The analytical characterization of recombinant protein therapeutic drug products has broadened to include the use of more sophisticated technologies. The expansion of technical abilities has translated into increasing the depth and breadth of our knowledge and understanding of the drug product intended for commercialization. With the availability of more precise methods, the regulatory expectations for understanding the characteristics of a protein therapeutic drug product are increasing. A thorough understanding of a therapeutic protein’s biochemical and biophysical characteristics is necessary to support investigational new drug (IND) applications and other drug regulatory filings…
BioProcessing Journal Posts
Three types of heart valves are employed for replacement in patients: mechanical, xenogeneic tissue, and allogeneic human valves derived from donors post-mortem. The intention of this article is two-fold: 1) to place issues associated with the preservation of allogeneic human heart valves in perspective relative to the AATB Standards for Tissue Banking and current practices in US cardiovascular tissue-processing facilities; and 2) present potential opportunities for improvements with appropriate validation. Most patients receive either xenogeneic tissue or mechanical valves; however, the use of cryopreserved human valve allografts became established during the 1970s and 1980s for certain patient subsets…
A patent permits the patent holder to keep others out. That is, a patent holder can prevent others from making, using, selling, offering to sell, or importing an invention within the United States and its territories and possessions. In the United States, these exclusionary rights generally last for 20 years from the date on which the patent application was filed. What the patent holder can keep others out of is defined by the “claims” of the patent. Patent claims describe the boundaries of the patent, much like a real property deed outlines the borders of a parcel of land. However, having a patent does not guarantee that the patent holder is free to use the claimed invention…
Electrosprays and electrospinning are two interrelated physical phenomena which have been investigated for well over a century. Their similarity is based upon the primary driving mechanism; namely, the applied electric field. However, they have a fundamental difference that distinguishes one from the other: the former generates droplets while the latter forms continuous fibres. These two processing routes have been extensively researched in many areas. Within the realm of life sciences, these routes have ranged from novel bioanalytical approaches (DNA and biomolecules) to tissue engineering by the formation of scaffolds, which mimic extracellular matrices. Only lately have these methods been explored for the direct process handling of living cells…
Monoclonal antibodies and recombinant proteins have increased in importance and gained success as therapeutic agents in treating various diseases. Biomanufacturing of such a biopharmaceutical product by cell culture follows a main route. Upstream processing is strictly biology-driven, while on the other hand, purification is engineering driven. Fermentation is setting the pace. To some extent, that pace is a result of recent advances in cell culture, greatly increasing the densities of cells along with cell-related contaminants…
When analyzing the complete market for human diagnostic products, with an estimated value of $30 billion annually, the $2 billion market for molecular diagnostic methods is still relatively small. However, with a growth rate of 20% per year, this segment is growing faster than any other in in vitro diagnostics. The reason for this is that healthcare systems have just begun tapping the tremendous potential to which this new technology gives us access. Whereas in the past, large reference laboratories and academic teaching hospitals were the driving force, today the customer base is increasingly made up of smaller diagnostic labs and clinics. Other features of the market are the wide-reaching protection of intellectual property and high product values, due to the significantly higher development and production costs…
Regulatory agencies such as the FDA require the structure and amino acid sequence characterization of recombinant monoclonal antibodies (MAbs) to grant marketing approval. Characterizing such complex, inherently heterogeneous molecules is a significant analytical challenge that requires a broad array of physicochemical tests. Mass spectrometry (MS) is an essential tool for characterizing protein identity, functions, substrate specificity and amino acid sequence (AAS) of recombinant MAb biotherapeutics as it complements, or in some cases supersedes the utility of traditional biological methods. For some of the most important proteomic applications, the high sensitivity and accuracy provided by modern MS has allowed the unequivocal protein characterization…
The aim of personalized medicine is to provide the customized treatment likely to work best for each individual. A narrow interpretation of the definition attributes the appropriate treatment to be based on the patient’s molecular phenotype. A broader interpretation includes cell-based therapies that are derived from a patient’s own cells, or cells from a related or tissue-matched donor. Basic research findings contributing to the knowledge of the molecular and cellular basis of immune-mediated control of cancer and infectious diseases have created opportunities to develop new forms of cell-based vaccination for cancer and chronic infections like HIV. Cell therapy laboratories have developed from their roots in bone marrow transplantation and blood banking into what can now be described as cellular engineering laboratories where cells can be isolated, enriched, transduced, activated, expanded and otherwise manipulated in ways to change or enhance the function of in vivo-derived cells for eventual reinfusion…
The recent discovery of cancer stem cells in leukemia, brain cancer, and breast cancer has had a significant impact on cancer research and how cancers are thought to arise. Their discovery has resulted in unique, but pressing challenges that may ultimately only be resolved through the development of large-scale bioprocesses. The scarcity of these cells is currently impeding discovery of new cancer treatments that specifically aim to eradicate the population of tumour cells thought to be responsible for tumour growth and metastasis. Fundamental bioprocessing principles have been applied to develop scalable, large-scale cultures for cancer stem cells, to address this issue of cancer stem cell scarcity. Development of such bioprocesses differs significantly from other, more conventional cultures since it is the cells themselves that are of interest rather than the products of the cells (e.g., proteins)…
Manufacturers of biological products have come to accept that it makes sense, from both a business as well as a regulatory perspective, to address GMP compliance issues with bioprocessing methods as early as possible in product development. Logically, this same reasoning would also apply to the associated analytical methods used to characterize the product; however, companies still frequently leave methods optimization and validation until later in the developmental timeline which can expose them to unexpected regulatory challenges. In addition, as therapeutics increase in complexity (e.g., cell therapies, transgenics), it raises the likelihood that product characterization will be assessed by novel and increasingly intricate assays—making it difficult to follow a “one size fits all” approach to method selection, development and validation…