Ask the Expert: Lilia Bi, MD, PhD

RareMoon’s CMC Expert Offers Her Insights

What are you most excited about in your new role at RareMoon?

I feel incredibly honored and rewarded with my current role as a CMC consultant for cell and gene therapies at RareMoon. This role provides me with opportunities to impact the innovation of an exciting area to treat potential diseases. Many factors need to be considered to ensure the products meet regulatory standards and are manufactured consistently and safely. During the early study stage, the key factors may include product design, starting material control, drug substance manufacturing, final product fill and vial, proper stability study plan, etc. However, when reaching the late study stage, the key consideration should move to explore critical quality attributes (CQAs), refinement of critical process parameters (CPP), and compliance with full cGMP. By the time the Sponsor files a BLA, all manufacturing processes and analytical methods should be validated. At RareMoon, I have the opportunity to support our clients with planning ahead, which is the most important thing for CMC, to avoid unnecessary “winding road.”

How could gene therapy manufacturers and Sponsors best utilize your regulatory and scientific expertise?

As a senior CMC consultant with 20 years’ experience in evaluating and reviewing the CMC submissions of various gene therapy products, our clients can use my experience at different product development stages.

My experience includes advising on stage-appropriate CMC requirements for INTERACT, pre-IND, and EOP2 meetings, as well as INDs, BLA, and post-approval submissions. My familiarity with the CMC content is helpful to our clients at an early submission stage, with my review experience of more than one hundred CMC Module 3 submissions, which could be used for an IND client. I have also participated in two AAV BLA reviews and had inspection experience as a product reviewer.

What advice would you give to a sponsor manufacturing a gene therapy at an early stage (Pre-IND) of development?

There are many benefits to contacting the FDA early via pre-IND meetings. One of them is to obtain the FDA’s comments that will assist sponsors in submitting a complete IND application. From CMC’s perspective, the meeting package includes but is not limited to a description of the product, discussion of control of materials, description of manufacturing processes for drug substance and drug product and the in-processing controls, proposed lot release tests for drug substance and drug product, proposed stability study plan, description of product formulation and storage condition, potency development plan, description of delivery device for product, etc. Regarding the CMC questions, I recommend asking clear, focused questions so the Agency can provide advice on the targeted question. Since the maximum number of questions is limited, sponsors should consider the most critical questions for their specific stage-appropriate development across all three categories, including preclinical and clinical.