QA/QC

Practical Considerations for Statistical Analyses in Continued Process Verification

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Several statistical techniques can be used to assist in monitoring biopharmaceutical product quality attributes as part of continued process verification (CPV) activities. These include run charts, control charts, and capability analyses. Below, I provide an overview and recommendations on statistical strategies when developing a CPV program, considering the expected behavior of manufacturing results in the biopharmaceutical industry. Presence of Autocorrelated Data In a previous study, I highlighted the tendency for data to be positively autocorrelated (values are closely related to…

December 17, 2020

Analytical Support for Biologics: A Conversation with Almac Sciences

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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…

December 17, 2020

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

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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…

October 29, 2020

Endotoxin Questions and Answers

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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…

October 29, 2020

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

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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…

September 22, 2020

Breaking the Bottlenecks: Accelerating Viral Vector Bioanalysis in Downstream Processing

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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…

September 11, 2020

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

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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…

September 2, 2020

Early Stage Analytical Considerations for Late Stage Biologics Success

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This BPI Special Report will cover phase appropriate analytical strategies that will balance various drivers to meet overall development goals without sacrificing the requirements of a program. The goal is to provide important recommendations for analytical method development that can help the biopharmaceutical industry identify opportunities to improve lead time and reduce development costs while maintaining required quality standards. Fill out the form below to learn more about analytical method development now.   Arugadoss Devakumar, PhD, is director of analytical…

June 26, 2020

Ask the Expert: Improving Host-Cell Protein Detection By Enriching Mass Spectrometry Samples

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Enzyme-linked immunosorbent assays (ELISAs) remain the industry standard for process monitoring and lot-release testing for host-cell proteins (HCPs), but researchers need orthogonal tests to confirm that an ELISA is fit for purpose. On 22 April 2020, Eric Bishop (vice president of research and development at Cygnus Technologies) delivered an “Ask the Expert†presentation about his company’s solution: mass spectrometry (MS) preceded by a novel Antibody Affinity Extraction (AAE) technique. Bishop explained that an AAE step can magnify a sample’s HCP…

June 10, 2020

Are You Missing the Bigger Picture with Your AAV Analytics? Fast, Low-Volume Subvisible Particle Analysis for Characterizing Viral Vectors

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Subvisible particle (SVP) analysis is a key indicator of stability and safety and is an essential parenteral drug quality metric. Yet assessment of SVPs is especially challenging in adenoassociated virus (AAV) vector formulations, in which limited precious sample is available. Traditional SVP methods consume large sample volumes, while dynamic light scattering (DLS), size-exclusion chromatography (SEC), and visual inspection can miss aggregates in the subvisible range entirely. This special report introduces backgrounded membrane imaging (BMI) technology as a solution for detection…

May 4, 2020