As a medicinal chemist with experience in large pharmaceutical companies, I’ve spent my career designing and optimizing drug candidates. But when I was tasked with advancing a highly potent cytotoxic peptide-drug conjugate (PDC) toward IND submission, I found myself in uncharted territory. While I had expertise in chemistry and drug design, I had limited experience with pre-clinical studies and a minimal understanding of the regulatory requirements for the CMC (Chemistry, Manufacturing, and Controls) section of the IND.
The scale-up required to transition from a 50 mg drug substance to over 200 grams of cGMP material for use in preclinical studies was daunting, especially considering the complexity of the molecule. We had to source peptide, linker, and warhead components reliably and identify the right partners to handle specialized processes like lyophilization and high-quality HPLC purification.
Given the urgency of our project, we had no time to waste. Our goal was clear: we needed to move as quickly as possible toward the IND submission. Fortunately, we had already partnered with Syner-G BioPharma Group, and their support proved invaluable in helping us navigate the entire process.
Why Syner-G Was the Key to Success
Syner-G’s expertise provided the guidance and resources necessary to meet the complex regulatory and scientific challenges we faced. Here’s how they helped us successfully scale our cytotoxic peptide-drug conjugate:
- Vendor Selection and Oversight: One of our immediate needs was identifying a vendor capable of handling the scale-up and ensuring the lyophilization and HPLC purification processes met our cGMP standards. Syner-G worked with us to find the right partners and facilitated the oversight necessary to keep the project on track.
- Creating High-Quality RFPs and Vetting Proposals: With a small team of two people handling both scale-up and discovery programs, crafting high-quality RFPs was critical to ensuring we selected the right vendors and partners. Syner-G provided coaching on how to structure these documents and vet the proposals effectively, ensuring we found the best match for our needs.
- Navigating Regulatory Requirements for CMC: With limited experience in regulatory affairs, we needed expert guidance to navigate the CMC section of the IND. Syner-G’s team coached us on how to present the data and processes in a way that aligned with FDA requirements, helping us avoid costly delays and ensuring our IND submission would be as robust as possible.
- Data Interpretation and Risk Management: As the data started coming in from our vendors, Syner-G helped us interpret it, focusing on real challenges versus issues that could be managed within existing data. Their experience helped us manage risk and prioritize tasks effectively, ensuring we didn’t waste time on problems that weren’t critical to our timeline.
A Successful Outcome: 250g of cGMP Drug Substance Delivered
Thanks to Syner-G’s support and guidance, we were able to successfully scale up from 50 mg to 250 grams of cGMP drug substance and produce 2,000 drug product vials for the IND submission and First-In-Human (FIH) study, all within just under 15 months from candidate nomination.
This achievement would have been impossible without the expertise provided by Syner-G in the critical areas of regulatory compliance, vendor management, and data interpretation. Their team was an extension of ours, helping us move faster and more efficiently than we ever could have done alone.
Key Takeaways for Fellow Scientists
- Start Early on CMC Planning: Scaling up drug substance from milligrams to grams is a massive task. Ensure you have a clear CMC plan in place early to avoid delays.
- Seek Expert Help When Needed: If you’re in unfamiliar territory with regulatory requirements or complex scale-up processes, don’t hesitate to partner with experts who can guide you through the maze.
- Craft High-Quality RFPs: The strength of your RFPs and your ability to vet vendors will directly impact the quality and speed of your program.
- Data Interpretation is Critical: Having the right guidance to interpret data and manage risk effectively can save valuable time and resources during the development process.
Thanks to the support of Syner-G experts, we’ve successfully navigated the challenges of scaling up a cytotoxic peptide-drug conjugate and are well on our way to clinical trials. For anyone facing a similar path, I can’t stress enough the importance of building strong partnerships and ensuring you have the expertise needed at every step of the journey.
