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Characterizing Leachables and Extractables for Next-Generation Therapies

PROVEN INTELLIGENCE ACCELERATING NEXT-GENERATION THERAPIES

Characterizing Leachables and Extractables for Next-Generation Therapies

CELL & GENE | RNA | BIOLOGICS

Proven Intelligence in CMC Analytics.

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Frequently Asked Questions

What are the primary risks of leachables and extractables in AAV drug products for MHRA submissions?

For MHRA and other global regulatory submissions, the primary risks involve patient safety and product stability. Leachables from single-use manufacturing components or final container-closure systems can introduce impurities that may be immunogenic or toxic. For AAV vectors, certain compounds can also induce capsid aggregation or denaturation, compromising product potency and leading to delays in Investigational Medicinal Product Dossier (IMPD) approvals.

How does an E&L testing strategy differ between viral vectors and lipid nanoparticle (LNP) therapy systems?

The strategy must be tailored to the modality. For AAV viral vectors, the focus is on protein-surface interactions and leachables from filters and bags that could affect capsid integrity. For an LNP therapy, the lipid components themselves can interact with or extract plasticizers from manufacturing materials. The analytical strategy for LNPs must also account for potential degradation products of the lipid excipients, which present a different risk profile than protein-based vectors.

What analytical techniques are required for a comprehensive E&L profile under GxP conditions?

A comprehensive profile requires orthogonal analytical methods to detect and quantify a wide range of potential organic and inorganic compounds. This typically includes Liquid Chromatography-Mass Spectrometry (LC-MS) for non-volatile compounds, Gas Chromatography-Mass Spectrometry (GC-MS) for volatile and semi-volatile organics, and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for elemental impurities. All methods must be appropriately qualified for use in GxP conditions.

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Executive Summary

A robust extractables and leachables (E&L) program is a foundational component of any successful CMC strategy for next-generation therapies. The unique biochemical properties of AAV vectors, LNP-RNA complexes, and cell-based constructs demand a testing approach that moves beyond legacy templates. An effective E&L analysis identifies and quantifies potentially harmful impurities that migrate from manufacturing equipment, delivery devices, and container-closure systems into the final drug product. Proactively managing these risks is integral to ensuring patient safety, maintaining product stability, and meeting the stringent requirements of global regulators, including the MHRA and FDA.

Tailored E&L Programs for Complex Modalities

The materials used in the bioprocessing and storage of next-generation therapies present unique interaction risks. A one-size-fits-all E&L program is insufficient for these complex products.

  • AAV Vectors: The proteinaceous AAV capsid is susceptible to interactions with leachables that can promote aggregation or affect surface charge, potentially altering infectivity and immunogenicity.

  • LNP/RNA Systems: The lipid components in LNP formulations can extract plasticizers and other compounds from single-use systems. This risk profile is distinct from protein-based products and requires specialized analytical consideration, drawing on experience from programs like the Moderna collaboration.

  • Cell-Based Modalities: The viability and function of CAR-T or stem cell therapeutics can be compromised by cytotoxic leachables, demanding highly sensitive detection methods.

Our approach is built on a scientific, risk-based assessment tailored to your specific vector or cell type, manufacturing process, and final container system. This ensures the analytical program is both comprehensive and efficient, generating the precise data needed for IMPD and IND submissions.

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A History of Analytical Rigor

Franklin Biolabs was formally launched in 2024, but our core scientific team’s track record in bringing complex therapies to the clinic is extensive. This history includes a 100% successful IND rate since 2019, achieved by integrating deep analytical expertise directly into preclinical program design. Our team’s experience in advancing AAV candidates with favorable safety profiles (PMID: 35333110) underscores the importance of rigorous product characterization, including E&L analysis, from the earliest stages. By identifying potential issues long before pivotal studies, we help sponsors maintain an 18-24 month timeline to IND.

Our analytical laboratories, housed within our >100,000 sq ft facility, are equipped to perform these sensitive assays under GxP conditions. We develop and qualify methods that align with harmonized international guidelines (ICH), ensuring your data package is suitable for multi-jurisdictional review.

This analytical foundation is a key component of the services provided within our Vector | CMC | Analytics Services pillar.

Scientific Process Diagram

This content is for informational purposes. For guidance specific to your therapeutic program, please contact our team for a consultation.

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