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Critical Quality Attribute Characterization Service

Introduction Critical Quality Attribute Characterization Workflow What We Can Offer FAQ

Introduction

mRNA therapeutics demand focus on Critical Quality Attributes (CQAs)—mRNA purity (integrity, cap efficiency, low dsRNA) and LNP physicochemical properties (size, charge, entrapment efficiency)—to ensure protein expression and regulatory compliance.

Creative Biolabs' Custom CQA Characterization Service streamlines trials via advanced LNP analytics, delivers robust data for proof-of-concept to IND studies, and offers customized protocols for formulation stability, efficacy, and risks.

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Critical Quality Attribute Characterization Service

The reliable characterization of LNP-mRNA CQAs requires a tailored suite of advanced analytical methods, each designed to isolate and quantify a specific property.

LNP Physicochemical CQAs

  • Particle Size and Polydispersity:
    • Method: Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA).
    • Core Detection Indicator: Hydrodynamic diameter (nm) and Polydispersity Index (PDI).
  • Surface Charge (Zeta Potential):
    • Method: Micro-electrophoresis.
    • Core Detection Indicator: Zeta Potential (mV). A controlled, near-neutral surface charge is essential for stability and biological interaction.
  • Morphology:
    • Method: Cryo-Electron Microscopy (Cryo-TEM).
    • Core Detection Indicator: Visual confirmation of spherical integrity, homogeneity, and ruling out the presence of aggregates or non-LNP colloidal structures.

Functional and Purity CQAs (LNP and mRNA)

  • Entrapment Efficiency (EE):
    • Method: Chromatographic separation (e.g., SEC-HPLC) or ultracentrifugation followed by spectrophotometric quantification of free versus encapsulated mRNA.
    • Core Detection Indicator: Percentage of mRNA entrapped. High EE is critical for maximizing drug potency.
  • mRNA Purity and Integrity (PI):
    • Method: Capillary Electrophoresis (CE) and high-resolution Liquid Chromatography (LC).
    • Core Detection Indicator: Percentage of full-length transcript and quantification of truncated species.
  • Immunogenic Impurities:
    • Method: Specialized analytical assays to detect and quantify double-stranded RNA (dsRNA) and residual process components (e.g., template DNA, host cell proteins).
    • Core Detection Indicator: Concentration of dsRNA (ng/μg mRNA).

Bioperformance and Safety CQAs

  • In Vitro Drug Release Kinetics:
    • Method: Continuous Flow (CF) systems or customized dialysis methods mimicking physiological conditions (pH, temperature).
    • Core Detection Indicator: Cumulative drug release percentage over time, providing a model for in vivo retention and release profiles.
  • Cytotoxicity:
    • Method: Tetrazolium salt assays (e.g., MTT, MTS) or luminescence-based assays on target cell lines.
    • Core Detection Indicator: Cell viability percentage compared to control, essential for de-risking dose-limiting toxicity.

Workflow

Our comprehensive, client-centric workflow is designed for maximum clarity and scientific rigor, ensuring all critical development questions are answered with verifiable data.

Required Starting Materials

  • LNP Formulation Composition and Preparation Protocol
  • IVT mRNA Transcript Information
  • Target Therapeutic Application/Target Cell Line
Materials
Project Scoping

Project Scoping & Material Receipt

Detailed review of client-provided materials, definition of CQA acceptance criteria, and establishment of the customized analytical plan.

Physicochemical Characterization

Non-destructive testing to determine particle size (hydrodynamic diameter), polydispersity index (PDI), and zeta potential. Morphological analysis confirms structural integrity and homogeneity.

Physicochemical
Functional Quality

Functional Quality Testing (mRNA Cargo)

Assessment of mRNA Purity and Integrity (PI) via CE, and quantification of residual contaminants (e.g., immunogenic dsRNA) via specialized high-resolution chromatography.

Predictive Bio-performance Assays

Determination of EE using separation techniques, and assessment of In Vitro Drug Release kinetics using advanced methods (e.g., Continuous Flow systems). Cellular compatibility is verified via the MTT cytotoxicity assay.

Bio-performance
Data Analysis

Data Analysis & Reporting

Statistical analysis of all raw data, comparison against acceptance criteria, and professional interpretation by our senior scientific team.

Final Deliverables

  • Comprehensive CQA Report
  • Batch-to-Batch Comparability Data
  • Optimized LNP Formulation Parameters
Deliverables
Data Analysis

Estimated Timeframe

The typical timeframe for this service ranges from 6 to 12 weeks, depending on the complexity of the client's LNP formulation, the scope of required testing (e.g., inclusion of full stability studies), and the number of batches submitted for analysis.

What We Can Offer

As a leading provider in advanced biopharmaceutical analytics, Creative Biolabs delivers tailored, robust solutions that eliminate the guesswork from your mRNA development program. We don't just provide data; we provide the scientific certainty required for regulatory success. Our services are flexible, customizable, and backed by two decades of nucleic acid expertise.

Customized Analytical Panels
Flexible, client-defined CQA panels tailored to your therapeutic modality (e.g., oncology, infectious disease) and developmental phase (pre-clinical to Phase Ⅰ/Ⅱ).

Advanced LNP Physicochemical Mastery
Precision characterization of key LNP attributes (Particle Size, PDI, Zeta Potential, Cryo-TEM-verified Morphology) via state-of-the-art tools to ensure colloidal stability.

Predictive Functional Bioperformance
Highly sensitive EE methods and dynamic CF In Vitro Release models for better predictability than static assays.

Gold-Standard mRNA Purity Analysis
Comprehensive quantification of mRNA Integrity, Capping Efficiency, and dsRNA (via high-resolution CE/chromatography) to ensure low immunogenicity.

Regulatory-Grade Documentation
Compliance with a robust Quality Management System (QMS) to meet IND submission requirements for analytical report/procedure quality and technical rigor.

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Customer Reviews

  • Enhancing LNP Stability and Solidifying Frozen Storage Protocols: "After adopting Creative Biolabs' Custom Critical Quality Attribute Characterization Service in our research, our confidence in frozen storage protocols has significantly increased. Their detailed analysis of zeta potential and aggregation kinetics provided the necessary concrete data to finalize our formulation buffer."

    —Daniel Czerny (2 months ago)

  • Accurate dsRNA Clearance to Advance mRNA Purification Strategy Optimization: "The assessment from Creative Biolabs' Custom Critical Quality Attribute Characterization Service helped us achieve a key adjustment in our mRNA purification strategy. Their quantification of double-stranded RNA (dsRNA) contaminants was crucial for reducing the inflammatory risk of our therapy, allowing us to proceed with high-dose in vivo studies."

    — Emma Kler (Last week)

  • Predicting Drug Release Kinetics to Accelerate Formulation Optimization: "The comparative analysis of in vitro drug release provided by Creative Biolabs' Custom Critical Quality Attribute Characterization Service was highly valuable. Compared with traditional static dialysis methods, the dynamic continuous flow model they used could more accurately predict the performance of our LNPs, saving us valuable time in formulation refinement."

    — Jen Sith (4 months ago)

FAQs

How does Creative Biolabs' service help us avoid the common problem of in vivo LNP aggregation?

We focus heavily on Surface Charge (Zeta Potential) and PDI during our characterization. A tightly controlled PDI and optimized Zeta Potential ensure strong colloidal stability, which is the primary defense against aggregation both during storage and upon systemic administration. We recommend discussing our stability study protocols during your consultation.

Why is Creative Biolabs' In Vitro Drug Release data more predictive than standard dialysis methods?

We leverage dynamic CF systems and specialized separation techniques. Standard static dialysis often fails to mimic the biological environment accurately. Our dynamic CF models simulate systemic circulation and dilution, providing release data that is much more representative of how your LNP will behave in vivo.

We use a modified nucleoside (e.g., Pseudouridine). Can your Purity analysis distinguish between modified and non-modified contaminants?

Yes. Our high-resolution chromatographic methods are optimized to resolve complex oligonucleotide mixtures. We can accurately assess the integrity of the modified transcript and precisely quantify known and unknown impurities, including those derived from the use of modified nucleosides.

The Custom Critical Quality Attribute Characterization Service by Creative Biolabs is your indispensable tool for transforming ambitious mRNA concepts into safe, stable, and efficacious therapeutic candidates. We provide the essential quality data and scientific insights needed to de-risk development, accelerate regulatory approval, and maximize the commercial potential of your drug product.

Contact Our Team for More Information and to Discuss Your Project

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.