzling situation is further complicated by the fact that efficacy and effectiveness of various seasonal influenza vaccines is quite heterogeneous in different age and risk categories turning choice of the right vaccine into a difficult exercise for both, doctors and vaccines. Furthermore, the short shelf life naturally inherent to seasonal influenza vaccines is problematic for regions with untypical and repeated epidemiological patterns not matching with those of the Northern or Southern hemispheres for which most of the globally available influenza vaccines are tailor made for.

For those regions, suitable vaccines are either not available or shelf life of available vaccines may have already expired when these vaccines are needed. To simplify these rather complex scenarios scientists and regulators call since a long time for next generation influenza vaccines providing broader protectivity across strains and seasons, circumnavigating the need for seasonal revaccination and being freed from stringent production cycles. WHO is coordinating these initiatives and has recently launched a Preferred Product Characteristics (PPC) document summarizing the requirements for better or next generation influenza vaccines. We have been deeply involved in these activities by contributing to the drafting and finalization process of the PPC document. Read more about the WHO PPC concept.

How to license vaccines against new and emerging infectious diseases fast and effective?

Recent past has repeatedly taught us that influenza pandemics probably no longer constitute an immediate health threat for the global population. Other infectious diseases have caught up outnumbering pandemic influenza in number and sequence of events. WHO and other public health institutions regularly report on outbreaks mainly caused by viral infectious agents such as MERS, SARS, West Nile Flavivirus (WNV), Ebola, Chikungunya, Zika, Dengue viruses and so on. Barely any of these infectious diseases is preventable by vaccination and none of them is curable by antiviral treatment. Although regulatory authorities offer all their support to facilitate development and licensure of safe and effective vaccines against these diseases there are, with one exception, no appropriate vaccines licensed and available.

Pre-empting and responding to vaccine supply shortages

Industrialized country markets are generally perceived as being protected from supply shortages and out-of-stock situations. Essential medicinal products, however, seem to become a continuous exception from this rule. Experience from recent years documents that a growing list of important medicines cannot sustainably be provided in sufficient quantities imposing critical burden to patients and public health systems.

To a significant extent this list also includes vaccines which are temporarily unavailable causing turbulences in national vaccination programs resulting in adaptations of official vaccination recommendations, postponement of required vaccinations or no vaccination as the most extreme consequence.

Scientific and regulatory aspects facilitating global availability of better influenza vaccines

Amongst infectious diseases influenza regularly wins the pole position due to the particulars of seasonal epidemiology and the persistent risk of emerging pandemic influenza virus strains. While the logistics behind manufacturing and delivery of seasonal influenza vaccines are manageable in industrialized countries less wealthy regions of the world are often underprivileged regarding sufficient and timely procurement with appropriate vaccines.

Burning issues in vaccine development

Reflections regarding the current global challenges in the vaccine field

During the past couple of years number and extent of critical topics related to vaccines were steadily growing. First, frequency of outbreak events has increased accompanied by no or only late coming preventive options. Second, only few pharmaceutical companies are left having the knowledge and the financial resources to produce vaccines and to invest into development of new products. Third, despite all these efforts expanding global markets cause dramatic supply problems for many vaccines. Critical supply issues are no longer restricted to low or middle income countries but also widely concern the high income countries.