Reverse-Engineering a Blockbuster Biologic | Biosimilar Reference Product Characterization

Before a biosimilar program has a cell line or a process, it has a shopping list. The first thing the team buys is the brand product itself, lot after lot, over several years. In this video, Raghuvirsinh Parmar, PhD, Director Scientific Affairs at ResolveMass Laboratories, explains how biosimilar developers reverse-engineer a blockbuster biologic through reference product characterization, and why this first step shapes everything that comes after it. You get the vial, not the recipe. The originator's cell line, process settings and internal specifications all stay private, so every fact about the molecule has to be measured from the commercial product. We walk through the orthogonal analytical toolbox, the reference lot sourcing plan that FDA expects, how attributes are ranked by risk, and how reference data becomes the quality target for your biosimilar. In this video you will learn: ✔ Why reference product characterization is the real start of biosimilar development ✔ The orthogonal methods used: intact mass, peptide mapping by LC-MS/MS, disulfide mapping, CD, FTIR, HDX-MS, N-glycan, charge variant, aggregate and functional assays ✔ What FDA's September 2025 final guidance on comparative analytical assessment recommends: at least 10 reference product lots spanning several years of expiry, and at least 6 to 10 biosimilar lots ✔ How a risk assessment tool ranks quality attributes, and how quality ranges (mean ± X SD) are set ✔ Why you should aim your process at the centre of the reference range, not the edge ✔ The hardest attributes to match: Fc glycosylation (afucosylation and ADCC, high mannose and clearance), charge variants, and aggregates / higher order structure ✔ The real starting sequence of a biosimilar program, and why analytical work now carries even more weight ⏱ Chapters 0:00 Introduction: the biosimilar shopping list 1:14 You get the vial, not the recipe 2:07 Reference product characterization 3:17 One vial is not enough: reference lot sourcing 4:08 Rank every attribute by risk 5:21 From reference data to a target (QTPP) 6:13 The hardest attributes to match 7:15 Where biosimilar development really begins 8:19 Key takeaways 8:47 Working with ResolveMass 🔬 About ResolveMass Laboratories ResolveMass Laboratories Inc. is a Canadian analytical chemistry and regulatory science partner. We support small and mid-sized pharma and biotech teams with reference product characterization, glycan and charge variant analysis, and comparative analytical assessment, from the first reference lot through submission. 💬 How many reference lots are in your plan? Tell us in the comments. 👍 If this helped, like the video and subscribe for more biologics CMC content. Disclaimer: This video is for educational purposes only and does not constitute regulatory or legal advice. Always refer to the current FDA guidance documents for your specific program. #Biosimilars #BiosimilarDevelopment #ReferenceProductCharacterization #AnalyticalSimilarity #FDAGuidance #Biologics #MonoclonalAntibodies #Glycosylation #CMC #ResolveMass biosimilar development, reference product characterization, biosimilar analytical similarity, comparative analytical assessment, FDA biosimilar guidance 2025, reverse engineering biologics, biosimilar reference lots, quality range biosimilar, biosimilar QTPP, Fc glycosylation, afucosylation ADCC, charge variants, higher order structure, orthogonal methods, peptide mapping LC-MS/MS, HDX-MS, monoclonal antibody characterization, biologics CMC, ResolveMass