Boosting vaccine development and production in a post-pandemic era with fast, high-performance immunoassays: Part II
Vaccine bioprocess development and production
Only clean drinking water can match vaccination in its ability to save millions of lives every year. In the case of the ongoing COVID-19 pandemic, the availability of a vaccine is considered a prerequisite for a return to normal life worldwide. But transforming antigens into robust vaccine products is a lengthy process. In the second article of this two-part series we will look at some examples of how immunoassays can play a key role in delivering reliable vaccine bioassay data to support efficient bioprocess development and production to ensure that vaccine production lots meet targets, time and time again.
Discovery is one thing. Establishing a robust bioprocess workflow and manufacturing is something else
Vaccines are highly complex products. QC takes up 70% of the time of production of a vaccine and includes between 100 and 500 quality checks throughout the process. Vaccines can be on the market for many years, even decades, and the lead time to produce a vaccine lot ranges from several months (influenza vaccine) to three years (pentavalent and hexavalent combination vaccines), with vaccine shelf-lives generally ranging from one to three years.
Significant changes in the manufacturing process will typically trigger regulatory change submissions, in extreme cases requiring bridging clinical studies to show equivalent immune response and safety outcomes. This means that getting it right from the beginning is vital. Emphasis on streamlining process development is a major success factor in being first to market and inadequate process development is often implicated in late stage product development failures. It’s all about maintaining a balance between speed to market and process optimization; getting to market earlier increases revenue in the short term but locking in a further optimized process may generate cost savings over the entire vaccine life-cycle.
The need to increase efficiency in vaccine production has included a move toward using risk-assessment tools and the principles of quality by design (QbD) to build quality into bioprocesses instead of relying on final-product testing. This approach requires real process understanding, in-process testing using process analytical technologies (PATs), feedback control, and continuous improvement over the life cycle of each product. Process parameters and performance interactions should be understood outside the range required for acceptable product quality (1).
Choosing an immunoassay platform to meet your vaccine bioanalytical needs
Early optimization of bioprocess workflows based on reliable assay data will greatly increase the chances of success by ensuring long-term efficiency and reduce the need for changes that require lengthy re-validation. Here are some examples of how robust immunoassays can be used to generate data for Critical Quality Attributes (CQA) used in QbD to help in vaccine bioprocess development and manufacturing, and a few key factors to consider when choosing an immunoassay platform.
Antigen titer – broadening the analytical range
Efficiency in antigen titer bioanalysis during bioprocess development means spending less time on diluting samples to acquire in-range data and avoiding re-analysis. When it comes to immunoassays to determine CQAs such as antigen titer, for example, this means using a technology that provides high quality data over a broad analytical range.
Robust measurement of HCP impurities throughout a vaccine bioprocess workflow
Vaccine purity can be critical in avoiding adverse reactions, and one possible cause of adverse reactions is host cell protein (HCP) impurities in the vaccine. The levels and profiles of HCP impurities in biologicals such as vaccines must therefore be documented to meet regulatory requirements and to understand the consistency of the biological product and manufacturing process. This generally involves implementing immunoassays targeting generic or specific HCPs to support process development/changes and process and product understanding.
It is generally accepted that a sensitive, validated method is required to monitor residual HCPs in accordance with regulatory guidelines. Based on risk assessments, clinical experience and manufacturing capability typically accepted levels are <100 ppm (100 ng HCP/mg product). The gold standard has been ELISA, backed by high quality antibody reagents. But this rather tedious and time-consuming analytical method can have its drawbacks, for example in matrix interference that leads to poor dilutional linearity when analyzing the broad range of samples involved in a bioprocess workflow. A platform of choice will ensure minimal matrix interference to give robust analysis.
Potency testing to support formulation
Assessing batch-to-batch consistency in potency is an important component of vaccine QC and must be determined at the time of release (2). This testing can be used in stability studies, validation and optimization of fermentation and purification, comparing new facilities, and evaluating the effect of changes in formulation or adjuvant.
The choice of bioanalytics largely depends on the mechanism of action and ability to ensure lot-to-lot consistency. Live vaccines often require animal- or cell-based assays to ensure infectivity, whereas recombinant vaccine potency can be reliably monitored with in vitro relative potency (IVRP) immunoassays to support formulation and for the GMP release and stability testing of clinical drug substances and drug products. If immunoassays are to be used for serological analysis based on animal models to generate an ED50 value, then a number of factors must be considered:
- Large numbers of samples
- Tedious work
- Low sample volume, especially of the pre-bleed samples
- Variability in animal studies
- Regulatory issues
The challenge is to find an immunoassay to determine vaccine potency that can quickly deliver reliable and robust data from large number of samples with small volumes.
A number of leading vaccine manufacturers have been faced with these challenges and have chosen Gyrolab® technology as a solution to help boost the efficiency of their vaccine R&D, bioprocess development and manufacturing.
- Ozturk SS, Jenkins N. New Directions in Pharmaceutical Process Development and Manufacturing: Process Analytical Technology (PAT), Quality by Design (QbD), Design Space (DS), and Other FDA Initiatives. Proceedings of the 21st Annual Meeting of ESACT1, 2012: 731–733.
- Knesevic I. Stability evaluation of vaccines: WHO approach. Biologicals: journal of the International Association of Biological Standardization 37, 357–359, discussion 421–353, (2009).