Data for regulatory documentation

Enzyme-linked immunosorbent assay (ELISA) is the standard method for monitoring Host Cell Protein (HCP) clearance. To ensure patient safety and product efficacy, the critical reagent of an HCP ELISA, the HCP antibody, must be demonstrated to cover a broad spectrum of the HCPs potentially present in the purified drug substance. However, traditional coverage methods for assessing HCP antibody coverage, such as 2D-Western blot or immunoaffinity-purification combined with 2D gel electrophoresis, are increasingly not sufficient to validate the coverage of an HCP ELISA with regulatory authorities.

Alphalyse's proprietary ELISA-MS™ analysis uniquely combines ELISA-based immunocapture with liquid chromatography mass spectrometry (LC-MS) under native conditions. Using ELISA-MS™, we provide accurate, reproducible data for evaluating and validating your ELISA as required by regulatory authorities.

We can assist you with:

• Performing HCP-ELISA coverage analysis.
• Demonstrating that your HCP-ELISA is fit-for-purpose.
• Verifying ELISA results using orthogonal methods to identify and fully characterize individual HCPs of concern.
• Performing detailed risk assessment and closely monitoring process performance parameters.
• Thorough bridging between new ELISA kits and reagents or process changes.

Developing a process-specific ELISA usually requires 1 - 2 years for antibody development and assay validation. Furthermore, if the HCP coverage of your ELISA is insufficient, you risk delayed regulatory approval due to inadequate impurity detection and clearance.

LC-MS assays require only 6-8 weeks of development for any biologic product, which can significantly accelerate the development, marketing approval, and commercial manufacturing of biopharmaceuticals. Furthermore, a fully validated assay under GMP conditions can be in place within 4-6 months.

LC-MS provides the detailed analytical data needed for developing chemistry, manufacturing, and controls (CMC) and for satisfying regulatory requirements. Our clients have had Investigative New Drug (IND) submissions approved by US and EU regulatory authorities based only on LC-MS data; no time- and resource-consuming ELISA is required. LC-MS-based HCP analysis has also been approved as a release assay under Good Manufacturing Practice (GMP).

You need an IND (Investigational New Drug) application to seek an exemption to administer and dispense investigational drugs, whereas the BLA (Biologics License Application) is a request for permission to introduce a biologic into commerce. The data provided in these documents must fulfill the ICH Q6B guidelines to be accepted by the regulatory authorities.

There has been an increased focus from regulatory authorities on orthogonal data for HCPs using MS since traditional methods for HCP analysis do not allow for characterization of individual high-risk or high-abundance protein impurities. This is particularly concerning for mAb products, which are typically administered to patients with high frequency and concentration, but all drug product development benefits from good patient safety precautions. Regulatory authorities increasingly demand more detailed information about potential risks, and the lack of such data has delayed many projects.

All our analyses are made to fulfill ICH guidelines and can be submitted as part of regulatory documentation. Our clients routinely use the data for INDs, BLAs, and for moving through the clinical phases. You receive the data in easy-to-understand reports, and all raw data can be supplied in Excel sheets and mass spec formats if needed.