Advanced Oxidation Processes in Pharmaceutical Formulations: Complex Reaction Mechanisms Triggered by API, Excipients, and Impurities
June 6, 2023, 12:30-2:00 pm ET
The rational design of safe and efficacious pharmaceutical formulations requires a thorough understanding of the mechanisms which lead to chemical and physical degradation caused by various stresses. Degradation pathways may involve a complex network of chemical reactions between the API and excipients. The current webinar will focus on reaction mechanisms responsible for the oxidation and visible light photo-degradation, especially of peptides and proteins, and show how common excipients or combinations of excipients may trigger specific degradation mechanisms. Information gained from these studies can then be used to prevent or minimize such degradation reactions. We will show how certain analytical techniques can be applied for the characterization of short-lived reactive species as well as products, both in liquid and solid formulations. We will focus on reactions of peptides, monoclonal antibodies and other pharmaceutical proteins, and specifically demonstrate how free radical reactions of common buffers, amino acids, and surfactants correlate with the formation of specific degradation products. These include the cis/trans isomerization of unsaturated fatty acids in polysorbate, the site-specific fragmentation within the Fc domain of a monoclonal antibody, and the formation of strongly reducing radicals, capable of peptide and protein disulfide cleavage.
Speaker: Christian Schöneich, Ph.D., University of Kansas
Pharmacokinetics and Toxicity of Oral and Inhaled Cannabinoids
June 8, 2023, 12:30-2:00 pm ET
Cannabidiol (CBD) is great interest for its health benefits and is included in a variety of consumer products. It is primarily consumed via ingestion and inhalation. Little is known about how CBD pharmacokinetics differ between routes of administration, and duration of pulmonary exposure. Lovelace Biomedical performed research in rats on the pharmacokinetics and toxicity of CBD and its major metabolites (6-OH-CBD, 7-OH-CBD, 7-COOH-CBD, and CBD-Glucuronide) after single and repeat dose oral and inhalation administration and found that CBD is more rapidly absorbed and present in higher concentrations following inhalation than ingestion. Plasma levels are also higher following repeated exposure compared to single dose. Metabolites are present in plasma at a much lower level than the parent compound and CBD and some of the metabolites are distributed to the brain. This webinar will discuss respective results in more detail as well as the methods used for the performed research and its relevance for human consumption and potential limitations.
Speaker: Daniela Schwotzer, Ph.D.
Transporter Based Drug‐Drug Interactions: Combining the Power of Endogenous Biomarkers and PBPK Modeling
June 13, 2023, 12:30-2:00 pm ET
The ability to quantitatively predict drug-drug interactions (DDIs) early in drug development is essential to minimize unexpected clinical study readouts and manage the associated adverse risks. Quantitative prediction of drug-drug interactions (DDIs) involving transporter inhibition is limited by uncertainty in the translatability of experimentally measured data (eg., IC50). In this session, speaker will discuss the strategies of leveraging transporter activity biomarkers along with the physiologically-based pharmacokinetic (PBPK) modeling to assess in vivo transporter inhibition risk in early clinical development; and enable better prediction of DDIs and adequately assess clinical risk. Comprehensive studies illustrating the adequacy and utility of endogenous biomarker-informed PBPK modeling in mechanistic understanding and quantitative predictions of organic anion transporting polypeptide (OATP)1B1/1B3-mediated DDIs will be discussed along with selective examples. Current understanding on the biomarkers for other hepatic and renal transporters will also be presented.
Speaker: Matthew Varma, Ph.D., Pfizer
Cold Chain and Transport Validation of Complex Biologic Modalities
June 15, 2023, 12:30-2:00pm ET
Join us for a webinar on cold chain and transport validation of complex biologic modalities, with Gary Hutchinson, president of Modality Solutions, and Robert Battista, Engineering Manager for Modality Solutions. This webinar will focus on how to successfully integrate and validate your biopharmaceutical cold chain for complex biologics. We will present practical insights and strategies to better define your operating space, demonstrate drug product robustness with transport simulation and analytical testing, and align your drug formulation testing with your performance qualification to validate your shipping lanes.
Defining your operating space for drug product requires defining your risks in a formal assessment, understanding the hazards in the distribution network, and combing these two elements into a robust transport simulation test. Coupled with targeted analytical testing, this approach is the most effective and efficient drug formulation testing approach and is considered by many to be an industry best practice.
ASTM D4169 testing is not enough to ensure compliance and safe patient outcomes with complex biologics. Learn an approach that has been proven with regulatory agencies worldwide with over 80+ successful filings in the last four years.
Rob Batista, Modality Solutions
Gary Hutchinson, Modality Solutions
How to Successfully Transition Your Career: Industry and Academia
June 20, 2023, 12:30-2:00 pm ET
In this session, we will discuss the challenges, opportunities and practical approaches required for the successful transition from academics to industry and vice versa. Successful scientists drive pharmaceutical science forward and most of the time their job selection depends on research interest, academic freedom, visa and financial benefit. Maintaining a successful career in academic settings during reduced government grant support is critical. Similarly, maintaining a successful career in the industry driven by the stock market during a recession is critical. While basic research is the focus at universities, applied research is the focus of the pharmaceutical industry. Successful collaboration and transition of manpower between academy and industry are critical for drug discovery and development. There are examples of successful transitions from academics to industry and vice versa, but many people struggle during the transition. Here we would decode the successful transition from both institutions so that many pharmaceutical professionals would be benefitted from such transitions. Additionally, transitions within an institution will be discussed to advise scientists looking to shift their focus, transfer between departments or broaden their scope to a more overseeing role. Various critical factors, including goal setting, networking, mentorship, professional development, grant writing, and teamwork are discussed which are essential for career transition.
Kimberly Lentz, BMSDhaval Shah, Ph.D., Pfizer
Moving the Needle in Veterinary Pharmacology and Comparative Medicine Using Adult Stem Cells Derived Canine Organoids
August 10, 2023,12:30-2:00pm ET
Previously, the use of canine organoids in drug testing and disease modeling was limited to cell lines originating from the intestine, liver, kidney, and urinary bladder. Here, we report the cultivation and molecular characterization of novel adult stem cells-derived canine 3D organoid lines, including the endometrium, lung, and pancreas. Furthermore, we derived and characterized previously reported kidney, bladder, and liver organoids from two genetically related canines. A total of six tissues and organoid lines from each donor were characterized using bulk RNA-seq, allowing for a unique, multi-organ comparison between these two individuals.Tissue-specific genes were identified by comparing the two related donors’ mRNA expression patterns across all six tissues for both organoids and tissues. This database constitutes the most comprehensive multi-tissue comparison made in the canine organoid model to date. With an initial characterization of the epithelial organoid lines, their use in the toxicological field is imminent. Applications of these models range from the use of urinary bladder organoids to assess the carcinogenic effects of environmental toxicants, screening drug candidates for liver toxicity, and studying reproductive toxicology using endometrial organoids, among other applications. Overall, the utilization of canine organoids has the potential to accelerate therapeutic drug screening and be an overall superior model for toxicological research in both veterinary and human medicine.
Jonathan Mochel, Ph.D., Iowa State University
Karin Allenspach, Ph.D., Iowa State University