Manufacturing

Pseudomonas fluorescens: Cell-Line Development of a Commercially Proven Platform for Biopharmaceutical Manufacturing

A number of factors contribute to delivering a robust, highly productive, and reliable process for manufacturing a therapeutic protein. They begin with a cell-host system and a gene-expression strategy that determine a developer’s ability to optimize growth and expression titers. But for many therapeutic proteins, initial attempts to develop a production process are based on evaluation of limited factors and tend to yield only small quantities or poor product quality. Automation can enable parallel building and expression screening of diverse…

eBook: Biopharmaceutical Outsourcing — Capacities, Companies, and Current Trends

Although many biopharmaceutical companies leverage in-house capabilities to produce their therapies, contract manufacturing partners represent a significant part of the biologics industry. Recent capacity investments, facility expansions, and mergers and acquisitions (M&A) activity even suggest that third-party biologics production is gaining traction. In this eBook, BioProcess Insider’s founding editor, Dan Stanton, takes the pulse of today’s outsourcing sector. First, he speaks with Dawn Ecker (director of bioTRAK database services at BDO) to establish what kinds of companies are amassing mammalian…

Managing Host-Cell Proteins: Robust Risk-Assessment Frameworks for Process-Related Impurities in Biological Products

Although biomanufacturing processes are designed to generate highly pure drug substances, some host-cell proteins (HCPs) copurify with target proteins and thus remain in finished drug products. Biopharmaceutical developers are keenly aware that such impurities must be minimized to protect patients. HCPs can activate several kinds of immune responses in treated patients, including production of antidrug antibodies and induction of cross-reactivity with therapeutic proteins (1–5). HCPs also can diminish drug efficacy, potency, and/or stability (6, 7). Thus, regulatory guidances such as…

Growing Value of Artificial Intelligence in Biopharmaceutical Operations

Some people have found significant disillusionment regarding artificial intelligence’s (AI’s) limitations in application. For example, mass-media productions (e.g., Ex Machina) encourage the goal of achieving general AI or super AI, which supplies comprehensive, self-instituted results. In truth, narrow AI — which addresses only one task and provides specific results — is growing rapidly, both in power and number of applications (1). Although many different modeling methods remain dominant, AI is providing significant and increasing value in drug discovery, process development,…

Certified Reference Mixtures in Extractables Screening of Polymeric Materials: For Container–Closure Systems and Single-Use Equipment

Plastics have been used for decades in container–closure systems (CCS) for drugs and in single-use (SU) manufacturing equipment for biopharmaceutical processing. Biomanufacturers must comply with national and international laws and regulations that require proof that use of such polymeric materials is safe (1, 2). That necessitates testing for potential biological responses and interactions with drug substances. Comprehensive extractables and leachables (E&L) studies also are required for potential release of undesired compounds from polymers. Extractables tests are performed on materials under…

Regulatory Testing for Cell and Gene Therapies: Meeting the Challenges

Compared with small molecules and other biopharmaceuticals, advanced therapies typically have more complex mechanisms of action and therefore more complex testing requirements. These requirements also change over time as innovators, testing organizations, and regulators apply recent learnings to current projects. When developing a novel cell or gene therapy it is therefore crucial to have a robust, flexible plan for testing your drug. This plan must be sufficient for proving that your drug meets safety standards and other benchmarks, and ultimately,…

The Evolution of Predictive Toxicology: Improving Predictivity Using New-Approach Methodologies

A pharmaceutical’s approval for commercial distribution is contingent on submission of pharmacological and toxicological safety data as defined by regulatory agencies such as the US FDA and ICH. Guidances state that such data can come from in vivo or in vitro studies. The current paradigm works well for collecting critical data about, e.g., a drug’s pharmacological effects and mechanism of action (MoA). However, increasing evidence points to current methods’ inadequacy for predicting a drug’s risks to human patients. Such limitations…

Cold Chain Excellence: Getting Control Over Freezing of Biologics

HOW CONTROLLED FREEZING ENABLES SCALABILITY: Controlling the freezing behavior of drug substance is the ultimate goal in pharmaceutical manufacturing. It opens doors to process reproducibility, consistent quality of the final drug product by maintaining uniform conditions for the biopharmaceuticals during freezing and consequently for frozen storage and shipment. As one of the most essential parameters to achieve control over freezing & thawing bulk, the freezing rate has been considered and evaluated in different tests. The leverage of the ice front…

eBook: Intensifying Processes for Monoclonal Antibodies

The commercial manufacturing success of monoclonal antibodies (MAbs) has become a touchstone of the biopharmaceutical industry. MAbs are so well established that they often are referred to as “traditional” biologics, and well-known MAb processing methods have become a model for processing of other “advanced” or “emerging” therapies. But MAb processing continues to advance as biomanufacturers seek ways to improve efficiencies, lower costs, and (most recently) increase sustainability of facilities. Drug makers are particularly interested in strategies for MAb process intensification.…

Hurdles Ahead for Cell and Gene Therapy Makers

Significant growth of the cell and gene therapy (CGT) pipeline in recent years demonstrates the enormous potential of these modalities to treat or even cure otherwise intractable diseases. Several CGT products have been approved for clinical use over the past five years. More than 75 such products have come to the market around the world so far. They include chimeric antigen receptor (CAR) T-cell therapies that involve genetic engineering of patient cells ex vivo as well as in vivo gene therapies…