In a white paper from SGS in September 2022 the importance of “analytical biosafety testing” and “advances in developing scientific technologies” was emphasised as crucial in preparing for the “next pandemic”. The paper reflects that before the COVID-19 pandemic, the fastest vaccine ever developed was for mumps. This took 4 years. Since then, the COVID-19 vaccines we developed in just 326 days. This was a “previously inconceivable feat and an undisputed ‘scientific triumph’”. Despite the acknowledged success of this development, lives were lost while we waited. Thus, future “rapid vaccine development” will be “essential to minimise future transmission, serious illness, and fatalities”.
CEPI’s goal, supported by governments across the world, is that “vaccines should be ready for initial authorisation and manufacturing at scale within 100 days after the next pandemic pathogen is recognised”. Ambitious, yes, but central to a public health response. With this ambition comes a concern that “expedited timelines” could compromise both short- and longer-term safety of vaccine candidates. Combining this with vaccine hesitancy, there are “significant ethical, scientific, and regulatory hurdles” to overcome. The questions asked by SGS are:
- Analytical biosafety testing of vaccine candidates remains critical, but how has COVID-19 enhanced the function?
- And how can the mission-critical compliance obligation be harnessed to support the rapid, compliant, and successful development of tomorrow’s vaccines and biologics, today?
Analytical biosafety testing
The paper explores the “what” and “why” of this “essential component of vaccine development and manufacturing”. The process “safeguards the integrity” of products and “plays an important role in delivering safe supply to patients”. Furthermore, it is “pivotal to upholding regulatory compliance and supporting expedited time to market” as well as return on investment. So why do we need to avoid viral contaminants? Contaminated vaccines. SGS identifies a 2010 identification of Porcine Circovirus type 1 (PCV1) DNA in rotavirus vaccine products. Luckily, when tested in human cell lines, productive PCV1 infection wasn’t observed, but this “serves as a cautionary tale”.
“Testing of source materials and products is a fundamental step to screen for contaminants and assure vaccine purity.”
The paper highlights the importance of an “appropriate viral testing strategy” that considers starting materials and reagents as well as the “nature and intended use” of the product. Several approaches are used throughout the testing process, such as general assays, species-specific assays, and assays that detect virus markers. The approach must be “holistic”.
The paper reminds us that we have specific regulatory authorities to ensure this testing is carried out. Guidelines, such as WHO guidelines and FDA guidelines, are stringent, on top of country-specific requirements.
Credit to COVID-19
SGS suggests that COVID-19 “disrupted the compliance framework” when members of the International Coalition of Medicines Regulatory Authorities (ICMRA) vowed to “strengthen global collaborative efforts to align the facilitation of rapid development, approval, and global roll-out of safe and effective medicines to prevent and treat COVID-19″.
The pandemic brought the importance and workings of analytical biosafety testing into a “much sharper focus”. The biggest challenge was to accelerate operations without compromising quality. The key, SGS believes, was “embracing rapidity and clear communication”.
SGS Centre of Excellence
Over recent years, SGS’ Biosafety Centre of Excellence has increased its capacity for testing cell banks for vaccines, therapies, monoclonal antibodies, and other recombinant protein-based biological medicines.
“SGS is committed to rapidly delivering expert resources to safeguard patient safety, through fast and effective pre-clinical testing.”
In 2020 SGS joined forces with infectious disease, research and innovation, and pharma specialists to “rapidly develop, scale up, and produce a potential vaccine”. Led by the Jenner Institute at Oxford University, the consortium relied on a precise testing strategy as well as “cutting-edge facilities”. By April 2020 thousands of doses were delivered for clinical trials. In June 2020 SGS invested in “bolstering its capability, hiring and training 35+ full –time employees, and delivering testing”. This was intended to “accommodate increasing demand with speed and accuracy”. By the end of 2021, 3 billion doses of the vaccine had been administered across 180 countries.
Foundations for future breakthroughs
The paper identifies vaccines other than the COVID-19 vaccines as having a “substantial” positive effect on human health. For example, the HPV vaccine is “cutting cervical cancer” by almost 90% in people who take it. Professor Peter Sasieni, director of clinical trials at King’s College London, says that “such dramatic reductions in cancer” will lead to a change in the screening programme. This is good for patients but also offers a cost-effective operation for healthcare providers, emphasising “prevention vs cure”.
SGS’ top tips for best practice
- Scope requirements during the pre-clinical stage
- Engage a specialist outsource partner with access to expert people, robust processes, and effective technology
- Ensure compliance with current ICH/and or FDA and/or European Pharmacopoeia guidelines
- Take a risk-based approach to execute a scientifically justified testing strategy
- Capture data from appropriate tests at different stages of development and manufacture
- Address highly product-specific requirements
- Implement Good Manufacturing Practice (GMP)/Good Laboratory Practice (GLP) compliant testing
- Prioritise interaction and ongoing discussion, as appropriate, with key stakeholders
Recognising that all testing methods have an “important place in the creation of a holistic analytical biosafety testing strategy”, SGS suggests that Next Generation Sequencing is a “rapid, scalable, and high throughput method”.
“Using NGS, a population of sequences in the sample can be surveyed, allowing the detection of unknown viruses, integrated retrovirus, provirus, transcripts, and endogenous sequences.”
This way, less sample input is needed for “highly accurate” results. NGS also promotes faster and more cost-effective studies. It is a “powerful tool” that SGS considers will ‘revolutionise vaccine development”.
SGS’ summary
Although “no amount of testing” can give full confidence in the “absence of an infectious agent”, SGS recommends a risk-based approach. This should combine methods, dependent on “factors such as the production parameters, the viral risk assessment of raw materials, and the clinical application of the product”.
The intensity of the COVID-19 vaccine development has “irreparably transformed” approaches. This will be “finetuned” in the future, and analytical biosafety testing will “form a key part of this broader post-pandemic technology”.
We look forward to hearing more from SGS at the World Vaccine Congress in Europe 2022. To join us, and them, get your tickets here.
For the full paper click here to download a copy.
