Analytical

Embedded Particles in Single-Use Bags: Risk to Bag Integrity and Drug Product Purity, or Only a Cosmetic Defect?

When using single-use systems (SUS) to process biopharmaceuticals, preventing drug product contamination from extractables and leachables (E&Ls) and embedded particulate matter (gel particles) in the polymer films used to make bioprocess bags is critical. Using a pressure burst test to assess film integrity, Sartorius Stedim Biotech’s Klaus Wormuth and colleagues compared Flexboy and Flexsafe samples with gel-particle-free materials to assess their potential for contamination. The results showed that only large (2–4 mm2) gel particles affected the burst test results, concluding…

A Faster Solution to Hybridoma Screening

Monoclonal antibodies are a rapidly growing class of therapeutics and are used in multiple clinical indications. This highly competitive landscape necessitates the need for rapidly developing next generation antibodies against new challenging targets with improved mechanism of action and pharmacokinetics. Current antibody screening tools such as ELISA, only report on binding to one antigen target at a time; hence these assays are time consuming and require large amounts of target protein. This case study highlights how the Intellicyt® iQue3 system…

Taking Your Molecule Through Process Validation

The dynamics of the biopharmaceutical industry to get innovative products to the client has evolved over the years. Studies have shown that by 2021, biologics and biosimilar products are projected to have higher growth than other pharmaceutical products. Following the industry trend, Avid Bioservices as a Contract Development Manufacturing Organization (CDMO) has helped numerous clients complete their process validations campaigns. Between 2016 to 2019, Avid has successfully completed six. This custom report will share some key factors to consider for…

Biopharmaceutical Characterization, Part 2: Applications and Strategies for Diverse Products — A Conference Report

Last fall, KNect365 brought together more than 250 analytical specialists to discuss biological assays and characterization of well-characterized biologics in Rockville, MD. Speakers from the US Food and Drug Administration joined experts from leading biopharmaceutical companies, service providers, and consultancies for case studies, regulatory interactions, sharing perspectives, and learning about emerging technologies. Part 1 of this report in January 2019 focused on the bioassay section of the meeting. Here in Part 2 sponsored by Sartorius, BPI’s senior technical editor reports…

Analytical Challenges: Characterization of Oligonucleotide Therapeutics

Recent approvals of oligonucleotide therapeutics are a clear signal for optimism for this product class. This is supported by the strength of the current pipeline which has over 180 active oligonucleotide clinical programs in various phases of development. Improvements in analytical technology and know-how have played a key role in enabling suitable characterization and quality control strategies to overcome the difficulties associated with testing these complex molecules. Despite the lack of dedicated regulatory guidelines related to characterization or quality control,…

Analytical Tools to Improve Decision-Making During Product Development

Speed to clinic testing — and then speed to market — are highly significant metrics for companies developing biopharmaceuticals. By increasing the pace of drug development, these companies can reduce costs, obtain revenues early, and establish commanding positions in the market relative to their competitors. High-throughput development tools have contributed much to the acceleration of drug development in recent years. Such technologies enable the testing of many process parameters in parallel. Combining them with multifactorial “design of experiment” (DoE) analysis…

Visible Particulate Matter in Single-Use Bags: From Measurement to Prevention

Parenteral pharmaceuticals must be “essentially free” from visible particulate matter (1). In the production of biopharmaceuticals with single-use systems (SUS), biocompatibility requires controlling interactions between drug substances/products and SUS surfaces to ensure drug product quality and patient safety with regard to extractables/leachables and particulate matter. Any particulate matter stuck to fluid-contacting surfaces of process components could wash off and contaminate process fluids. Depending on system configuration, a final drug product could be at risk for particulate matter from SUS. Risk…

Emerging Tools for Exosome Purification and In-Process Monitoring

This eBook introduces new analytical approaches that enable in-line chromatographic detection of exosomes. One approach can discriminate extracellular vesicles from nonvesicle contaminants, and one potentially can discriminate exosomes from other vesicles. Examples illustrate how they enable development of more effective and better documented purification methods. The special qualifications of monolithic chromatography media for exosome purification are discussed. New process tools designed to accommodate some of the special challenges of exosome purification are introduced. Exosomes represent one of several species of…

Analytical Strategies for Fixed-Dose Coformulated Protein Therapeutics

Coformulation of two or more proteins in a single formulation is an emerging approach to delivering multiple biotherapeutics that previously have been administered in sequence. This approach brings multiple benefits to all stakeholders. Foremost for patients, the primary benefits are combined therapeutic effects and improved convenience (e.g., fewer administration events). Healthcare providers see logistical benefits and decreased risk of medical errors. Additionally, coformulations also simplify manufacturing logistics, reduce costs of packaging and distribution, and provide new opportunities for product portfolio…

Recommended Practices for Assuring Integrity of Single-Use Systems

The increasing uptake of single-use technologies (SUTs) in critical current good manufacturing practice (CGMP) processes and applications has made their integrity a critical quality attribute (CQA) for both suppliers and end users of such systems. Current regulations focus on final packaging, however, without taking into account the unique aspects of assemblies used in bioproduction. Ongoing initiatives include revision of PDA TR 27 (1) and creation of A STM workstreams (2, 3) to propose good practices for the integrity of single-use…