Risk Management

Polysorbates, Biotherapeutics, and Anaphylaxis: A Review

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Rapidly increasing use of monoclonal antibodies (MAbs) in the treatment of neoplastic, autoimmune, and inflammatory diseases has led to a dramatic increase in hypersensitivity reactions worldwide, complicating the use of MAbs as first-line therapies and limiting patient survival and quality of life (1). The origins of anaphylaxis are not well understood, though its mechanism is fairly straightforward (Figure 1). It is usually attributed to some undefined intrinsic property or properties of a biotherapeutic — despite the fact that biotherapeutic formulations…

September 19, 2017

Response to the Publication of USP ‹1207›

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The BioPhorum Operation Group’s (BPOG’s) Container Closure Integrity Testing (CCIT) workstream would like to congratulate the United States Pharmacopeia’s committee for its latest revision to USP chapter <1207> Package Integrity Evaluation: Sterile Products. Generally, we believe it provides a comprehensive overview of the available methods for container–closure testing and outlines many important elements for consideration in establishing a successful CCIT strategy. We first responded to the USP <1207> draft when it was released for comment in 2014. And from our…

January 19, 2017

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

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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…

October 17, 2016

Viral Risk Evaluation of Raw Materials Used in Biopharmaceutical Production

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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…

October 14, 2016

Achieving Competitive Advantage in the Biopharmaceutical Industry

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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…

April 12, 2016

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

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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…

February 4, 2016

Disposable Components in Biomanufacturing: A Regulatory Perspective

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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…

December 18, 2015

A Risk-Based Approach to Supplier and Raw Materials Management

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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…

November 17, 2015

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

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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,…

November 17, 2015

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

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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…

November 17, 2015