Background The term “intended copy” (IC) is used to describe biotherapeutic medicinal products that have not been approved via a regulatory pathway aligned with WHO's Similar Biotherapeutic Product (SBP) guidelines to ensure quality, safety and efficacy. In some countries, the WHO SBP guidelines are not being consistently adopted or implemented and ICs of etanercept (ETN), originally developed by Pfizer (Wyeth), are being marketed as biosimilar versions, although rigorous regulatory criteria for analytical testing and clinical demonstration of biosimilarity may not have been fully assessed.

Objectives Pfizer conducted an analytical assessment of multiple lots of 4 ICs, and a single lot of 1 IC of ETN that have received marketing approval in various global markets. The results for critical quality attributes are compared with the licensed specifications of ETN.

Methods ICs of ETN manufactured by Shanghai CP Guojian (China), Lafrancol (Colombia), Cipla (India), Probiomed (Mexico) and AryoGen (Iran) were assessed. Analyses included a subset of the release tests for ETN, together with evaluation by additional characterization methods to provide appropriate comparative detail on biochemical composition. Results for each product were evaluated against licensed specifications and historical ranges for ETN and ETN reference standard for the additional characterization test results.

Results None of the ICs met all of the individual product quality criteria that Pfizer apply for analytical comparability, although each product met some of the requirements. Principal differences were observed during assessments of identity (as measured by tryptic peptide map high-performance liquid chromatography [HPLC]), purity (as measured by hydrophobic interaction chromatography [HIC]), degree of aggregation (size exclusion [SE] HPLC), distribution of charged species (isoelectric focusing [IEF]/anion exchange [AEX] chromatography) and carbohydrate profile (N-linked oligosaccharide map). These are shown in the table.

Conclusions While a degree of structural similarity with ETN was observed for each of the ICs analyzed, a number of significant structural and biochemical differences were noted. None of the products analyzed meet the combination of release specification and additional characterization criteria Pfizer typically apply to support a comparability assessment with ETN.

Disclosure of Interest M. Scheinberg Consultant for: Pfizer Boehringer Mannenheim, Genzyme, Orygen, GSK, G. Castaneda Hernandez Consultant for: Abbvie, Bayer, Boehringer-Ingelheim, Eli-Lilly, Laboratorios Liomont, Laboratorios Sophia, Medix, Merck-Serono, Merck, Sharp and Dohme, Novartis, Pfizer, Roche and Sanofi, Speakers bureau: Amgen, Abbvie, Astra-Zeneca, Bayer, Eli-Lilly, Janssen-Cilag, Laboratorios Liomont, Laboratorios Sophia, Medix, Merck-Serono, Merck, Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi and UC, M. Li: None declared, U. R. Rao Consultant for: Pfizer, Sanofi, E. Singh Shareholder of: Pfizer, Employee of: Pfizer, E. Mahgoub Shareholder of: Pfizer, Employee of: Pfizer, J. Coindreau Shareholder of: Pfizer, Employee of: Pfizer, J. O'Brien Shareholder of: Pfizer, Employee of: Pfizer, S. M. Vicik Shareholder of: Pfizer, Employee of: Pfizer, B. Fitzpatrick Shareholder of: Pfizer, Employee of: Pfizer, B. Hassett Shareholder of: Pfizer, Employee of: Pfizer