Analytical

Development of a Host-Cell Protein Platform Assay for a Chinese Hamster Ovary Cell Line

The Chinese hamster ovary (CHO) cell line is the most prevalent biopharmaceutical expression system and has been proven safe for commercial production of protein therapeutics (1). However, even after multiple purification steps, biopharmaceuticals contain residual host-cell protein (HCP) impurities that pose a potential safety risk to patients (2). Health authorities demand close monitoring of HCP impurities and require sensitive analytical methods with high coverage: the ability to detect a broad range of HCP impurities (3, 4). Polyclonal sandwich immunoassays are…

Moving DSC Downstream: Exploiting Differential Scanning Calorimetry As a Process Development Tool

The primary goal of biopharmaceutical process development is to determine what steps and conditions will maximize and optimize yields of purified product in the most reproducible, robust, and cost-efficient way. Characterized by high batch-to-batch comparability minimizing economic losses associated with batch failures, success relies on a thorough understanding of a given biological drug. Determining how its activity and stability are affected by processing and how to mitigate and control associated risks is advocated by a quality by design (QbD) approach.…

Development Approaches to Adenoassociated Virus Production

After many years of development, gene therapy is beginning to deliver on its promises in the clinic, in some cases with spectacular outputs. Those clinical successes also have led to an influx of funding and engagement from large pharmaceutical companies, thereby bringing the required financial support and expertise for late-stage clinical developments and product commercialization. Although many initial studies were confined to small patient groups and focused on a range of rare monogenetic diseases, new approaches to gene editing have…

BPI Lab: Essential Technologies for Development, Characterization, and QA/QC

There’s a secret hiding in plain sight: many analytical methods and technologies initially designed for pre-clinical development have equally important applications in commercial development. BioProcess International and BioTechniques, sister publications and leading journals that combined, cover the entire biopharmaceutical process, from discovery to development and manufacturing, partnered to create this special eBook, highlighting and detailing fourteen analytical technologies that provide laboratory technicians and scientists with vital information to help project managers and engineers make educated decisions that ultimately affect every…

Opportunities and Challenges in Biosimilar Development

A biosimilar biotherapeutic product is similar (but not identical) in terms of quality, safety, and efficacy to an already licensed reference product. Unlike generic small molecules, it is difficult to standardize such inherently complex products based on complicated manufacturing processes. Table 1 describes the main differences between biosimilar and generic drug molecules. The global biosimilar market is growing rapidly as patents on blockbuster biologic drugs expire (Table 2) and other healthcare sectors focus on reduction of costs. Biologics are among…

Implementing Quality By Design in Analytical Development: A Case Study on the Development of an Anion-Exchange HPLC Method

The concept of quality by design (QbD) initially was outlined in ICH Q8 guidance for drug-product development and later in Q11 for drug-substance development (1, 2). Since then, the QbD concept was further expanded to the development of analytical methods. FDA issued a 2015 guidance on analytical procedures and method validation for drugs and biologics (3). Although the agency did not explicitly state the requirement for implementation of QbD in analytical method development, the concept is embedded in its section…

Special Report: Effect of Insulin on Cell Growth and Virus Production

Recombinant insulin is a key component in serum-free growth media for mammalian cells. It is used for the manufacturing of monoclonal antibodies, virus vaccines, gene therapy products and many other biological drug products approved by regulatory bodies worldwide, including FDA and EMA. Canada’s National Research Council (NRC) helps companies develop and commercialize new health technologies. Recently it partnered with Novo Nordisk Pharmatech to determine the effect of Insulin on cell growth and virus production. The results are detailed in this…

Advancements in Characterizing Therapeutic Protein Higher-Order Structure

Electrospray-ionization mass spectrometry (ESI-MS) is a well-established tool for biotherapeutic analysis. It draws intact proteins or peptide ions into the vacuum of a mass spectrometer, where the ion mass is measured. Electrospray ion-mobility mass spectrometry (ESI-IMS) introduces ions into a low-pressure gas, where the effects of aerodynamic drag reveal their shape. This technique is just emerging as a valuable tool for characterizing intact proteins, even though for a decade it’s been the basis of a commercially available medical diagnostic test…

Aggregation from Shear Stress and Surface Interaction: Molecule-Specific or Universal Phenomenon?

Exposure to solid–liquid and air–water interfaces during production, freezing and thawing, shipment and storage of protein therapeutics may be a contributing factor in their degradation (e.g., aggregation, fragmentation) (1, 2). Surface exposure, particularly during manufacturing processes, often is accompanied by various degrees and durations of shear stresses originating from fluid flow and acting on proteins at interfaces. The magnitude and duration of shear rates depends on velocity gradients within each solution and varies significantly among manufacturing steps. On the low…

Strategies for Successful Sample Transfer

Nadine Ritter is president and senior analytical advisor of Global Biotech Experts, LLC and a long-time member of BioProcess International’s editorial advisory board. At a recent CASSS North American CMC Strategy Forum called “Methods on the Move: Addressing Method Transfer Challenges,” she discussed the biopharmaceutical industry’s logistical challenges of analytical test samples for drug substances and products. At the conference, BPI’s editor in chief Anne Montgomery met with her to discuss some key points of this topic. Logistics Challenges Montgomery:…