Analytical

Analytical Support for Biologics: A Conversation with Almac Sciences

Almac Sciences (a member of the Almac Group) recently expanded its suite of analytical solutions to include biologics testing. This follows a 2019 expansion of the company’s facility in Athlone, Ireland, where it provides a comprehensive range of flexible pharmaceutical testing services to support drug development programs adhering to industry regulations and good manufacturing practice (GMP) standards. “Biologics have gained huge traction in the past decade and are poised for stronger growth in the coming years with potential to significantly…

Ultrasonic Flow and Bubble Sensors: Optimize Process Quality in Single-Use Bioprocessing Applications

Process monitoring in laboratory and production environments enables continuous control and optimization of critical process parameters. Hence, the early detection of errors is an effective means of increasing process efficiency and reproducibility, improving quality and safety parameters, and reducing long-term costs. Highly precise and flexible noncontact clamp-on flow and bubble sensors are useful instruments to fulfill these goals. They can be applied effectively to buffer and media preparation, chromatography and filtration systems, bioreactors and fermentors, feed and transfer lines, and…

Ultracentrifugation for Recombinant Adenoassociated Virus Therapies

Quantitation of different capsid species in viral-vector gene-delivery drugs, including recombinant adenoassociated virus (AAV) therapies, is essential for proper assessment of critical quality attributes before regulatory approval and during commercial production. If rAAV full-capsid percentages are maximized, and variants such as empty or partially-filled capsids are reduced as much as possible, then potency is increased for improved dosing and tolerance outcomes. Traditionally, characterization of AAV purity with respect to empty, full, and other variants has been performed by techniques such…

Quality Risk Management for Filter Integrity Testing: Compliance with EMA’s Future Annex 1

Quality risk management (QRM) is a systematic process for assessment, control, communication, and review of risks to the quality of a pharmaceutical product across its lifecycle. Although QRM is not new (1), the regulatory focus on QRM will increase with the arrival of the European Medicines Agency’s (EMA’s) Annex 1 (2), which was reviewed by the US Food and Drug Administration (FDA), the World Health Organization (WHO), and the Pharmaceutical Inspection Convention Scheme (PIC/S). Integrity testing of sterilizing-grade filters is…

Endotoxin Questions and Answers

Endotoxin — also known as lipopolysaccharide (LPS) — is a large molecule made up of a lipid and a polysaccharide portion found in the outer membrane of each Gram-negative bacterial cell. Examination of endotoxins is necessary for microbial and animal cell-culture operations that produce active pharmaceutical ingredients (APIs) and vaccines. If a cell culture is contaminated with endotoxins, it could affect cell growth and function (thus potentially affecting product quality). Biopharmaceutical companies need to understand the endotoxin levels within their…

Ask the Expert: Mass Spectrometry for Relative and Absolute Quantitation of Process-Related Impurities

Qualitative and quantitative analyses of process-related impurities are critical to manufacturing a safe, high-quality drug product. During his 17 June 2020 “Ask the Expert” webcast, Steven Broome (BioPharmaSpec) described using mass spectrometry (MS) for such analyses. Focusing on isopropyl-β-D-thiogalactopyranoside (IPTG), kanamycin, and host-cell proteins (HCPs), Broome overviewed best practices for using MS to detect and quantitate low levels of impurities. Broome’s Presentation Chemicals used in biotherapeutic production can be present as impurities in the resulting drug product. These impurities can…

Use of CRISPR and Other Gene-Editing Tools in Cell Line Development and Engineering

While the role of biologics in treating human diseases has evolved dramatically over the past decade, so has genetic engineering. Rational genetic engineering to enhance biotherapeutic proteins has become a reality catalyzed by publication of the genome sequences of multiple Chinese hamster ovary (CHO) cell lines. Novel “designer” CHO cells modulate posttranslational modifications (PTMs) of recombinant proteins by genome editing, and it is now possible to knock-in or knock-out genes of yeast and mammalian cells precisely (within one DNA base…

Development of Patient-Focused Commercial Specifications: Understanding Clinical Relevance and Criticality of Quality Attributes

The CASSS chemistry, manufacturing, and controls (CMC) Strategy Forum on 23 January 2019 in Washington, DC, was entitled, “The Development of Patient-Focused Commercial Specifications Through Understanding of Clinical Relevance and Criticality of Quality Attributes.” This forum covered the definition, identification, control, and management of patient-focused attributes throughout the life cycle (from discovery through approval) of biological products, including vaccines. Participants investigated how to differentiate through the product development life cycle which attributes are “clinically meaningful” from those applied for manufacturing…

Breaking the Bottlenecks: Accelerating Viral Vector Bioanalysis in Downstream Processing

The rise in popularity of viral-vector–based gene therapies and SARS-CoV-2 vaccines has created a shortage of manufacturing capacity, driving efficiency improvements to avoid bottlenecks in bioanalysis to support culture optimization and bioprocessing steps. To improve workflows in bioanalytical assay development and sample analysis, more efficient methods are needed that include higher throughput, simpler and more streamlined sample assay methods, wide dynamic ranges, and efficient data processing and interpretation. Gyrolab™ microfluidic, nanoliter-scale immunoassay systems provide an innovative, robust solution to high-performance…

Peptide Therapies: Designing a Science-Led Strategic Quality Control Program

Peptide therapeutics are a unique class of pharmaceuticals. They can fall into one or more regulatory categories: as conventional chemical molecules, biological entities, or biosimilars. Developing a well–thought-out quality control (QC) strategy is key to meeting development milestones and complying with evolving regulatory requirements. Safety assessment is critical because slight changes in the structure, physicochemical properties, stability, and impurity profile of a peptide can provoke an adverse immune response. A robust analytical QC program should be conducted in laboratories that…