SGS is pleased to be participating in the AAPS Biotech Conference, May 20-22 in San Diego,  with a poster on analytical characterization of biosimilars. In addition, you can meet with SGS experts at the booth 100. Visit the event page.

If you can’t attend, but are interested in seeing the complete poster, please email us to request a copy.

Poster Presentation

Title: Analytical Characterization of Biosimilar Products to Establish Comparability.

Author: Fiona Greer, SGS M-Scan

Date and Time: May 21, 11:00 a.m. - 6:30 p.m., Poster #T2144

Purpose: Any manufacturer seeking to develop and market a biosimilar product requires comprehensive physicochemical structural characterization of the (glyco)protein. For biosimilar products, this task should be performed at three distinct stages of development. Initially, batches of the target originator molecule should be studied to determine the exact sequence of the target protein, the post-translational modifications and the variability of quality attributes in batches over time. Then, once the biosimilar product is manufactured, characterization needs to be performed to confirm its structure. Finally, manufacturers must provide comparative data for the biosimilar side-by-side with the originator molecule as required by various regulatory guidelines.

Methods: Our poster will detail analytical methods including MALDI-TOF MS, ESI-MS, ESI-MS/MS, GC-MS, HPAEC-PAD, cIEF, CD and AUC which can be used to establish comparative analysis on glycoprotein products and reference various regulatory guidelines in effect. Strategies for primary and higher order structure determination will be discussed particularly for antibodies where the size and complexity of the molecule requires LC/MS/MS approaches.

Results: We will share data obtained by performing multiple orthogonal analyses (using techniques outlined above) to assess their utility in providing a comparative analysis between molecules. The sensitivity of these methods will demonstrate detection of small changes in post-translation modifications such as glycosylation or other differences between the biosimilar and originator molecules. For example, Figure 1 illustrates the use of capillary Isoelectric Focusing (cIEF) to monitor charge states of different batches of antibodies. Secondary structure can be probed using Far-UV Circular Dichroism (CD) to compare various batches of an originator against its biosimilars (Figure 2).

Conclusion: Strategies for comparability must include assessment of primary and higher order structure. Batch-to-batch variation of the product should be determined for both the biosimilar and the originator material. In practice this requires the same types of analytical techniques which may have been used for characterizing the originator molecule, but now they are conducted side-by-side with the biosimilar to compare it with the reference product. In essence, an analytical strategy will follow closely the requirements of the ICH guideline Q6B. This characterization is carried out prior to any clinical assessment of the biosimilar product.

Figure 1. cIEF comparability assessment of three batches of intact antibody product.

Figure 2. Far-UV CD analysis of various batches of originator molecule and biosimilar.