QA/QC

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…

eBook: Drug-Delivery Systems — 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…

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…

Certified Reference Mixtures in Extractables Screening of Polymeric Materials: For Container–Closure Systems and Single-Use Equipment

Plastics have been used for decades in container–closure systems (CCS) for drugs and in single-use (SU) manufacturing equipment for biopharmaceutical processing. Biomanufacturers must comply with national and international laws and regulations that require proof that use of such polymeric materials is safe (1, 2). That necessitates testing for potential biological responses and interactions with drug substances. Comprehensive extractables and leachables (E&L) studies also are required for potential release of undesired compounds from polymers. Extractables tests are performed on materials under…

Process Intelligence: Gene Therapy Case Study Shows That the Journey to Improved Capabilities Starts with One Step

The product development team at a gene therapy contract development and manufacturing organization (CDMO) was working on a high-priority drug-substance project for a key client. The material was crucial to that client’s early stage clinical trial, with an immediate value over US$500,000 to both the client and the CDMO. Unfortunately, the bioreactor used in the upstream process — a transfection unit operation for an adenoassociated virus (AAV) vector — had developed an intermittent problem that could force it to shut…

Smart, Real-Time Quality Insights Boost Life Sciences Manufacturing

The COVID-19 pandemic has shone a light on restrictive business processes, information silos, and poor supply-chain visibility in many sectors. In biopharmaceutical manufacturing, for example, difficulties associated with product-quality management have been exposed and starkly felt. However, public healthcare measures over the past 18 months have put physical distance between team members, thereby hampering the usual form-filling, manual sign-offs and spreadsheet-based recordkeeping associated with monitoring traditional manufacturing processes. In some cases, a lack of formal face-to-face discussions in the workplace…

Mycotoxin Risk Determination: Measuring the Potential for Patient Exposure with Antithrombin Alfa Sourced from Transgenic Goat Milk

Antithrombin alfa is a recombinant human antithrombin developed as an anticoagulant treatment for people with hereditary antithrombin deficiency who are undergoing surgical or childbirth procedures (1). Marketed under the ATryn brand name by LFB SA (Les Ulis, France), antithrombin alfa was approved for use in adults by the US Food and Drug Administration (FDA) in February 2009 (2). Antithrombin alfa is expressed in the milk of transgenic goats and purified through a multistep downstream process encompassing both filtration and chromatography.…

Supplementing Gamma Sterilization with X-Ray and E-Beam Technologies: An International Industry and Academia Collaboration

Ionizing-technology–based industries are growing rapidly around the world. The expansion is driven mostly by the technology’s myriad applications, including polymer crosslinking, medical device sterilization, food pasteurization, and phytosanitary treatment. Ionization also is used in the manufacture of some healthcare products such as medical devices and biopharmaceuticals. Industrial sterilization methods render single-use products and manufacturing components safe and ready for their intended use. ISO11137-1 describes the validation and routine control of a sterilization process for medical devices and mentions the three…