May 2014

Development of a Single-Use Filling Needle

Single-use components such as tubing, connectors, and filters have been widely used for many decades in bioprocess unit operations. Users have been able to identify and quantify the specific benefits of single-use over cleanable systems. In more recent years, many other process components have been designed for disposability such as bioreactors, mixers, and chromatography and ultrafiltration systems. Those and other advances have made it possible to incorporate multicomponent, presterilized manifolds into both existing and new processes, realizing benefits such as…

Quality Risk Management for Drug Products and Drug Substances

Risk assessment is used as a vetting tool to determine areas of influence and uncertainty regarding key factors for critical responses. It helps biopharmaceutical companies build both product and process knowledge during development. Every formulation, unit-operation characterization, and design optimization should begin with risk assessment and ends with an understanding of sensitivity, the quantified influence of key factors, improved control logic, edge-of-failure determination, and a qualified design space. Quality Risk Management Quality risk management (QRM) is an essential element in…

The Benefits of Embedding Safety in Lean Practices

The concept of “lean thinking” is applied with increasing frequency in a number of industries, including biopharmaceutical manufacturing, to eliminate waste and optimize workflow. Lean thinking refers to focusing on standardizing processes within workplaces to minimize redundancies and improve value. Safety also is important to every workplace, especially in biopharmaceutical manufacturing because it uses process chemical ingredients. By embedding attention to safety into the practice of lean manufacturing, companies can improve employee buy-in of lean initiatives while reinforcing the importance…

Risk Management in Viral Safety

Recently I spoke with editorial advisor Hazel Aranha (manager of viral clearance and safety at Catalent Pharma Solutions) about viral contaminants and risk management. A recognized expert in the field, Aranha contributed “Current Issues in Assuring Virological Safety of Biopharmaceuticals” to BPI's March 2012 issue and was interviewed by Ellen Martin for her September 2012 article, “Legacies in Bioprocessing.” Spotlight on the Industry BPI: Have there been any recent viral transmission incidents that you can share to highlight the concern…

Rapid Generation of Stable NS0 Production Cell Lines in Chemically Defined Medium

In 1982, authentic human insulin produced in genetically engineered Escherichia coli (under the trade name Humulin, from Genentech) was the first recombinant protein to be licensed by regulatory authorities for therapeutic use. That licensure and the subsequent production of human growth hormone heralded a new era of biopharmaceuticals and were the first examples of the industry's future potential. Both proteins are produced as fully active biologicals in E. coli. Insulin and human growth hormone are fairly simple small proteins, without…

Highly Concentrated Protein Formulations: Finding Solutions for the Next Generation of Parenteral Biologics

Therapeutic protein formulation is no easy task. Biological drugs may be destined for prefilled syringes or glass vials, or they may be made into lyophilized powders that will be reconstituted in a clinical setting. No matter what their final state will be, recombinant proteins must remain potent and efficacious during storage. In recent years, pharmaceutical companies have turned increasingly to high-concentration protein formulations. Such drug formulations can offer patients the convenience of self-injection — instead of a trip to the…

Reference Standards for Therapeutic Proteins

Sponsors developing and manufacturing protein therapeutic products use a number of analytical tests (e.g., cell-based potency and chromatographic assays) to assess quality attributes of their active ingredients and drug products. Tests are conducted for a number of purposes, including characterization, comparability, lot release, and confirmation of stability. This two-part article includes the findings of the California Separation Science Society (CASSS) Chemistry, Manufacturing, and Controls (CMC) Strategy Forum titled “Reference Standards for Therapeutic Proteins: Current Regulatory and Scientific Best Practices and…

Qualification of Scale-Down Bioreactors: Validation of Process Changes in Commercial Production of Animal-Cell-Derived Products, Part 1 — Concept

Implementing continuous process improvements is increasing in priority for the biopharmaceutical industry. Such implementation can be driven by product safety, purity, and stability enhancement opportunities as well as by cost-reduction pressures. Companies invest in projects to improve product quality assurance, safety, and yield as well as production efficiency (1). Such changes may come at any process stage, from early cell-growth methods through final-product packaging improvements. Examples include growth medium optimization, purification column operation optimization, and enhanced recovery during final filling…