QA/QC

Prepacked Chromatography Columns: Evaluation for Use in Pilot and Large-Scale Bioprocessing

Time to market, resource requirements, cost, and flexibility are key considerations in designing purification processes suitable for manufacturing biopharmaceutical products. Over the past decade, many advances have been achieved in disposable processing systems that have allowed for increased processing at a lower cost. That is in part attributable to reductions in necessary resources, changeover costs, and cleaning-validation requirements. Large-scale, prepacked chromatography columns have recently become available for clinical and commercial manufacturing, and they represent a growing trend in the industry.…

Benefits of Using Tetradetector SEC to Characterize Membrane Proteins

About 60% of all drug targets are membrane proteins. So understanding their structure and function as well as their interactions with drug candidates is critical to discovery and development of new therapeutic agents. Solubilization of these proteins is an essential precursor to in vitro studies of receptor function, structure, and activity. Purification and crystallization are important aspects. However, solubilization is complicated by the hydrophobic nature of a protein’s membrane-spanning part. Surfactant micelles and other stabilizing systems thus are used to…

Virus-Filtration Process Development Optimization: The Key to a More Efficient and Cost-Effective Step

Size-exclusion–based parvovirus filtration is an important step toward drug product safety in biopharmaceutical production. However, once a virus filter is in place, and the required virus safety is ensured, less attention typically is paid to its optimization within the process. That might seem odd given that virus filtration can be one of the more expensive downstream processing steps ($/g protein processed). Most likely, the lack of attention can be attributed to aggressive timelines, limited process development resources, and the virus…

Detecting the Broad Spectrum of Pyrogens with the Human Whole-Blood Monocyte Activation Test

In the early 20th century, some patients injected with the drug Salvarsan experienced febrile reactions due to contamination of the drug’s distilled water. That incident (involving the first effective treatment for syphilis) prompted not only the widespread use of injectable drugs, but also the need for pyrogen control. Pyrogens constitute a heterogeneous group of microbial and nonmicrobial substances that include those derived from Gram-negative and Gram-positive bacteria such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively, as well as particles…

Defining Your Product Profile and Maintaining Control Over It | A Look Back with Emily Shacter

This is a transcript from a Q&A interview with Emily Shacter, PhD, Consultant, ThinkFDA LLC (former FDA Scientist and Regulator). We will be talking today about the CMC Forum that was published back in 2005. We are revisiting it in the magazine to specifically update our understanding of how to maintain process control; understanding your process. In general, how do you feel the discussions in the four-part paper from 2005 has held up after 10 years? Emily: I think they…

Bridging Analytical Methods for Release and Stability Testing: Technical, Quality and Regulatory Considerations

To monitor the control and consistency of products derived from biological systems, a broad array of analytical methods are used for biopharmaceutical release and stability testing. These methods include both classical and state-of-the-art technologies as well as new technologies as they emerge over time.During the life cycle of a product, several reasons can arise for making changes in existing analytical methods: e.g., improved sensitivity, specificity, or accuracy; increased operational robustness; streamlined workflows; shortened testing times; and lowered cost of testing.…

Process- and Product-Relate Impurities: Part 1 – Process-Related Impurities An Overview

Introduction by Cheryl Scott The CMC Strategy Forums focus on relevant chemistry, manufacturing, and controls (CMC) issues throughout the life cycle of a therapeutic and thereby foster collaborative technical and regulatory interaction. Forum chairs share information with regulatory agencies to help them merge good scientific and regulatory practices. Outcomes of forum meetings are published in BioProcess International and on the CASSS website (www.casss.org). This process is meant to help ensure that biopharmaceutical products manufactured with advancing technologies in a regulated…

High-Throughput Methods Evaluation: Impurities Determination During Upstream and Downstream In-Process Development

Getting biologic drugs through development and into clinical proof-of-concept studies quickly and efficiently is critical for success in the biopharmaceutical industry. Implementing high-throughput approaches to both upstream and downstream process development is increasingly helping companies stay competitive. Innovative and highthroughput analytical technologies are needed to support rapid process development. The study reported herein focuses on innovative immunoassay platforms for impurity-removal monitoring of both host-cell proteins (HCPs) and leached protein A. HCPs come from host cells during cell culture production. Their…

Using Glycosidases to Remove, Trim, or Modify Glycans on Therapeutic Proteins

One of the most common posttranslational modifications of eukaryotic proteins is glycosylation. Glycosylation of proteins can affect many biological activities. For therapeutic glycoproteins, it can modify biological activity, targeting, trafficking, serum half life, clearance, and recognition by receptors (1, 2). For such reasons, biomanufacturers must monitor and characterize the glycosylation patterns of their recombinant therapeutic proteins (3, 4). Therapeutic proteins have two main types of glycosylation: N-linked glycans and O-linked glycans (5). Attachment of an N-glycan starts in the endoplasmic…

Development of a Novel Host-Cell Protein Assay: Supporting the Physcomitrella patens Expression System

Host-cell proteins (HCPs) constitute an inevitable impurity of biopharmaceutical products originating from recombinant-cell culture. HCPs are a heterogeneous mix of different proteins, their specific characteristics depending on the kind of organism used as an expression platform, on the “destination” of the expressed recombinant product (extra- or intracellular), and on the corresponding purification approach (1–3). Contamination of a final drug substance with residual HCPs could lead to immunogenic reactions in some patients who receive the drug product (DP). So a reliable…