Gene treatments based on viral vectors are here to stay. Keeping up with rising demand necessitates a thorough examination of issues, the opportunity for standardization, and planning for faster patient access.
Gene treatments based on viral vectors have become a reality in the last five years. The US Food and Drug Administration has authorized eight medicines using three different viral vectors: adeno-associated virus, lentivirus, and herpes simplex virus.
When adjusted by dosage quantity, the extraordinary demand and at-risk financing for COVID-19 vaccines allowed for a ten- to hundred-fold increase in manufacturing, with over two billion doses of the AstraZeneca viral-vector-based vaccine already created.
Challenges Of Viral-Vector Manufacturing
There are three key hurdles to large-scale viral vector production that influence the various stages of viral vector development. They revolve around the importance of selecting the right production system, optimizing downstream processing, and developing standardized chemistry, manufacturing, and control processes and quality tests.
There is no one manufacturing method that is appropriate for all assets.
Flexibility, scalability, and quality are still trade-offs among contemporary upstream production systems. All three requirements must be met to quickly create and market a safe and effective blockbuster product.
Developers must make an early decision based on their trust in the present construct, the size of the possible patient group, and the market environment since no one platform currently meets these requirements.
Downstream processes are hampered by individual optimization and low yields.
DSP is now challenged by a lack of standardization and poor yields, which leads to a significant reliance on human skill and the omission of quality-enhancing measures. Furthermore, no standardized platform method for commercial-scale viral-vector DSP exists.
Physical properties vary greatly amongst viral vectors, as does the degree to which they accumulate inside cells vs. in the medium. This makes creating platform techniques with known output outcomes difficult.
A solid working relationship with authorities to prevent delays.
Enhanced quality and CMC instructions are required due to the industry’s limited experience with commercial, at-scale delivery of viral-vector gene treatments. Regulatory agencies have published specific advice for cell and gene treatments, which is always expanding.
Agencies have erred on the side of caution due to a lack of long-term safety data and the risk of accidental changes to patients’ genetic makeup; agency requests for additional information regarding CMC control, GMP certification of materials, and potency assays are notable examples of such delays.
Another issue is the transition of production from preclinical to clinical and commercial standards, which has caused some clinical trials to be postponed.
Final Thoughts
As new items enter the market, regulatory guidelines will change and become more complex. As analytical technologies for comparability studies advance, this might lead to more detailed recommendations on potency assessments and clearer approaches for switching production systems.
FDA questions from a recent gene therapy hearing reveal that regulators weigh the feasibility and necessity for maximum virus dose regulation. The wide diversity of products and viral-genome load vs. capsid exposure complicates regulatory bodies’ efforts to establish acceptable dosage levels.
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