A number of biopharmaceuticals are enzymes that act in vivo on high-molecular substrates. It can be a challenge to develop in vitro methods for accurately assessing their biological activity. Interest is also developing in using enzyme kinetic parameters as product quality attributes under the quality-by-design (QbD) initiative. Among biotechnology therapeutics, the conventional method of expressing potency is in units/mg of biopolymer. For enzymes, a unit of activity was defined in 1958 by the International Union of Biochemistry and Molecular Biology…
Product Characterization
Rapid Assessment of Vaccine Potency
The global vaccine market is growing annually by 16% and is expected to reach $21 billion by 2010 (1). Much of the predicted growth of this market is expected to come from the introduction of new vaccines, either against diseases for which no vaccine currently exists or as second-generation products to replace existing ones. Much research is still centered on developing vaccines to prevent infectious diseases caused by microbial and viral pathogens. This segment is being fueled by a number…
21st Century Vaccine Manufacturing
Establishment of standard production platforms can help vaccine development move a step closer to the commercial, technical, and regulatory benefits increasingly enjoyed by developers of monoclonal antibody (MAb) products. Three recent advances especially will assist vaccine manufacturing development: rapid analytical methods to support evaluation of process design and provide in-process control; and the establishment of supply chains and vendors across Asia for bioprocessing equipment and consumables that meet the highest international standards. Whereas some workers in the field may consider…
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…