Protein analysis for comparability

Process performance qualification (PPQ) runs are essential for confirming the process design and demonstrating process robustness before commercial-scale production. EMA and FDA regulations for process validation require that drug products are produced with high batch uniformity, demonstrating process reproducibility and manufacturing control.

Traditionally, you perform PPQ runs after concluding product development. However, we recommend our comparability package for all occasions when you need to understand potential sources of batch variation. This package includes a side-by-side characterization of the drug substance or product samples from different phases or batches to determine intra-batch homogeneity and inter-batch consistency. Clients may also ask us to validate the method and analyze production scale batches so that they can include the data in their biologics license application (BLA) submissions.

Any changes to the chemistry, manufacturing, and controls (CMC) of products in approved marketing applications require new comparability testing to document the implications of these changes. Before distributing a product, you must assess the effects of any post-approval CMC changes for the potential impacts on its safety or efficacy.

How can you obtain accurate documentation quickly if you suddenly need it? With an automated setup, mass spectrometry (LC-MS) allows you to assess samples from various purification steps quickly. The high sensitivity of LC-MS enables the quantification of individual proteins at low ppm levels.

Detailed LC-MS-based comparability and product characterization can facilitate a faster review and approval of CMC changes by the regulatory authorities, moving the product into distribution sooner.

Before approving a biosimilar, regulatory authorities must be convinced that it is highly similar to its originator. They will ask that existing knowledge is sufficiently predictive to ensure that any differences in quality attributes between the originator and biosimilar have no adverse impact on the safety or efficacy of the drug product.

You can document biosimilar and originator comparability through analytical testing, biological assays, and nonclinical and clinical data. However, if analytical studies alone can assure comparability, nonclinical or clinical studies of the biosimilar product are not warranted – saving significant time and resources.

Our reproducible and quantitative LC-MS-based analyses provide detailed data on the protein amounts, product-related variants with post-translational modifications, sequence truncations, and process-related impurities. The results help you document that your biosimilar resembles the originator product closely and complies with the same strict regulatory criteria.