Risk Management

Figure 2: Starting material for modified T-cell production

Manufacturing Plasmid DNA: Ensuring Adequate Supplies for Gene and Cell Therapies

The concept of gene therapy is far from new, with initial studies performed over 20 years ago (1). However, in the past few years an explosion of interest in this area has gone beyond initial regenerative approaches using viral vectors. Interest is now moving increasingly into potential use of T cells modified using recombinant viral vectors for immunotherapy applications. Such therapies are based on using either adenoassociated virus (AAV) or lentivirus (1), both vectors being frequently generated through transient expression…

Figure 1:  Raw materials high-level classification

Viral Risk Evaluation of Raw Materials Used in Biopharmaceutical Production

Ensuring a continuous supply of safe medicines to patients is a key objective for both health authorities and the pharmaceutical industry. A critical component to that end is maintaining a reliable supply of qualified raw materials (RMs). Manufacturers must ensure not only the suitability of RMs for their intended use in a manufacturing process, but also their highest attainable safety with regards to viruses and other adventitious agents. The need to apply a risk-based RM control strategy is in line…

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Achieving Competitive Advantage in the Biopharmaceutical Industry

Drug development is a complex process that is associated with high drug-candidate attrition rates, long development times, and high costs (1, 2). Drug development costs have increased over the past two decades, with current average development cost of about US$2.6 billion, of which $1.4 billion is the direct cost (1, 2). On average, drug development takes at least 10 years to market authorization (2). Biopharmaceutical companies often follow a strategy of developing drugs for multiple clinical indications and biological targets…

Figure 1: (a) Two-dimensional (2D) sodium-dodecyl sulfate polyacrylamide gel electrophoresis (SDSPAGE) total protein Coomassie stain of the Physcomitrella patens HCP antigen mix, 600 µg protein per gel; (b) 2D SDS-PAGE total protein silver stain of the P. patens HCP antigen mix, 300 µg protein per gel; (c) quality control testing of the total antiserum pool by 2D Western blot, 300 µg protein per gel;  (d) quality control testing of the capture antibody by 2D Western blot, 300 µg protein per gel

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…

Filter cartridges like these are commonly used in facilities that are primarily stainless steel as well as those based on single-use technologies. PALL LIFE SCIENCES (WWW.PALL.COM)

Disposable Components in Biomanufacturing: A Regulatory Perspective

On a holistic level, the decision regarding whether to use single-use or stainless steel equipment in a biomanufacturing plant is a significant one. It greatly influences the design, construction, layout, and operation of a plant — and consequently, the timing and cost of the overall project. And regulatory review can add an element of risk to using anything new. Disposables have been viewed as a revolutionary concept, and they are. But from a routine regulatory operational perspective, I believe it…

13-10-Shimoni-F2

A Risk-Based Approach to Supplier and Raw Materials Management

Ensuring a continuous supply of safe medicines is a key objective for the pharmaceutical industry and health authorities alike. A critical component to that end is maintaining a reliable supply of qualified raw materials (RMs) used in drug production. However, changes in suppliers, their processes, their providers, and consequently the materials they supply can occur (for a number of reasons) at any time during the life cycle of drug production. A product-supply organization therefore must be prepared to address such…

Photo 1:  A single-use quaternary pump chamber (Quattroflow) coupled with genderless connectors (AseptiQuik, CPC) for sterilemanufacturing systems

Next-Generation Bioprocessing for Meeting Healthcare Challenges: The Role Single-Use Handling Systems Can Play

The rapid spread of contagious and lethal diseases worldwide has driven bioprocess suppliers to develop technologies for use in producing disease treatments and vaccines. Bioprocessors need to develop new biologics as well as rapid and reliable methods for bringing those treatments to commercialization. Implementing modular process solutions and single‑use handling systems in closed‑manufacturing processing is one approach to addressing those needs. Developing and discovering solutions for meeting global healthcare conditions is an evolving part of bioindustry. As points of reference,…

Special Report on Assays, Test Methods, and Comparability The CMC Strategy Forum Series, Part 4, The Role of Higher-Order Structure in Defining Biopharmaceutical Quality

Cosponsored by CASSS (an International Separation Science Society) and the US FDA, the 17th CMC Strategy Forum was designed to explore the relationships between higher-order molecular structure and quality of therapeutic proteins and peptides, vaccines, and blood-derived products. Understanding those relationships is important to defining and controlling the critical quality attributes (CQAs) of biopharmaceutical products. The forum program highlighted the current state of the art for analytical tools used to monitor higher-order structure. Case studies demonstrating the effects of changes…

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Management, Notification, and Documentation of Single-Use Systems Change Orders: Challenges and Opportunities

Single-use systems (SUS) consist of numerous plastic components derived from different suppliers. As such, they are prone to changes, including alterations in construction materials or modifications in manufacturing processes. Such changes may originate at the immediate supplier or farther back in the supply chain as a result of product improvements, process improvements, part discontinuation, or even business decisions such as manufacturing site relocation. Whether those changes are major or minor, managing their impact on biopharmaceutial processes and product quality often…

Manufacturing Strategies: BPI Theater @ Interphex 2015

Bill Hartzel (director of strategic execution for advanced delivery technologies, Catalent Pharma) 1:30–1:55 pm Reducing the Risk Associated with the Filling of Biologics with Advanced Aseptic Processing  Hartzel discussed leveraging “blow–fill–seal” (BFS) aseptic processing technology to reduce risks associated with biologics fill and finish. A number of drug recalls have been associated with microbial and particulate contamination of glass vials, problems that could be solved using BFS. Automation eliminates human intervention at this critical stage, driving out associated risks. Hartzel…