Reference Standards to Support Quality of Synthetic Peptide Therapeutics.

Purpose: Peptides are an important class of therapeutics. Their quality is evaluated using a series of analytical tests, many of which depend on well-characterized reference standards to determine identity, purity, and strength.

Objective: Discuss approaches to producing peptide reference standards, including vialing, lyophilization, analytical testing and stability studies.

USP Reference Standard Monoclonal Antibodies: Tools to Verify Glycan Structure.

The glycan profile is a critical quality attribute for pharmaceutical monoclonal antibodies due to the potential physiological impact of the glycan composition when used as a drug product. Monoclonal antibody reference standards are useful as system suitability samples for glycan profile testing. The development of future glycan profiling techniques could be better evaluated by testing well-characterized reference standards.

Biopharmaceutical Industry Capability Building in India: Report from a Symposium.

The biopharmaceutical industry is evolving with a shift in focus from recombinant proteins and antibodies towards more complex cell and gene therapies. To be competitive globally, biomanufacturers need to focus on aligning with global standards with regard to drug quality, reducing manufacturing failures and delivering drugs to market quickly. Building these capabilities requires a multifaceted approach that includes improvements in operations, quality compliance, and control strategies.

Building trust in the quality of vaccines.

To date, several COVID-19 vaccines have been authorized for the voluntary immunization of adults. The quick availability of multiple vaccines is a good strategy to achieve herd immunity during a pandemic. However, the fast-track development of vaccines during this pandemic has raised concerns regarding the quality, safety, and effectiveness of vaccines.

COVID-19 vaccine platforms: Delivering on a promise?

The emergence of the novel SARS-CoV-2 and COVID-19 has brought into sharp focus the need for a vaccine to prevent this disease. Vaccines have saved millions of lives since their introduction to the public over 200 years ago. The potential for vaccination reached new heights in the mid-20th century with the development of technologies that expanded the ability to create novel vaccines.

More comprehensive standards for monitoring glycosylation.

Biologics manufacturers must continually monitor the attachment of carbohydrates, called glycans, to their products, because any variability can impact safety and efficacy. To help the industry meet this challenge, the United States Pharmacopeial Convention (USP) offers glycan reference standards and validated methods for glycoprofiling using high-performance liquid chromatography (HPLC). The industry has recently adopted more advanced technologies for glycan analysis, including ultra-high performance liquid chromatography (UHPLC) and mass spectrometry.

Recommendations for Enhancing Quality and Capability of Indian Biopharmaceutical Industry: Summary of a Workshop.

The biopharmaceutical industry is undergoing an evolutionary phase with the rise of advanced manufacturing technologies. The regulatory and customer requirements are shifting towards the development of personalized or targeted medicines. With this changing landscape, industry must evaluate the relevance of quality management systems.

Do Standards Matter? What is Their Value?

Standards allow us to manage expectations for a diverse range of goods and services across the globe. From coordinating international global telecommunications across 24 different time zones to ensuring access to safe drinking water, standards allow us to work, communicate, collaborate, and live with certain expectations about safety and efficacy. When standards are fit-for-purpose, they raise the quality of products and services without requiring us to think about how that quality is assured.

Cell-Based Therapies Formulations: Unintended components.

Cell-based therapy is the fastest growing segment of regenerative medicine, a field that promises to cure diseases not treated by other small molecules or biological drugs. The use of living cells as the active medicinal ingredient present great opportunities to deliver treatment that can trigger the body's own capacity to regenerate damaged or diseased tissue. Some of the challenges in controlling the quality of the finished cell-therapy product relate to the use of a variety of raw materials including excipients, process aids, and growth promotion factors.

Role of public standards in the safety and efficacy of biologic medicines.

In this report, we emphasize the importance of public monographs with reference materials, coupled with careful process and change control and attention to GMPs, as a means of advancing access to good quality, safe, and effective medicines, with emphasis on available and incoming biologic medicines. With adequate control of articles covered by a monograph, these public standards can form the basis for a global public quality platform that covers reference products, non-interchangeable reference products, biosimilars, and interchangeable biosimilars. Working collaboratively with all stakeholders, new approaches allow these public standards to emerge nationally and globally in a timely way.

Biomarkers in the age of omics: time for a systems biology approach.

Limitations to biomarker discovery are not only technical or bioinformatic but conceptual as well. In our attempt to offer a solution, we are highlighting three issues that we think are limiting progress in biomarkers discovery. First, the confusion stemming from the imposition of a pathology-type immunohistochemical marker (IHCM) concept on omics data without fully understanding the characteristics and limitations of IHCMs as applied in clinical pathology.

No evidence for mouse pancreatic beta-cell epithelial-mesenchymal transition in vitro.

We used cre/loxP-based genetic lineage tracing analysis to test a previously proposed hypothesis that in vitro cultured adult pancreatic beta-cells undergo epithelial-mesenchymal transition (EMT) to generate a highly proliferative, differentiation-competent population of mesenchymal islet "progenitor" cells. Our results in the mouse that are likely to be directly relevant to the human system show that adult mouse beta-cells do not undergo EMT in vitro and that the mesenchymal cells that arise in cultures of adult pancreas are not derived from beta-cells. We argue that these cells most likely originate from expansion of mesenchymal cells integral to the heterogeneous pancreatic islet preparations.

The defined combination of growth factors controls generation of long-term-replicating islet progenitor-like cells from cultures of adult mouse pancreas.

Application of pancreatic islet transplantation to treatment of diabetes is severely hampered by the inadequate islet supply. This problem could in principle be overcome by generating islet cells from adult pancreas in vitro. Although it is possible to obtain replicating cells from cultures of adult pancreas, these cells, when significantly expanded in vitro, progressively lose pancreatic-specific gene expression, including that of a "master" homeobox transcription factor Pdx1.

Generation of islet-like hormone-producing cells in vitro from adult human pancreas.

Transplantation of pancreatic islets can provide long-lasting insulin independence for diabetic patients, but the current islet supply is limited. Here we describe a new in vitro system that utilizes adult human pancreatic islet-enriched fractions to generate hormone-producing cells over 3-4 weeks of culture. By labeling proliferating cells with a retrovirus-expressing green fluorescent protein, we show that in this system hormone-producing cells are generated de novo.

Adult pancreas generates multipotent stem cells and pancreatic and nonpancreatic progeny.

Strategies designed to produce functional cells from stem cells or from mature cells hold great promise for treatment of different cell-degenerative diseases. Type 1 and type 2 diabetes are examples of such diseases. Although different in origin, both involve inadequate cell mass of insulin-producing beta cells, the most abundant cell type of pancreatic islets of Langerhans.