Risk Management

Host-Cell Protein Risk Management and Control During Bioprocess Development: A Consolidated Biotech Industry Review, Part 2

Even with increased understanding of host cell proteins (HCPs) and their potential risks, no practical approach has been made available for HCP risk management during bioprocess development. A BioPhorum Development Group (BPDG) team has identified common HCP-related risk factors and built a template for semiquantitative risk assessment during process development based on publicly available information. To this end, the BPDG HCP working team’s assay and knowledge-sharing experts have established a common HCP risk assessment tool and mitigation strategy to guide…

Host-Cell Protein Risk Management and Control During Bioprocess Development: A Consolidated Biotech Industry Review, Part 1

Host-cell proteins (HCPs) constitute a significant class of process-related impurities during biologics manufacturing. Due to their potential impact on product quality and efficacy as well as patient safety, the total amount of residual HCP in a biological drug substance generally is considered a critical quality attribute (CQA) that usually needs to be tested for during batch release (1, 2). It is both an “industrywide” common understanding and a regulatory requirement to remove HCPs from biologics to acceptably low levels that…

Back to Basics for Biotech: Driving a Culture of Quality and Compliance with Practical Communication Techniques

The robust regulatory environment surrounding biotechnology and bioprocessing demands a comprehensive current good manufacturing practice (CGMP) culture of quality, compliance, and absolute adherence to policy. Employees need to be engaged in their work, with a laser focus on meeting stringent specifications and operating under tight controls. A misstep in quality or compliance can lead to hefty fines, legal concerns, regulatory retaliation, and reputational damage. Communication and stakeholder engagement are critical to aligning organizations and driving the right culture in highly…

Beyond Compliance: Serialization Has More to Offer

As the global pharmaceutical industry implements serialization (track and trace from manufacturing to dispensing) to meet governmental regulatory requirements, other opportunities arise for drug companies. The main driver here is to improve the integrity of the overall drug supply chain, but other meaningful business benefits can come from serialization. Generally accomplished through automated, electronic means, it involves such practices as recording, authenticating, maintaining, and sharing accurate records of products. Outside-the-Box Benefits In addition to tightening up the supply chain and…

Transforming Deviation Management

All biopharmaceutical companies espouse a belief in scientific, risk-based approaches. However, with respect to deviation management systems (DMSs), the industry is falling short of that promise. By and large, companies still use a small-molecule pharmaceutical compliance model that dates back to the 1980s, based on the strategy that all deviations are created equal and require 30-day closure. Most bioprocessors still hold to a default 30-day rule, even though there is no specific regulatory requirement for that time frame. Major or…

Polysorbates, Biotherapeutics, and Anaphylaxis: A Review

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…

Response to the Publication of USP ‹1207›

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…

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…

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…

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…