Pharmaceutical and biopharmaceutical manufacturing relies on the timely and seamless orchestration of many steps to meet aggressive timelines and ensure operational efficiency. A fundamental element of the processing workflow that can impact schedules is the use of multi-ton quantities of bulk raw materials such as buffers, salts and stabilizing chemicals. These raw materials are typically prepared in a just-in-time manner to meet dynamic production needs and enable rapid changeovers.

Octet® systems enable analytical assessment of biologics in various stages of the development workflow beginning with discovery and early selection to validation, manufacturing and quality control. The instrument’s configuration and sample plate format coupled with real-time analysis allows for rapid assay method development. In the last couple of years, Octet® systems have been used by multiple organizations to generate supporting data submitted to various regulatory bodies for the approval of different biologics drug candidates. In addition, Bio-Layer Interferometry (BLI) technology,…

Single-use process technologies have been increasingly incorporated into the manufacturing of biopharmaceutical products over the past two decades. While the reasons for implementing SU systems for biomanufacturing are compelling, there are still some challenges and concerns related to their use. Process automation is often considered one of the weak points of single-use technology. Automation islands are frequent phenomena with SU systems, and integrating the equipment with larger automation systems is challenging. A number of suppliers – like Cytiva, Merck-Millipore, Sartorius,…

Changes in production scale required due to increasing product needs throughout clinical trials introduces risk to the product development timeline. Both the process and the product can be dramatically impacted from scaling-up to larger production volumes due to changes in the bioreactor microenvironment. By “scaling-out,” instead of “scaling-up” these risks can be mitigated. The “scale-out” biomanufacturing paradigm, which involves simply adding one or more of the same-sized bioreactor to the manufacturing run to obtain the production volume required, can also…

Continuous manufacturing (CM) is increasingly used as an alternative to traditional batch manufacturing of solid pharmaceutical dosage forms. Wet granulation is one of the manufacturing technologies that was successfully migrated from batch to continuous processing. Thereby, the residence time of material under (stress) conditions is significantly reduced which in many cases is a main advantage of CM. However, in other cases with slow transformation processes this raises new challenges. In particular, the question arises as to which process parameters and…

The analytical group at Boehringer Ingelheim, Fremont, USA needed a robust assay to measure the biological activity of an antibody fragment (Fab) molecule for in-process testing as well as stability and lot release testing in their Quality Control (QC) department. The developed Fab activity assay is accurate and robust, with intermediate and intramediate precision less than 10%. Drug activity measurement using the Octet® system has become a critical parameter for their product evaluation and has resulted in increased Fab drug…

During formulation of solid dosage forms, film coating is used to improve the appearance and stability of tablets, make them easier to swallow, mask the taste, modify or sustain release, protect the drug from the harsh gastric environment, protect from moisture and/or oxidation and, as a result, to improve the stability and overall therapeutic effect of the final drug product. Depending on the individual needs, a polymer with appropriate properties is chosen during formulation development to serve as film-coating matrix.…

Adenoviral vectors are frequently used as gene delivery tools for various medical applications. In most cases, replication-incompetent adenoviruses are employed, which, once they have infected a target cell, cannot spread further in the patient‘s body. In such applications, regulatory guidelines require that the formation of replication-competent adenoviruses (RCA) in the production process must be minimized. Since the risk of RCA occurrence depends on the adenoviral vector and the cell line used for generating the virus stock and for manufacturing the…

Currently gaining enhanced momentum due to their vital role in the development of vaccines against COVID-19, lipid-based formulations and lipid nanoparticles have shown a lot of promise in drug development and delivery particularly because of their ability to enhance active pharmaceutical ingredient (API) stability by protecting the API from immune response, proteases and other factors; boost the solubility and bioavailability of drugs with poor water solubility; passively target inflamed or tumor tissues due to their leaky vasculature, known as the…

Osmolality testing provides a versatile measure of solute concentration that is an important consideration in the manufacture of gene therapies. This white paper discusses how monitoring osmolality of media during upstream viral vector production and reagents during downstream purification processes can influence quality of the final product. The dependence of multiple biological processes on osmolality, coupled with the usefulness of its measurement in vector quality control, means that osmolality testing is a powerful method to support a high yield of…