QA/QC

The Role of Medical Affairs in Moving from R&D to Commercialization

Bringing a new pharmaceutical product to market is a unique process based on a number of requirements for supporting a product launch. For a research and development (R&D) company, launching a product into market may seem to be an issue for someone else to handle in the far-distant future and at a much later time. But even at laboratory or early development stages, biotechnology companies should understand the language of pharmaceutical companies and know how that industry operates. Doing so…

Single-Use Technologies in Cell Therapy

Single-use technologies (SUTs) are tools that can be used in producing cell therapies and personalized medicines. Such products must meet specific requirements because of the way they are used. To meet those criteria, the cell therapy industry simply has no alternatives to single-use systems. SUT applications are rapidly changing. Traditional uses for single-use systems in cell therapy include processing in clinical settings (e.g., blood bags, transfer sets) and research and development (e.g., T-flasks, pipettes). Although such applications continue, the commercialization…

Automation of Cell Therapy Biomanufacturing

Biomanufacturing automation is an established mission-critical step in the commercialization pathway for conventional therapeutics, including small molecules and monoclonal antibodies (MAbs) (1). The prospect of a potential biologic progressing into late-stage clinical trials without a robust biomanufacturing strategy to support at least pilot-plant scale bioprocessing is simply unthinkable. Conversely, the cell therapy industry (or at least a significant proportion of it) regard this as a trend that is unlikely to be mirrored as the industry develops. The aim of this…

Managing Contamination Risk While Maintaining Quality in Cell-Therapy Manufacturing

With an increasing number of cell therapies becoming available for patient use, the need for controlled and consistent manufacturing and delivery of cell products is increasingly important. A closed cell culture process not only offers control and consistency, but may also relieve labor demands. Single-use components within a closed process also can reduce contamination risk. Closed systems with single-use platforms may reduce the risk of biological contamination and cross-contamination that could inadvertently be introduced into cell-culture processes. Such contaminants use…

Manufacturing Culture

Life sciences company leaders need to put the right people, processes, and technologies in place to create evolutionary cultures. Such cultures would embrace advanced manufacturing process intelligence and reap related business benefits. Since the late 1990s, my software company has helped biomanufacturers improve their process understanding. In that time, we’ve seen regulatory drivers such as quality by design (QbD) and process analytical technology (PAT) guidances call for improved manufacturing process performance through better process understanding and optimization. We define process…

Prior-Knowledge Assessments

    Process characterization (PC) studies are experiments performed primarily at laboratory scale to demonstrate process robustness and provide data necessary for planning, risk mitigation, and successful execution of process validation (1, 2). These typically involve extensive, multifactorial testing designed to determine the effects of operational parameter perturbations and raw materials on process performance and product quality (1, 2). Product-specific information from development studies may be used to help guide PC study design; however, such information may be limited or…

Integrity Testing of Ultrafiltration Systems for Biopharmaceutical Applications

    Ultrafiltration (UF) is a membrane-based separation technology commonly used in the biopharmaceutical industry for concentration or diafiltration of protein solutions to remove low–molecular-weight (LMW) impurities or exchange buffers. The nominal MW limit of UF membranes ranges from 1,000 Da (1 kDa) to 1,000,000 Da (1,000 kDa). A target product is retained by the membrane while lower-MW solutes or impurities pass through (1). For a target product with a smaller MW than the impurities, separation is accomplished by allowing…

A Decade of Characterization

    Over the past 10 years, the biopharmaceutical industry has placed increasing pressure on analytical laboratories, whose work is more important to the success of biotherapeutic products than ever before. Nearly concomitant with the appearance of BPI on the scene, the US Food and Drug Administration put forth its final report on the 21st century good manufacturing practice initiative, which in changing how regulators would review product applications, changed how companies must approach them (1). The guiding principles —…

Balancing the Statistical Tightrope

During one development meeting early in my industrial career, a process development group member asked me whether the value my group had reported in one result was okay to use. I confidently replied “Yes, it’s fine. It’s about 40, somewhere between 38 and 42. The other person raised his eyebrows. “About 40?” In response, I somewhat awkwardly mumbled “Yes, probably…about that” — an answer not met with full understanding, but rather concern. My answer hadn’t been incorrect. The result was…

An Industry Perspective on Quality By Design

The US FDA’s quality by design (QbD) initiative and associated ICH Q8, Q9, and Q10 guidance documents are increasingly embraced by the biopharmaceutical manufacturing industry for ensuring consistent product quality and lower costs of development and manufacturing. One critical problem the industry faces involves understanding how to implement QbD and determine the benefit of such projects — which require the work of many groups across quality, manufacturing sciences, and engineering departments. Here we present the results from a survey of…