QA/QC Archives - Page 7 of 19 - BioProcess InternationalBioProcess International

A Novel 3D Culture System for High-Throughput Hepatoxicity Screening

by Timothy P. Spicer, Virneliz Fernández Vega, Louis Scampavia, Lynsey Willetts and Michelle Vessels

Cells grown as three-dimensional (3D) spheroids are thought to more closely mimic in vivo physiology in terms of morphology, structural complexity, and phenotype. Being more physiologically relevant, 3D cultures can be highly predictive for compound profiling and evaluating cytotoxicity, a critical step in evaluating chemotherapeutic drug candidates. Unfortunately, evaluation of drug cytotoxicity traditionally has relied on the use of two-dimensional (2D) cell culture monolayers. When grown in monolayers, cells are not exposed to soluble gradients, are forced into an apical-basal…

Certain Approaches to Understanding Sources of Bioassay Variability

by Keith M. Bower

During lifecycle development of a biological assay (bioassay), identifying and reducing sources of variability might be required to improve method performance. Here I recommend some statistical and graphical approaches (consistent with USP <1033>) for practitioners to identify variation from experimental results (1). Sources of Variation in a Bioassay To correctly identify sources of variation in a bioassay, analysts must consider how that bioassay is to be executed. In particular, the experience and technical expertise of each analyst expected to execute…

Trends in Chemistry, Manufacturing, and Controls: Next-Generation Technologies and Product Modalities

by Cheryl Scott

New technologies bring new regulatory challenges. The biopharmaceutical industry must be cautious in its implementation of new scientific ideas and technology platforms — no matter how promising those might be. Regulators will look skeptically on any claim that isn’t backed up by good data, and with no solid history of successful use to build on, a company must have all the answers itself. How do compliance professionals anticipate what kinds of questions reviewers will ask when the time comes —…

Dye Ingress Methods for Container–Closure Integrity Testing: An Industry Position Paper

by Scott Ewan, Stefanie Adler, Nicolas Coopmans, Marta Corcoran, Sean Fadden, Chris Feeney, Jason Fernandez, Henri Hebting, Olivia Henderson, Steve Klohr, Michael Koby, Josh Lance, Brian Lee, Lei Li, Doug McNeill, Roman Mathaes, Dale Moore, Jeff One, Kashyap Panya, Suzanne Pellinen, Amanda Scruggs, Kamran Simani, Mauro di Stefano, Jared Trefethan, Harold van Deinse, Brian Vanness, Amy Wang and Klaus Wuchner

The primary goal of container–closure integrity (CCI) is to maintain the sterility and product quality of parenteral biopharmaceuticals throughout their shelf life and use. Guidelines detailing the initial CCI qualification and validation requirements have been defined and can be found in the US Pharmacopeia chapter 1207 (USP<1207>) (1). The guidelines described in USP<1207> can be applied to any common CCI testing (CCIT) method to achieve a method suited for its intended use within a drug product lifecycle. CCI is not…

Setting Up a Rapid Mycoplasma Assay to Support Recombinant Protein Production

by Kent Persson

Octapharma AB (OAB) in Stockholm, Sweden, is the site for Nuwiq human recombinant factor VIII (FVIII), production. The drug is produced in a human cell line cultured in a perfusion bioreactor using a closed system (to minimize contamination) and proprietary serum-free medium without animal-derived components. In accordance with regulatory guidelines, cell banks and cell cultures used for production of biological products must be free of mycoplasma. Traditional mycoplasma testing is a growth-based method that represents a significant bottleneck in quality…

eBook: Quality By Design for Monoclonal Antibodies — Establishing the Foundations for Process Development, Design Space, and Process Control Strategies

by Brendan Cooney, Susan Dana Jones and Howard L. Levine

The quality by design (QbD) modernized approach to pharmaceutical development is intended to provide regulatory flexibility, increased development and manufacturing efficiency, and greater room to innovate as well as improve manufacturing processes within defined ranges without obtaining regulatory approval first. QbD is a systematic developmental approach that starts with a clear goal in mind and emphasizes understanding of how variability in both process and materials affects a final product (1). Historically, product quality has been assured either with end-product testing…

Methods on the Move: Addressing Method Transfer Challenges for the Biopharmaceutical Industry

by Mary Beth Pelletier, Jeffrey Staecker and Kathy Lee

Analytical method transfers are essential components of the current global biotechnology environment. Analytical method transfer can be defined as “a documented process that qualifies a laboratory (the receiving laboratory) to use a validated analytical test procedure that originated in another laboratory (sending laboratory), thus ensuring that the receiving laboratory has the procedural knowledge and ability to perform the transferred analytical procedure as intended” (1). The goal is to ensure that a method continues to perform in the validated state regardless…

Statistical Assessments of Bioassay Validation Acceptance Criteria

by Keith M. Bower

Analytical linearity as well as assessments of precision and accuracy determine the range for a bioassay (1). USP <1033> recommends comparing confidence intervals (CIs) against target validation acceptance criteria in a bioassay validation exercise, but there are no clear guidelines for determining the criteria (2). Here I address several aspects of a bioassay validation, namely • Linearity (coefficient of determination (R2), slope, and intercept parameters) • Accuracy (%relative bias, %RB) • Precision (percent coefficient of variation, %CV) CIs for the…

Ensuring the Integrity of Single-Use Containers: Providing Robustness, Science, and Helium-Based Technology with a Detection Limit of 2 μm

by Marc Hogreve, Carole Langlois, Marie-Christine Menier and Saeedeh Aliaskarisohi

Identifying the greatest defect size, both for liquid leaks and microbial ingress, is a fundamental step toward protecting the integrity of single-use systems (SUS) under real process conditions. Integrity testing of such systems may become a prerequisite in the future because they are used in the most critical process steps, with detection limits correlating to liquid leaks and microbial ingress. Such testing guarantees the sterility of drug substances and drug products packaged in single-use systems and, therefore, enhance patient safety.…

Antibody Higher Order Structure Stability: Polymorphism Revealed By Protein Conformational Array

by Xing Wang, Lavanya Kolluru, Aarti Madhu and Michael Davies

For protein therapeutics and other biologics, the importance of the molecule’s structure to its efficacy and safety is well established (1–5). In particular, their tertiary and quaternary structures play very important roles in product quality and have been monitored extensively in comparability studies (6–12). However, because of both the large molecular size and rotational property of amino acid α carbons, a protein can assume an enormous number of different conformations (13). For antibody-based biologics such as monoclonal antibodies (MAbs), fusion…