A regulatory view on Covid-19 vaccine outlook


One expert's take on the key issues at stake

Support efforts for the development, registration, and production of vaccines to stem the tide of Covid-19 are, of course, occurring busily on all shores.

Pharmaceutical Commerce caught up recently, via email, with UK native and longtime pharma R&D and regulatory expert Dr. Ash Ramzan, who shared insights on these pursuits from his vantage point as principal consultant with the firm Woodley BioReg Ltd, based in Huddersfield in West Yorkshire, England.

Ash Ramzan

Ramzan's lens is global, advising corporations in Europe, the US, South Asia, and Australia, as well as consulting with regulators such as UK’s MHRA, where, of late, he's been occupied with the agency’s recently issued Brexit post-transition guidance. Prior to joining Woodley, Ramzan worked for Ipsen Ltd (the UK division of the French Beaufour-Ipsen Group) as a technical affairs manager. He has also held a number of positions at Medeva Pharma in the UK during the scale-up and manufacture of Hepagene, a third-generation vaccine for hepatitis B currently approved in Europe.

The following are excerpts from our exchange on the Covid-19 product development, regulatory, and public-health pictures.

How would you assess the global response in working with manufacturers to speed up timelines for Covid-19 vaccine development (by doing things like compressing/overlapping clinical trials, using similar protocols and endpoints, etc.)?

From a regulatory perspective, there had already been developments in “smarter” clinical trials (adaptive clinical trials), which enabled a study to change direction partway through the assessment based on interim results. While such studies are limited in number due to the potential difficulties in agreeing the plans with regulators, their numbers have been bolstered recently through the need to address the coronavirus.

Another known method to accelerate the development of drug treatments is the use of challenge studies. These clinical studies deliberately seek to infect subjects following vaccination. Theoretically, such studies should present little risk to the subject, but given the many unknown factors in coronavirus vaccine development and performance, no such trials have yet been approved. Doing so would significantly accelerate the developmental vaccines into clinical use.

As late-stage testing gets underway for several candidates, given the pathology of SARS-CoV-2, do you think there are some technology approaches that may have better chances of delivering effective results?

The “art” of vaccine development is a complex and unpredictable one. A vaccine can only be developed and directed to parts of the virus molecule, and not all parts of the virus are susceptible to disruption equally, with the most effective and successful disruptions being to its genetic code. Given this, there is a wide range of potential approaches to vaccine development, including interventions that block the uptake of the virus into cells such as by blocking its replication by disrupting the transcription/translation pathways, preventing its maturation by disrupting any post-translation modification, and cutting off its release and infectivity to other cells.

Once the candidate technology has been selected (viral vectors, mRNA, etc.) the next key challenge is the “delivery” of the intended “art”, or technology, to the virus particles. There are a number of ways in which these “payloads” may be delivered, including the use of virus vectors that are developed and optimized to target specific types and classes of virus. The adenovirus vector has been used during one of the lead clinical development programs by the group in Oxford, UK, and AstraZeneca.

Given the ongoing work and urgency in finding a suitable vaccine, it’s unlikely that there will be any blockbuster approaches in their clinical development. The more likely and practically feasible approach will be to seek to modify and repurpose existing candidates and technologies to provide an early response to the pandemic.

It’s also anticipated that the global interest in viruses and the need for vaccines will significantly enhance the funding available to continue to research this area of preventative healthcare. This could lead to second and third-generation vaccines with greater efficacy and lower frequency of adverse events and the need for boosters.

How are industry and government agencies preparing to address potential supply chain issues, with the pandemic necessitating the need for “at-risk” production and large-scale manufacturing?

Vaccines are protein molecules and as such are susceptible to damage and degradation if they’re not stored and transported with care. This is already understood, and industry and governments are addressing these concerns by ensuring approved vaccines can be manufactured consistently and simultaneously in multiple large-scale manufacturing plants globally to the same quality standards. This has been possible through prioritization and utilization of existing approved manufacturing capabilities for biological and vaccine products.

While it’s understood that batches of vaccines are being manufactured “at-risk”, it’s important to note that this is not “at-risk” to the users, but “at-risk” to the product being approved. All pharmaceuticals, including vaccines, undergo a rigorous series of tests and evaluations through highly controlled clinical studies. Only following the completion of the clinical studies and independent assessment and verification of the clinical results will a potential vaccine be approved for use.

With a global population of over seven billion, all of whom will need to be vaccinated, the task of prioritization and administering coronavirus vaccinations will be a significant challenge. Different countries have taken various approaches based on their existing infrastructures. The US is setting up coronavirus-specific vaccination centers throughout the country; in the UK, GPs and other qualified healthcare professionals within the NHS will be utilized to administer vaccines. Other developed countries are following similar routes, with the WHO taking a lead in the distribution and administration of vaccines to less well-developed nations and healthcare systems.

Are there any distinctions or differences that could be impactful when you compare standards/guidance for approving Covid-19 vaccines among the FDA, NMPA, EMA, and MHRA?

Most of the global regulators work to an equivalent set of standards that are defined and documented with the ICH (International Conference on Harmonization) regulations; this includes the EU, US, Japan, and Australia. Many of the other regulatory bodies are also aligned with ICH regulations, including ASEAN and CIS regions.

While there are subtle differences in the type of information and data individual markets may require, all are aligned to the same key requirements for quality, safety, and efficacy.

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