Manufacturing

Automation Solutions for the Efficient Integration of Single-Use Equipment

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,…

7 Key Questions for Understanding the Benefits of Scale-out Biomanufacturing

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…

Material Transformation in Wet Granulation – The Effect of Continuous Process Dynamics, Material and Formulation Properties

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…

Validated Quantitation and Activity Assay of Antibody Fragment Molecule (Fab) for Process Development and Quality Control

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…

Enhancement of Tablet Coating Using an Innovative Functional Excipient

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.…

CAP®Ad – A Versatile Platform for RCA-free, Industrial Scale Adenoviral Vector Production

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…

Successful Drug Development with Synthetic Lipids: Critical Aspects and Strategies

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…

Reagents Matter – Osmolality Testing in Gene Therapy Manufacturing

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…

Ensuring Quality Oversight in Plasmid DNA Manufacturing

The landscape of today’s biopharmaceutical industry is changing rapidly with the introduction of novel drug products, such as personalized medicines. However, while this sector of the market is expected to have a major impact on patient care in the coming years, it also presents significant challenges during development and manufacturing. One such area is a gap in GMP quality plasmid DNA (pDNA) supply, an essential building block for viral vector and even mRNA based vaccines and therapies ― the latter…

Optimizing Control of Pump-Related Biopharma-Production Processes

In biopharma production, pumps are used in a variety of critical processing steps, most notably for liquid transfer that requires the creation and adherence to a required flow rate and pressure level. While this can be done manually through the reading of a pressure gauge and adjusting the motor speed if the pressure should venture outside of the acceptable range, this way is time-consuming and lacks the precision that an automated system can provide. Automated pumps became viable after they…