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. Since then, there has been continued technological advancement in vaccine development. The resulting platforms provide the promise for solutions for many infectious diseases, including those that have been with us for decades as well as those just now emerging. Each vaccine platform represents a different technology with a unique set of advantages and challenges, especially when considering manufacturing. Therefore, it is essential to understand each platform as a separate product and process with its specific quality considerations. This review outlines the relevant platforms for developing a vaccine for SARS-CoV-2 and discusses the advantages and disadvantages of each.

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. Methods: Case studies are used to illustrate analytical approaches to characterize reference standards, including methods for value assignment, content uniformity, and identity testing. Methods described include NMR, mass spectrometry, and chromatography techniques for identity testing and HPLC and GC methods for assessing peptide content and impurities. Results: This report describes the analytical strategy used to establish peptide reference standard and illustrates how results from multiple labs are integrated to assign a value to the final lyophilized vial. A two-step process for value assignment is described, which uses a mass balance approach to assign a quantitative value to a bulk peptide material. The bulk material is then used as a standard to assign a final value to the vialed material. Testing to confirm peptide identity and to ensure consistency of the vialed material is also described. Considerations for addressing variability, identifying outliers, and implementing stability studies are also presented. Conclusion: The methods and case studies described provide a benchmark for best practices in establishing the preparation, analytical testing, handling, and storage of peptide reference standards for the pharmaceutical industry. Some peptide features, such as chiral or isobaric amino acids, may require additional techniques to ensure a full characterization of the peptide reference standard.

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. To address these needs, the US Pharmacopeia (USP), the Department of Biotechnology (DBT) India, and the Confederation of Indian Industry (CII) held a symposium to discuss the requirements and gaps in the biotechnology and pharmaceutical sectors in India and other developing countries. A panel of experts from academia, manufacturing, and governmental agencies identified several drivers needed for capability building, including a skilled workforce, public–private partnerships, advanced manufacturing technologies, novel biologics, and favorable policies. This article summarizes the recommendations put forward by this panel.

USP's peptide reference standards content is typically determined using an HPLC assay against an external standard for which the purity was determined by a mass balance approach. To explore the use of other analytical methods, the USP Biologics Department conducted a multi-laboratory collaborative study. The study determined the inter-laboratory variability for peptide quantitation using the following methods: HPLC assay, quantitative nuclear magnetic resonance (qNMR) spectroscopy, or amino acid analysis (AAA). The three methods were compared with regard to their suitability for quantitation of the nonapeptide oxytocin. In this study, the HPLC assay method using the same peptide bulk material as the standard showed the lowest inter-lab variability. The coefficient of variation (%CV) was calculated without counting the uncertainty associated with the purity assignment of the standard with mass balance. The proton qNMR method is a direct measurement of the peptide against an internal standard, which is not difficult to perform under common laboratory conditions. Because of the simpler operation and shorter analytical time, qNMR as a primary method for peptide reference standard value assignment deserves further exploration.

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. The quality of these materials is critical for ensuring the safety and quality of the finished therapeutic products. This review will discuss some of the challenges and opportunities associated with the qualification of excipients as well as that of the ancillary materials used in manufacturing.

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. In this study, we confirm that USP's glycan reference standards are compatible with UHPLC by demonstrating comparable peak separation and glycan identification to HPLC methods. The improved resolving power and shorter run-times of UHPLC also allowed us to identify many of the minor glycan components present in USP's glycan reference standards. These more comprehensively characterized glycan reference standards will enable manufacturers to assess the micro-heterogeneity that can negatively impact the safety and efficacy of biological products.