Consulting Services

Development of Analytical Methods

• Purpose: Design and optimize analytical methods to assess critical quality attributes (CQAs) such as identity, purity, potency, and stability.

• Activities:

  • Development of assays for product release, characterization, and process development support.

  • Use of orthogonal techniques (e.g., qPCR, ddPCR, analytical ultracentrifugation [AUC], capillary electrophoresis, cryo-TEM) to ensure comprehensive characterization.

  • Customization for specific modalities, such as viral vectors (e.g., AAV, lentivirus), plasmid DNA, or mRNA-based vaccines.

  • Incorporation of bioassays, including cell-based potency assays, to confirm biological activity.

• Regulatory Alignment: Methods are developed to meet FDA and EMA requirements, including ICH guidelines for validation (e.g., ICH Q2 for analytical method validation).

Characterization of Product and Components

• Purpose: Provide detailed data on the physicochemical and biological properties of the drug substance and drug product.

• Activities:

  • Characterization of viral vectors (e.g., AAV capsid content, full/empty capsid ratios, genome titer, infectious titer).

  • Analysis of mRNA therapeutics for sequence identity, integrity, and impurities (e.g., truncated mRNA, aggregates).

  • Assessment of delivery systems, such as lipid nanoparticles (LNPs) for mRNA vaccines, including lipid content, encapsulation efficiency, and release profiles.

  • Testing of raw materials, starting materials (e.g., master/working cell banks, viral banks), and excipients for purity, identity, and safety.

  • Use of advanced techniques like next-generation sequencing (NGS), bio-layer interferometry (BLI), or mass spectrometry for structural and functional analysis.

Release Testing

• Purpose: Ensure the final product meets predefined specifications for identity, purity, potency, and safety before clinical use.

• Activities:

  • Development and validation of release assays, including:

    • Identity Tests: Confirm product composition (e.g., PCR for vector identity, gel electrophoresis for viral proteins).

    • Purity Tests: Quantify product-related impurities (e.g., empty capsids, host cell proteins) and process-related impurities (e.g., residual DNA, benzonase).

    • Potency Tests: Measure biological activity (e.g., cell-based assays for gene expression or immune response).

    • Safety Tests: Screen for adventitious agents (e.g., mycoplasma, viral contaminants, bioburden) in bulk harvest and purified drug substance.

  • Establishment of product specifications based on robust laboratory data to support IND submission.

  • Validation of release methods to ensure reproducibility and compliance with cGMP requirements.

Stability Testing

• Purpose: Assess the stability of the drug substance and drug product under various conditions to establish shelf life and storage requirements.

• Activities:

  • Design and execution of real-time and accelerated stability studies to evaluate product degradation (e.g., vector integrity, mRNA stability).

  • Analysis of stability-indicating parameters, such as genome titer, infectious titer, and aggregation.

  • Assessment of delivery systems (e.g., LNPs) for stability under storage and transport conditions.

  • Development of stability protocols and reports for inclusion in the IND application.

  • Guidance on container closure systems (e.g., extractables and leachables testing) to ensure compatibility.

Impurity Analysis

• Purpose: Identify and quantify process- and product-related impurities to ensure safety and quality.

• Activities:

  • Detection of residual host cell DNA, proteins, and reagents (e.g., benzonase, Triton X-100) using qPCR, ELISA, or other sensitive methods.

  • Quantification of empty or partial capsids in viral vectors (e.g., via AUC, TEM, or A260/280 ratio).

  • Analysis of mRNA-specific impurities, such as truncated or aggregated mRNA, using capillary gel electrophoresis (CGE) or HPLC.

  • Establishment of impurity thresholds compliant with regulatory guidelines.

Potency Assay Development

• Purpose: Demonstrate the biological activity of the gene therapy or vaccine product to support clinical efficacy.

• Activities:

  • Development of cell-based potency assays to measure gene expression, protein production, or immune response (e.g., neutralizing antibody assays for vaccines).

  • Validation of potency assays to ensure sensitivity, specificity, and linearity as per FDA guidance (e.g., “Potency Tests for Cellular and Gene Therapy Products,” 2011).

  • Alignment with regulatory expectations for phase-appropriate potency testing (e.g., qualification for early-phase trials, full validation for later phases).

Validation of Analytical Methods

• Purpose: Ensure analytical methods are robust, reproducible, and suitable for regulatory submission.

• Activities:

  • Validation of methods for accuracy, precision, specificity, linearity, and range as per ICH Q2 guidelines.

  • Preparation of validation protocols and reports for inclusion in the IND application.

  • Troubleshooting and optimization of methods to address variability or sensitivity issues.

  • Ensuring methods are phase-appropriate (e.g., qualified for early-phase INDs, fully validated for later stages).

Regulatory Compliance and Documentation

• Purpose: Ensure the analytical section meets FDA, EMA, and other global regulatory requirements for IND submission.

• Activities:

  • Preparation of the Chemistry, Manufacturing, and Controls (CMC) section of the IND, including analytical data and method descriptions.

  • Alignment with FDA guidance, such as “Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy INDs” (2020) and “Potency Assurance for Cellular and Gene Therapy Products” (2023).

  • Support for pre-IND meetings with regulatory agencies to discuss analytical strategies and obtain feedback.

  • Authoring and reviewing analytical sections of IND applications, including protocols, reports, and justifications for specifications.

  • Ensuring compliance with cGMP, ICH Q7 (for raw materials), and other relevant guidelines.

Risk Assessment and Quality Control

• Purpose: Identify and mitigate risks associated with analytical methods and product quality.

• Activities:

  • Conducting risk assessments for critical analytical steps to ensure robust quality control.

  • Development of quality management systems (QMS) to support inspection readiness.

  • Monitoring of critical quality attributes (CQAs) throughout the manufacturing process.

  • Implementation of orthogonal techniques to enhance confidence in analytical results.

Support for Novel Technologies

• Purpose: Address analytical challenges specific to emerging modalities, such as mRNA vaccines or gene editing therapies.

• Activities:

  • Development of analytical methods for mRNA therapeutics, including characterization of lipid nanoparticles and mRNA integrity.

  • Support for gene editing therapies (e.g., CRISPR-based) with assays for on-target/off-target effects and genome editing efficiency.

  • Customization of analytical approaches for novel vectors (e.g., non-viral vectors, microbial vectors) or vaccine adjuvants.

Technology Transfer and Scale-Up Support

• Purpose: Ensure analytical methods are transferable and scalable for clinical and commercial manufacturing.

• Activities:

  • Support for technology transfer of analytical methods to contract manufacturing organizations (CMOs) or in-house facilities.

  • Validation of methods at scale to ensure consistency during process scale-up or scale-out.

  • Guidance on analytical method robustness for large-scale production of viral vectors or mRNA vaccines.

Bioanalytical Support for Preclinical and Clinical Studies

• Purpose: Provide analytical data to support preclinical and clinical development, bridging the analytical section with nonclinical/clinical data.

• Activities:

  • Development of bioassays to support pharmacokinetic (PK) and pharmacodynamic (PD) studies.

  • Analysis of biodistribution, shedding, and persistence for gene therapies (e.g., viral vector shedding studies).

  • Support for long-term follow-up (LTFU) studies, including analytical testing for safety and efficacy endpoints.

  • Integration of real-world evidence (RWE) to inform analytical strategies for clinical trials.