Gene therapies provide life-changing outcomes for patients and some have the potential of being curative. The market for viral vector-based gene therapies has advanced in recent years with the first approvals occurring in 2017 and 2019 for Roche’s Luxturna® and Novartis’ Zolgensma®, respectively. In 2019, the US Food and Drug Administration (FDA) predicted a significant increase in the number of cell and gene therapy Investigational New Drug (IND) applications and approvals between 2020 and 20251. As innovator companies plan the clinical path for their gene therapy, strategies for manufacturing and clinical supply should be developed early to help avoid delays in later Phase studies or regulatory review.
2020 saw an atypical delay in gene therapy approvals by the FDA. The pandemic certainly played a role with some clinical trial timeline delays, combined with COVID-19 vaccine and therapies focus. These additional treatments competed for review time with gene and other therapies. Additionally, some gene therapies were delayed due to issues within the chemistry, manufacturing and controls (CMC) section of their submissions.
Gene therapy companies are forging new paths when it comes to scalable manufacturing. Unlike more mature biologics such as monoclonal antibodies, gene therapies do not have a standardized manufacturing platform or process. Additionally, the development timeline for gene therapies can be years shorter than monoclonal antibodies due to the often-expedited review process. These non-standard methods and reduced timelines can put pressure on the optimization of the development process. Establishing a manufacturing plan early, well before Phase 3 studies, can help alleviate the pressure and help avoid potential delays.
A manufacturing plan can help with the following:
- Locking down processes before GMP production
- Avoiding delays and CMC issues
- Fulfilling FDA expectations
For help in understanding the FDA expectations, referencing their guidance documents that include the CMC information for drug substance and drug product that should be included in IND applications is the key2. Changes made during the development stages are submitted by amendments to the applications, sometimes prior to implementation. Working with a partner with late-stage and commercial manufacturing experience can not only help solidify the processes, but also guide developers through the regulatory pathway.
In addition to the manufacturing of drug substance and drug product, preparing for the clinical supply, including labeling, packaging and delivery, should be considered during the initial phase of development as well. Consideration must be given to FDA expectations regarding handling of the product at the clinical trial site. The right partner can provide a smooth transition from the manufacturing and vialing of gene therapies to their labeling, packaging, and storage. Additionally, they can help map out supply chain needs to get the gene therapies to the clinical trial locations when ready.
Catalent is the right partner to guide you through the fast-paced gene therapy timeline. Catalent Cell & Gene Therapy, with over 30 years of clinical and commercial development and manufacturing experience for gene therapies including an FDA-licensed commercial facility, has the expertise to help develop a robust, scalable manufacturing process that will meet CMC requirements. Catalent Clinical Supply Services support planning and forecasting, packaging solutions, distribution and logistics for clinical trials. Our regulatory experience, including successful inspections, can help our partners avoid delays due to CMC issues and clinical supply. Together, the Catalent team provides a smooth transition from manufacturing to delivering the gene therapies to the clinic.