QA/QC

The State of Quality Risk Management in the Pharmaceutical Industry: Commentary on the Draft ICH Q9 Revision

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) released a long-awaited draft revision of its Q9 guidance on quality risk management (QRM) for public consultation in December 2021 (1). First published in 2005, ICH Q9 has been instrumental in highlighting the importance of QRM in both the small- and large-molecule pharmaceutical industries. It was the first comprehensive guidance to explain how QRM could be used to identify, assess, and control risks to drug-product quality…

Container Materials for Biopharmaceuticals: A Comparative Small-Scale Case Study of Stainless Steel and a Proprietary Nickel-Based Alloy

Evaluating compatibility of a drug substance with all surfaces that it might come into contact with during drug product manufacturing is essential to ensure product quality. Proteins can adsorb to contact surfaces, form aggregates, and desorb into a drug-substance solution. Proteins also can degrade in presence of leachables generated from contact surfaces during manufacturing. Containers and vessels used during manufacturing are single-use disposable components or metal tanks, primarily either 316L stainless steel (SS) or C-276 Hastelloy nickel-based alloy (HLY). Researchers…

Opportunities in the Field of Host Cell Proteins Part 3: Case Studies in Impurity Detection and Identification

Rigorous physicochemical and bioanalytical methods must be performed on biological products to ensure that they contain minimal levels of host cell proteins (HCPs) and other process-related impurities. In the first and second parts of our article, we surveyed literature about HCPs of concern, the mechanisms behind their immunogenicity, and ultimately, their consequences for patient safety. Herein, we highlight published case studies to explore difficulties with detecting, identifying, and quantifying such impurities. These examples demonstrate that much remains to be learned…

Deciphering Nutritional Needs in Bioprocess Optimization: Targeted and Untargeted Metabolomics with Genome-Scale Modeling

Microbiology has risen as a major part of global industry over the past three decades. Industrial microbiology, biotechnology, biopharma and now biointelligent production systems (1) embrace a wide range of manufacturing platforms and product areas involving microbes, animal cells, and plant cells — as well as whole organisms. The multibillion-dollar applications of biomanufacturing display great variety. They include microbial-based production of such valuable metabolites as amino acids, vitamins, solvents, and organic acids as well as larger products such as enzymes,…

eBook: BPI Lab — Contemporary Approaches to Data and Organization

Laboratories provide essential support functions in biopharmaceutical development: from cell-line development through process validation, environmental monitoring, and preclinical analyses . . . to product characterization, formulation, and stability testing. Regulatory compliance is important across the gamut of such laboratory work. Modern companies are implementing lean concepts that facilitate organization and workflows in laboratory operations. And companies around the world can use the latest technology to ensure data integrity for their analytical results. Included herein are two articles that originally appeared…

eBook: Drug-Delivery Devices — Measurement-System Analysis Using Gauge R&R Studies

When a biological product requires a specialized delivery device, the resulting combination product can introduce new types of quality evaluation. Product development brings together regulatory requirements for biologics and drug-delivery systems, and for many people on the biopharmaceutical side, that includes a number of unfamiliar terms, processes, and procedures. Among those are gauge repeatability and reproducibility studies for measuring variations that arise from measurement devices and the operators using them. This eBook introduces the concept of attribute-data gauge repeatability and…

Opportunities in the Field of Host-Cell Proteins Part 1: Their Sources and Implications for Protein-Drug Efficacy

Biopharmaceuticals are produced in genetically modified cells; thus, they contain process-and product-related impurities. Those deriving from manufacturing processes include host cell DNA/RNA, viral DNA/RNA, cellular debris, lipids, and host-cell proteins (HCPs) (1). Mammalian, bacterial, fungal, insect, and plant cell lines have been used to overexpress recombinant proteins. Currently, the most frequently used hosts for biomolecule synthesis are Escherichia coli and Chinese hamster ovary (CHO) cells. E. coli has been used to produce heterologous proteins since the beginning of the biotechnology…

Bringing Gene-Therapy Product Quality Into Focus

Regulatory agencies are scrutinizing gene-therapy product quality more closely than ever, yet such therapies still are produced in small batches and at high costs. Thus, drug companies are struggling to make safe and efficacious gene therapies available to patients. In an April 2022 presentation, Tim Kelly (chief executive officer of Oxford Biomedica Solutions, OXB Solutions) emphasized the importance of addressing both process output and product quality when manufacturing adenoassociated virus (AAV)-based gene therapies. Such an approach requires deep expertise and…

Overcome Costly Hit-Finding Challenges Using an Integrated Platform

Thomas Meins, global head of protein production, HitS Unit, WuXi AppTec. Meins reflected that WuXi AppTec established the HitS Unit 15 years ago to facilitate drug discovery for protein biologics. Today, the unit provides a rapid and cost-effective platform for protein generation, screening, biophysical and biochemical analysis, structural determination, and “hit” confirmation. As of July 2022, the unit has produced assays for more than 1,500 recombinant proteins, including multisubunit complexes, DNA- and RNA-modifying proteins, and membrane proteins. Around 1,200 have…

Pressure Vessels for Biomanufacturing: Basic Considerations for Cleaning and Process Compatibility

Pressure vessels are enclosed containers used to contain liquids, vapors, and gases at pressures that are significantly higher or lower than the ambient pressure of their surroundings. Equipment such as bioreactors, holding tanks, mixing tanks, separators, and heat exchangers all are examples of pressure vessels. As such, they form an integral part of biopharmaceutical manufacturing. Apart from pressure containment itself, a key challenge in building pressure vessels is making them meet the high purity and cleanability requirements of bioprocessing. As…