Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Options of innovative vaccine approval without human efficacy data ***

Dr. Thi Hong Nhung Do (Abschlußjahr: 2017)

Summary
Language: English
The development of vaccines is crucial for the protection against severe infectious diseases. Applicants aiming at approval of a new marketing authorization need to confirm efficacy, safety and harmlessness of the innovative medicinal product. Different from standard drug products, vaccines need to demonstrate protection against a disease (protective efficacy). Sometimes, low, unpredictable or no occurrence of disease outbreak makes human efficacy trials not possible or feasible. The regulatory agencies have recognized these limitations and propose alternative approaches for the determination of vaccine efficacy.
Animal efficacy studies can be used to extrapolate to human efficacy. Importantly, an adequate animal model with similar immune response to human is required. With introduction of the Animal Rule in 2002, the FDA has established an extra approval pathway, which explicitly accepts animal efficacy data. The first vaccine (against anthrax) received approval following the Animal Rule already. The EU legislation accepts animal efficacy data, depending on the individual vaccine and targeted disease. A vaccine against the eradicated disease smallpox received marketing authorization under exceptional circumstances with the use of animal efficacy studies.
Deliberate exposure of infectious agents to human volunteers is another option for the evidence of efficacy. These studies have to be ethically justified and performed in a controlled setting. Modification of the challenge agent may influence the comparability to the wild type pathogen. Established human challenge models are currently used for the proof of concept in vaccine development to support marketing authorization applications. Similar to human challenge trials, passive protection studies are mainly used for the proof of concept or as supportive data in the dossier of a marketing authorization application. Hereby, antibodies against a disease are applied to naïve animals, which thereafter are challenged with the pathogen. This method allows a quantification of the protection level and is mainly used in research programs.
Development of an immune response after vaccination is the essential mechanism of action for vaccines. The production of antibodies can be used to correlate and extrapolate data from literature information or comparable vaccines. This instance is used for marketing authorizations based on the comparison of the immune response. In addition, demonstrating non-inferiority in immune response enables bridging of data to new populations, age group or manufacturing conditions for a change of the vaccine’s specification or indication.
From the presented methods, especially nonclinical efficacy trials and the comparison of immune response are the most well-known and accepted strategies. The severity of disease, availability of alternative medical care and other supportive data as well as the individual safety profile of the innovative vaccine influences the decision on marketing authorization and should be discussed individually in scientific advice procedures with the regulatory authority.
Pages: 37