Product Characterization

Assay Validation for Rapid Detection of Mycoplasma Contamination

Mycoplasmas and related bacteria in the class Mollicutes are parasitic organisms found not only on the external surfaces of a wide range of eukaryotic host cells, but also intracellularly. They are characterized by small size and lack of a rigid cell wall, which gives them resistance to β-lactam antibiotics and the ability to pass through 0.2-µm filters (1,2). Contamination by Mollicutes is a common problem for cell cultures that is not easily detected because it usually does not produce turbidity…

Why Do So Many Biopharmaceuticals Fail?

Biopharmaceutials and the processes used to make them are exceedingly complex, and the path to developing new therapeutics is a high-risk endeavor. The emphasis today is on controlling product quality, safety, and efficacy through understanding biological mechanisms, key product attributes, and process parameters. Such information is also crucial for guiding development efforts to improve chances of success in the clinic and for gaining regulatory approval. Analytical methods provide the foundation for acquiring such knowledge. Efforts devoted to developing meaningful and…

“Combine All Files” Maps

Many proteins are regulated by posttranslational modifications (PTMs) such as deamidation, phosphorylation, and glycosylation. Documented effects of PTMs include changes in enzymatic activity, interactions with other proteins, subcellular localization, and targeted degradation (1, 2). Also these physicochemical modifications may also affect receptor binding (3) or higher order structure (4) and result in clinical effects such as changes to bioactivity, immunogenicity, and bioavailability (5). The development of analytical technologies to rapidly interrogate protein structure also has direct relevance to the biopharmaceutical…

Higher-Order Structure Comparison of Proteins Derived from Different Clones or Processes

Biological product manufacture is a complex process that constantly evolves throughout the lifecycle of each product even after its approval. A number of constraints (such as increased yield, scale-up, or a need for greater purity) can necessitate the redesign or optimization of a given process. Heterogeneity of a biopharmaceutical product at the beginning of its shelf life comes from inherent variations in its production process that lead to various forms of posttranslational modifications and degradation products. Clearly, the foremost aim…

Understanding Analytical Methods

As biosimilars move into the forefront of consciousness in the biopharmaceutical industry, analytical methods, especially comparability studies, have an increasingly important role to play. Additionally, as more products progress from phase 1 to 2–3 studies and require production-scale manufacturing, analytical methods are an important component of technology transfer or in-house scale-up efforts. The Analytical Methods for Biologics track will elucidate these challenges, and will include discussions about the latest changes in immunogenicity guidance, posttranslational modifications, analytical strategies, comparability testing, and…

In the Laboratory Automation Zone

When you hear the phrase “laboratory analysis” on a TV commercial, maybe you imagine a technician in a white coat and safety goggles pouring a chemical from one test tube to another. Technicians still wear white coats and goggles, but today, in many labs, they’re not the ones pouring the chemicals. Instead, tiny trays carrying minuscule dabs of samples are whisked by robots from one analytical workstation to another. The workstations are equipped with ultraprecise instrument systems to prepare the…

Current Status of Protein Quantification Technologies

With the help of rapid advancements in molecular biology and genetic engineering, a rising number of biotherapeutics are being developed and marketed. The quality and safety requirements for this class of active ingredients has steadily increased over the decades since Eli Lilly put forth the first insulin manufactured using genetically modified organisms in 1982. This has led to dynamic developments in protein analysis and proteomics intended to meet a growing demand for new technologies and sophisticated analytical techniques to characterize…

Carbohydrates and Their Analysis, Part Two

A polysaccharide is a complex glycan with at least 10 monosaccharide units. It can be formed by the multiples of the same monosaccharide (a homopolysaccharide) or by two or more monosaccharides combined (heteropolysaccharide). Two homopolysaccharides can have completely different conformations — and thus properties — based on the position and type of glycosidic linkages in the structure (Figure 9). Polyglucose ranges from cellulose — β(1,2,3,4) glucan, with its zig-zag chains regularly superimposed to each other and bound tightly by hundreds…

Bioassay Survey 2006–2007

Bioassays are required for a variety of purposes in the development and production of biopharmaceuticals including drug candidate selection, product releases, product stability assessment, and comparability to support proposed process changes. However, because of their complexity and susceptibility to many variables, bioassays often prove problematic and difficult to develop. Timely development of suitable assay systems represents a major investment on the part of the biopharmaceutical industry — but late development often results in even more costly clinical holds. PRODUCT FOCUS:…

Demonstrating Comparability for Well-Characterized Biotechnology Products

Challenges and approaches in demonstrating comparability of a well-characterized biotechnology product after manufacturing changes can be as varied and complex as the products themselves. Participants at the January 2005 CMC Strategy Forum sought to discuss and agree on common implementation strategies for different manufacturing change scenarios. Development of flexible, comprehensive approaches in strategy development addressed evaluation of critical product characteristics, appropriate process steps to test, numbers of lots and levels of testing required, and assessment of product comparability (e.g., trending…