Proteins & Peptides Comparability Studies

During the manufacturing of protein/peptide therapeutic products, it is often necessary to optimize the manufacturing process to ensure the quality of the final product. Comparability studies are key to ensuring that changes in manufacturing processes or formulation conditions don't adversely affect the quality, safety, and efficacy of protein/peptide therapeutic products. CD Formulation conducts comparability studies on protein/peptide therapeutics based on the principles of the ICH Q5E guidelines for comparability of biotechnology/biological products, including characterization of physicochemical properties, conformation, immunogenicity, potency, and biological activity.

Purpose of Comparability Studies

The purpose of conducting a comparability study of two biological products is to determine that there are no significant differences in the efficacy and safety (clinical properties) of the two biological products, despite known differences in their production sources.

The ICH Q5E Biotechnology/Biological Product Comparability Guideline states: "Demonstration of comparability does not necessarily mean that the quality attributes of the products before and after the change are the same, but rather that they are highly similar and that current knowledge is sufficiently predictive to ensure that any differences in quality attributes will not adversely affect the safety or effectiveness of the drug product."

According to the principles of the ICH Q5E guideline, comparability studies should provide detailed analytical confirmation that the product quality and degradation of the drug product before and after the manufacturing process change have not deteriorated quantitatively or even qualitatively. If analytical characterization and nonclinical comparability studies are not sufficient to meet this requirement, the ICH guideline Q5E requires additional clinical comparability studies.

Fig. 1 Summary of step-wise nature of studies performed in a typical comparability assessment of a protein-based drug candidate. (Alsenaidy MA, et al., 2014)

Explore Our Proteins & Peptides Comparability Study Services

Due to the complexity of protein/peptide biopharmaceuticals, implementing a comprehensive, robust comparability study program requires a great deal of scientific knowledge and experience. At CD Formulation, our comparability study team deploys customized analytical strategies combining a variety of analytical techniques for comparability studies of your product's physicochemical properties, higher-order structure, stability profile, and immunogenicity.

Our comparability study programs include all relevant quality attributes involved in evaluating your protein/peptide therapeutics, from analytical testing, and bioassays (in vitro or in vivo) to animal pharmacokinetics and/or pharmacodynamics and toxicity assessments to support your manufacturing process changes.

Our laboratory has a broad technology base that enables us to provide high-resolution, accurate mass (HRAM) data. Based on many years of experience, we have developed a series of comparability study plans, including but not limited to:

Protein/Peptide Physicochemical Characterization

We select protein analyses referenced by the ICH Q6B guideline to scrutinize the product from all aspects, including structural features (including primary, secondary, and higher-order structures) and evaluation of post-translational modifications (PTMs), glycosylation, physicochemical properties, bioactivity/potency, and immunogenicity to demonstrate that modifications that could adversely affect drug safety and efficacy have not occurred. We also evaluate the purity/impurity profile and compare it to GLP or cGMP standards.

Protein/Peptide Bioactivity Assay

We use in vitro binding assays and functional bioassays to determine the bioactivity of protein/peptide therapeutics.

Protein/Peptide Stability Profile Assessment

We perform a set of forced degradation studies and accelerated stability studies to characterize the stability of protein drugs in accordance with ICH guidelines.

1) Forced degradation studies: These studies are used to elucidate the physicochemical mechanisms of protein degradation and we offer:

• Hydrolysis (exposure to acidic, and alkaline).
• Oxidation (oxidizing stresses).
• Photolytic (exposure to light).
• Thermal (exposure to heat).

2) Accelerated stability studies: These are used to measure the rate of a given degradation process over time at different temperatures in a specific formulation and primary container.

Protein/Peptide Immunogenicity Assays

Our senior scientists use a multi-layered screening approach to measure anti-drug antibodies (ADA) and neutralizing antibodies NAbs to assess the immunogenicity of therapeutic proteins and peptides, helping our clients obtain rigorous data.

Protein/Peptide Non-clinical Pharmacokinetic Assessment

Changes in the glycosylation pattern, charge distribution, and aggregation properties of a protein during the manufacturing process may have a measurable effect on its pharmacokinetic properties, which may or may not have an impact on the pharmacodynamics, efficacy, and safety of the drug.

Our scientists use animal models (rodents or primates) to evaluate the pharmacokinetic profile of protein drugs. These pharmacokinetic studies are conducted using the same route of administration and dosing regimen, providing comparative results (e.g., absorption, bioavailability, clearance, and elimination half-life) that should be very similar for the two samples being compared.

Why Choose Us for Proteins & Peptides Comparability Studies？

• Our team of scientists and researchers have extensive experience in conducting protein and peptide comparability studies.
• We have cutting-edge equipment and facilities that allow us to perform a wide range of analytical and biochemical assays to assess the comparability of proteins and peptides.
• We understand that every project is unique, and we work closely with our clients to develop customized study designs and protocols to meet their specific needs and requirements.
• We offer integrated analytical procedures to demonstrate the similarity of your product to a reference product.
• We offer flexible testing options to meet your diverse research needs.

Publication

As a leading global provider of protein/peptide biologics comparability studies, CD Formulation applies detailed analytical knowledge to evaluate the critical quality attributes of your protein therapeutic products throughout your product development lifecycle, from early to late development and ongoing manufacturing, to help you ensure that manufacturing process changes do not affect product quality, efficacy or safety and meet regulatory requirements. Please feel free to contact us if you are interested in our services.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.