What You Need to Know About Developing Vaccines

An unlikely beacon of hope from the otherwise disastrous Covid pandemic, may come in the form of renewed attention towards approaches to vaccine development.

The Importance of Vaccines

The development of vaccines has been shown to be both lucrative and crucially important for disease control, both in humans and animals. The enormous variability in disease-causing agents and their variants requires a large repertoire of approaches to effectively present neutralizing epitopes to the immune system.

Traditional vaccination strategies, utilizing inactivated viral, bacterial, and toxoid preparations or live-attenuated strains, have successfully controlled diseases such as tetanus and polio. Safer formulations composed of purified polysaccharides, recombinant proteins or RNA have yielded effective vaccines against pathogens such as Streptococcus pneumoniae, Hepatitis B virus and coronavirus. In addition to infectious diseases, vaccines or vaccination approaches may also be used to treat for example oncological diseases.

Novel adjuvants; nanotechnology; new delivery systems; alternative delivery routes and vaccine strategies utilizing a multi-antigen expression platform facilitate new vaccination approaches.

General Development:

The development of a novel vaccine is a complex and lengthy process that generally takes 10 to 15 years.

• Laboratory research is typically conducted over 2 to 5 years to identify antigens containing the right neutralizing epitopes to include in a vaccine, and to evaluate antigen candidates’ ability to elicit the desired immune response, using the selected delivery route and method.
• Approvable, and correct quality (biological) starting materials must be selected early during this complex process and a robust initial manufacturing process must be developed that ensures the early tested leads are representative of the materials produced in a later phase.
• Only when the correct starting materials have been selected, and the manufacturing process has been selected, can toxicology evaluation, formulation, and development of a scalable, efficient, and reproducible manufacturing process take place; this can take around 2 years.

Clinical Studies

Usually after seeking scientific advice about acceptable potency and clinical parameters and after approval of an IND and/or an IMPD, the potential vaccine may proceed through three phases of testing in humans.

1. Phase 1 (2 years): the candidate vaccine is usually administered to less than 100 volunteers in a non-blinded study to determine safety, in order to proceed to phase 2, and to determine to what level of immune response can be induced.
2. Phase 2 (2 to 3 years): a larger group of participants receive the vaccine candidate and safety, immunogenicity, dosing, vaccination schedules, and delivery methods are studied.
3. Phase 3 (5 to 10 years): randomized, placebo-controlled, blinded pivotal studies generally involve thousands of participants to study vaccine safety and efficacy. These studies normally also include the evaluation of potential side effects in subjects, determination of the level of protection, and measurement of specific antibody induction or another approved clinical parameter when applicable.

Successful completion of clinical studies will demonstrate that the candidate vaccine is safe and effective and a Biologics License Application (BLA) or a Marketing Authorization Application (MAA) is submitted to applicable authorities to obtain a license. This entire process could take up to 2 years.

Vaccination Approach Selection

Vaccines are developed to present disease related epitopes to responsive immune cells that will initiate a protective/curative immune response. To achieve this many choices are to be made based on the understanding of the disease and its relevant epitopes, and subsequently based on the risks anticipated during manufacturing and during use in humans (or animals). As the quality of a biological substance may--to a large extent--rely on the validated capacity of the production process to yield a product of consistent quality, the careful choice of the vaccine approach becomes even more important.

Traditional vaccine preparations, utilizing inactivated viral, bacterial, and toxoid preparations or live-attenuated strains may involve less complex and low-cost manufacturing processes, are usually less safe, but may offer a strong and broad immune response. Safer formulations composed of purified polysaccharides, recombinant proteins or RNA may involve more complex and higher cost manufacturing processes. As these preparations in general offer a relatively limited set of epitopes, the obtained immune response may be less strong and less broad.

Quality Attributes

1. Potency: The antigen is most often a complex and heterogeneous structure, that may need an extensive package of analytical methods applied for its characterization. The analytical characterization of batches is needed to show essentially comparable quality between batches during development and after process changes. The limits of specification should be based on clinical experience and process validation in commercial scale. This characterization could also apply to the chosen adjuvant, e.g., when it is a biological component.

Freedom from adventitious agents: virus, TSE, and microorganisms, which could be present as a consequence of the biological production methods and biological starting materials. Next to quality control on raw materials, virus testing (and virus removal capacity), bioburden/sterility testing and aseptic control validation, an overall risk assessment for adventitious agents is required.

Can We Be Optimistic for the Future of Vaccines?

The short answer is yes.

With the establishment of new vaccine approaches including adjuvants; nanotechnology; new delivery systems; alternative delivery routes and multi-antigen platforms, it is expected that existing and new future diseases can be approached more effectively. Nevertheless, the development of vaccines still requires careful planning of the following aspects:

• initial lead optimization
• establishment of an initial manufacturing process
• subsequent upscaling
• adequate quality control strategy to ensure consistent vaccine production throughout development and commercialization.

ProPharma Group Vaccine Support Services:

ProPharma Group can assist you with many different types of vaccine projects and our experienced regulatory sciences consultants can offer support and guidance at each phase of development and throughout your product’s lifecycle.

We can support and author:

• scientific advice documents
• clinical trial applications
• authoring CTD sections
• PIP applications

We can support, consult, and advise on:

• reimbursement strategies
• post approval maintenance
• pharmacovigilance
• QP services
• importation services

Interested in learning more? Contact us today to find out how we can help with your global regulatory needs.