Maintaining consistent quality and clinical performance of biopharmaceuticals

Abstract

Biopharmaceuticals are large protein based drugs which are heterogeneous by nature due to post translational modifications resulting from cellular production, processing and storage. Changes in the abundance of different variants over time are inherent to biopharmaceuticals due to their sensitivity to subtle process differences and the necessity for regular manufacturing changes. Product variability must thus be carefully controlled to ensure that it does not result in changes in safety or efficacy. Areas covered: The focus of this manuscript is to provide improved understanding of the science and strategies used to maintain the quality and clinical performance of biopharmaceuticals, including biosimilars, throughout their lifecycle. This review summarizes rare historical instances where clinically relevant changes have occurred, defined here as clinical drift, and discusses modern tools used to prevent such changes, including improved analytics, quality systems and regulatory frameworks. Expert opinion: Despite their size complexity and heterogeneity, modern analytics, manufacturing quality systems and comparability requirements for the evaluation of manufacturing changes cumulatively help to ensure the consistent quality and clinical performance of biopharmaceuticals throughout their product lifecycle. Physicians and patients can expect the same safety and efficacy from biopharmaceuticals and their respective biosimilars irrespective of batch or production history.

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

“…Therefore, in comparison to other isolation methods TFF is more suitable for clinical use, despite not being able to separate different types of biological nanoparticles, resulting in a heterogeneous product. In fact, from a regulatory perspective, the batch‐to‐batch consistency of the product is more important than the heterogeneity 29…”

Batch-to-Batch Consistency of SB4 and SB2, Etanercept and Infliximab Biosimilars

“…Differences in quality attributes have been observed for marketed products [2,[6][7][8][9][10]. In limited cases, changes in quality attributes have led to clinically relevant differences between different batches of the same product [11][12]. Recently this was shown for originator version of the monoclonal antibody trastuzumab (Herceptin ® ), where a drift in the proportion of non-fucosylated glycans was associated with a reduced event-free survival (EFS) rate in patients receiving trastuzumab in the neo-adjuvant setting [12].…”

“…Specifications define the standards for ensuring consistent quality of a (biological) product throughout its lifecycle. They are agreed upon with regulatory authorities and include a large number of in-process controls and tests, as well as release criteria, so that no significant drifting of CQAs occurs over time, for example, following changes to its manufacturing process [11,[14][15][16]. By definition, a CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.…”

Influence of biosimilar infliximab launch on the utilization pattern of biological medicines: the case of Hungary

“…After patient expiry, new biosimilar medicines come to the market with price discount. Biosimilars with EMA/ FDA approval have similar safety and efficacy profile as the original biological medicines in case of new patients [20][21][22]. In an internal price referencing system, such price discount may also incentivize the manufacturer of the off-patent originator product to decrease price.…”