Subjects

• Drug regulation
• Recombinant protein therapy

To the Editor:

Since the first marketing approvals of recombinant biopharmaceuticals, the question of which changes in quality attributes, which comprise identity, strength and purity, are acceptable in the life cycle of these products without changing the product label has been debated extensively¹. This question is especially important in the context of manufacturing process changes, which happen quite frequently and for various reasons (e.g., process improvements, scale changes or site transfers). Although companies and health authorities have been managing these quality changes for many years based on the principle that changes in quality attributes can be accepted only if they do not alter safety and efficacy, the lack of peer-reviewed data in the public domain has limited debates about product quality and variation to a discussion of principles rather than specifics. Here, we present a study that looks at variation in three major marketed biologics, the purpose of which is to provide more transparency and to anchor the debate about acceptable changes in quality attributes on a firmer factual footing. Identifying such variations in quality attributes could help not only biotech companies in their development efforts but also the medical and scientific communities in understanding these products. By analyzing the quality profiles of the glycosylated recombinant therapeutic proteins Aranesp (darbepoetin alfa), Rituxan/Mabthera (rituximab) and Enbrel (etanercept) sourced from the market between 2007 and 2010, our data thus provide examples of acceptable variations for products that have remained on the market with unchanged product labels.

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