Regulatory Challenges For Viral Vectors For Cell And Gene Therapy

By Barbara Gilmore, Senior Consultant, Transformational Health, Frost & Sullivan

Frost & Sullivan recently invited industry leaders with viral vector experience in cell and gene therapy to participate in a new and unique thought leadership forum, our Virtual Think Tank (VTT) series. This forum brought together leading minds in this emerging field to discuss the current state of regulatory issues around viral vector manufacturing, key challenges, and other insights related to viral vectors.

Gene therapies transfer genetic material to a patient to modify a gene triggering a disease, with the goal of effectively treating that disease. Gene therapy development and production is a complicated endeavor that involves collaborative input from academic, industry and government entities. Numerous global regulatory agencies have published guidelines and regulations directing this type of work, but not all guidelines are aligned.

Advances in gene therapy and the introduction of genetic material using viral vectors come with a therapeutic benefit. However, there are challenges on the development side. Viral vectors differ significantly with regard to their virulence and replication status. Viral vectors can be 1) integrating (i.e., retroviral and lentiviral vectors), which incorporate a specific transgene into the host’s chromosomal DNA, or 2) non-integrating (i.e., adenoviral, herpes, and AAV vectors), which do not assimilate the desired transgene into the chromosomal DNA but instead leave the transgene inside the nucleus.

Viral vector production is complex. For one thing, legacy technologies adopted from the academic research side are hard to scale up. Also, technology challenges coupled with talent shortages are a further bottleneck to expanding capacity. The relatively young cell and gene therapy market is highly fragmented globally. Few contract research and manufacturing organizations (CMO/CROs) are commercially scaled to assist with viral vector demands and shortages. Only a handful of the larger companies are capable of commercial-scale production, and solutions that allow companies to expand their own capacity are limited.

Guidances from the National Institutes of Health (NIH) and Centers for Disease Control (CDC) are not well defined. The Food & Drug Administration (FDA) and the European Medicines Agency (EMA) guidelines for Good Manufacturing Practice (GMP) regulations related to regenerative medicine development workstreams are helpful, but they differ between agencies and are not fully compatible. These differences can confound companies making and marketing products globally.