Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

A robust raw material qualification program is foundational to any successful viral vector Chemistry, Manufacturing, and Controls (CMC) strategy. For biotech sponsors in the UK, variability in raw materials like plasmid DNA and ancillary reagents can impact clinical timelines and MHRA submissions. This asset outlines the framework for managing the supply chain through supplier audits, multi-lot testing, and phase-appropriate qualification to support the consistency, purity, and performance of AAV, lentiviral, and adenoviral vectors intended for clinical evaluation. Franklin Biolabs provides the analytical infrastructure and regulatory experience to establish this control.

Establishing a Resilient CMC Supply Chain

The transition from research-scale vector production to a process suitable for clinical trials requires a systematic approach to controlling all sources of variability. A significant number of process failures can be traced back to inconsistencies in raw materials. Establishing a well-documented raw material control strategy is a prerequisite for a successful IMPD submission and subsequent clinical trial authorization from the MHRA.

A successful strategy depends on a deep understanding of how each component, from the master plasmid DNA to the cell culture media, influences the final vector’s quality attributes. A certificate of analysis alone is insufficient to establish this level of process control.

Learn more about how Franklin Biolabs optimizes manufacturing processes by viewing the full video .

Plasmid DNA: The Genetic Starting Point

The quality of plasmid DNA used in transient transfection systems for AAV or lentivirus production directly dictates the consistency of the output. We implement a phase-appropriate strategy for plasmid qualification.

• Supplier Vetting: We conduct technical audits of plasmid suppliers to ensure their manufacturing processes, quality control, and documentation meet GxP standards.

• Analytical Characterization: Each new lot of plasmid is subjected to a panel of analytical tests, including identity confirmation (restriction digest, sequencing), purity assessment (A260/280, gel electrophoresis), and quantification.

• Functional Verification: The ultimate test is performance. We confirm the plasmid’s ability to generate high-titer, high-quality viral vectors in small-scale engineering runs before committing it to a large-scale production batch.

Ancillary Material and Reagent Controls

The complex biological systems used for viral vector production are sensitive to minor changes in ancillary materials like media, sera, and buffers. A proactive qualification program mitigates this risk. The goal is to ensure that a change in a raw material lot number does not result in a change to the final vector product. This control is vital for demonstrating process consistency to regulators.

Achieving sustained transgene expression, as seen in AAV clinical trials, depends on a highly pure and consistent vector product (PMID: 19706466). Similarly, minimizing toxicity is a key objective for all gene therapies, and controlling for impurities from raw materials is a direct way to support a favorable safety profile (PMID: 14977858). A robust qualification program ensures that the materials used do not introduce contaminants that could compromise these clinical outcomes.

Our >100,000 sq ft facility is equipped with the analytical platforms needed to qualify these materials, supporting an 18-24 month timeline to get candidates to IND. While the Franklin Biolabs brand launched in 2024, our scientific leadership has maintained a 100% successful IND rate since 2019. This rigorous approach to material science is a key component of that record.

This page provides an overview of our approach. For a deeper discussion on scaling your AAV program, please see our parent page on Large-Scale AAV Manufacturing and Process Development.