QA/QC

Outsourcing Stability Testing: Discussions with Contract Laboratories

Stability testing is required for all biopharmaceutical drug products to detect all changes in identity, purity, and potency as a result of a number of environmental and processing factors. Whether testing is conducted in-house or through contact laboratories, it involves the development and performance of comprehensive and specific stability protocols for all stages of a product’s life cycle (1). Testing product stability in-house requires signficant time and resources, and carries challenges associated with commercialization market, time, and capacity. Market: The…

Special Report on Assays, Test Methods, and Comparability The CMC Strategy Forum Series, Part 4, Biosimilar Products: Scientific Principles, Challenges, and Opportunities

The Chemistry, Manufacturing, and Controls (CMC) Strategy Forum held on 22 January 2012 in San Francisco, CA, focused on selected scientific and regulatory aspects in the development of biosimilar products. Such products are an increasingly important area of interest for both the biopharmaceutical industry and its regulatory agencies. Biosimilars are highly complex, so scientists have been unable to demonstrate identity to a level typically possible for small molecules. Consequently, specific scientific and regulatory approaches are required to ensure the high…

Special Report on Assays, Test Methods, and Comparability The CMC Strategy Forum Series, Part 4, The Role of Higher-Order Structure in Defining Biopharmaceutical Quality

Cosponsored by CASSS (an International Separation Science Society) and the US FDA, the 17th CMC Strategy Forum was designed to explore the relationships between higher-order molecular structure and quality of therapeutic proteins and peptides, vaccines, and blood-derived products. Understanding those relationships is important to defining and controlling the critical quality attributes (CQAs) of biopharmaceutical products. The forum program highlighted the current state of the art for analytical tools used to monitor higher-order structure. Case studies demonstrating the effects of changes…

Special Report on Assays, Test Methods, and Comparability The CMC Strategy Forum Series, Part 4, Demonstrating Comparability for Well-Characterized Biotechnology Products: Early Phase, Late Phase, and Postapproval

Challenges and approaches in demonstrating comparability of a well-characterized biotechnology product after manufacturing changes can be as varied and complex as the products themselves. Participants at the January 2005 CMC Strategy Forum sought to discuss and agree on common implementation strategies for different manufacturing change scenarios (1). Development of flexible, comprehensive approaches in strategy development addressed evaluation of critical product characteristics, appropriate process steps to test, numbers of lots and levels of testing required, and assessment of product comparability. The…

Special Report on Assays, Test Methods, and Comparability The CMC Strategy Forum Series, Part 4, The Roles of Bioactivity Assays in Lot Release and Stability Testing

A January 2007 CMC Strategy Forum on the roles of bioactivity assays in lot release and stability testing was held in Washington, DC (1). Its purpose was to promote an understanding of the design and utility of bioassays throughout product development and to delineate the conditions under which surrogate assays could be used to determine product potency. Topics of discussion included appropriate assay selection at each stage of product development, the potential use of binding assays for potency testing, and…

Quantitative Risk Assessment of Bioaccumulation Attributable to Extractables and Leachables in Cellular Immunotherapy Biomanufacturing

Precious patient samples, contamination concerns, and limited product purification options have compelled manufacturers of cellular immunotherapies (iTx) such as chimeric antigen receptor T cells (CAR-T) and T-cell receptor (TCR) technologies toward the disposables industry. Such companies are implementing single-use technologies (SUTs) almost exclusively (1). But despite the dominance of disposable bioprocess platforms and their extraordinary growth in the iTx marketplace, researchers have made limited efforts to understand the perennial and critical bioprocessing risks of leachables and extractables. Here we outline…

Identification and Quantification of Heat-Shock Protein 70: A Major Host-Cell Protein Contaminant from HEK Host Cells

Recombinant therapeutic proteins are commonly produced by cell lines such as Chinese hamster ovary (CHO), human embryonic kidney (HEK) 293, murine myeloma (NS0), and Escherichia coli bacterial cells. Host-cell proteins (HCPs) are indigenous proteins produced by those expression hosts and considered to be process-related impurities generated from the cell culture process (1). HCPs are potentially harmful and immunogenic to patients, and they can compromise the stability of protein drugs (2–4). For those reasons, HCPs must be consistently removed or reduced…

Comparison of Concentration Measurement Technologies in Bioprocess Solutions

Biopharmaceutical manufacturing involves complex process steps. Exacting production conditions are typically required to maximize the yield, purity, and quality of biological products. In recent years, process analytical technology (PAT) has been increasingly used to monitor key process and performance parameters in real time. That has enabled better control of production conditions. An important parameter required to achieve consistent results in many bioprocessing steps is solute concentration in process fluids. The Critical Need for Concentration Measurement Many biopharmaceutical manufacturing process steps require measuring…

Compatibility Assessment of a Model Monoclonal Antibody Formulation in Glass and Blow–Fill–Seal Plastic Vials

Blow–fill–seal (BFS) technology has been recognized by the industry as an advanced aseptic solution (1–3). Catalent Pharma Solutions has been commercially supplying sterile BFS products to the pharmaceutical industry for decades, primarily in the respiratory and topical ophthalmic markets. Such product formulations range from simple solutions to emulsions with drug substances from classical small molecules to large complex proteins such as biologics. The company also has optimized BFS processes and its Advasept plastic container system for the manufacture of sterile…

Variables in “Passive” Cryopreservative Methods: Standardizing Cell-Based Assays By Reducing Cryopreservation-Induced Variability

Cells have become essential in modern medicine as therapies, vehicles for producing high‑value therapeutics, and tools for high‑throughput screening of pharmaceutical compounds. In the latter area, more than 50% of drug discovery screens use cell‑based assays, predominantly targeting receptors and ion channels using fluorescence‑based measurements, in either or both high‑ throughput and high‑content formats (1). Alongside a cell therapy market estimated to be worth some $5.0 billion by 2015 (2), the larger cell‑ based screening market is estimated to be…