Excipients and their Effects on the Quality of Small Molecules
- Excipient challenges
- Alignment of risk based guidance
- Excipient labelling
- Excipient safety
- Biowaiver guidance
- Inactive ingredient list (IIL)
- Novel excipients/safety collaborations
- Case studies
Abstract: The following topics will be discussed in the presentation. There is a lot of risk based guidance that directly or indirectly affects excipient selection, i.e. residual metals (ICH Q3D), residual mutagenic impurities (ICH M7), microbiological contamination (USP and ), GMP (EU/IPEC guidance), etc. However, the output of these different risk assessments may be contradictory with one another or indeed with other major considerations within the target product profile, i.e. cost, complexity, etc. In parallel, the EMA is progressing a major safety based excipient labelling initiative with a particular focus on preservatives. FDA has recently issued two guidances on biowaivers and dissolution that focussed on the impact of certain excipients on bioavailability and hence the ability to use in generic medicines. The FDA has also issued an Inactive ingredient list (IIL) which some commentators have significant reservations about. There is limited impetus by industry in investing in novel excipients. IQ/IPEC are exploring an initiative to de-link the approval process of novel excipients from the approval of the new molecular entity (NME), such that in the event that the NME does not progress important safety data supporting the progression of the novel excipient can still be used. There are also separate collaborative initiatives between FDA and partners, e.g. Lhasa to collate and interpret safety data on excipients. Finally the presentation will use Case studies to reflect some of the common challenges faced during excipient selection.
Former Director of CMC Due Diligence
Technology & Innovation
Leveraging the ADME properties of Peptides for Oral Delivery
• Therapeutic peptides and proteins represent the fastest growing sector of pharmaceutical products.
• Delivery of via the oral route is being investigated by academia and industry alike, as this would significantly improve patient compliance and in some cases, mimic the natural physiological response.
• This has proven to be a highly challenging task as the GIT presents significant barriers to the administration of peptide drugs due to the extensive degradation by the proteolytic enzymes and harsh chemical environment found in the stomach and small intestine as well as the tight junctions between the intestinal epithelial cells that severely restrict passage of large molecules thereby curtailing sufficient oral absorption.
• To successfully overcome these challenges, an in-depth knowledge of the ADME properties of the native peptide(s) and the necessary engineering required to overcome the biological barriers presented is critical in order to achieve sufficient oral bioavailability.
Head of Department Discovery ADME
Technology & Innovation
Manufacturing and Analysis of Coated Amorphous Solid Dispersions and Nanocrystals by Electrospraying
• Amorphous solid dispersions
• Core-shell structured particles
Electrospraying or electrohydrodynamic atomization, has been extensively studied in the past decade for pharmaceutical applications. The relative simplicity, flexibility and efficiency of producing nano- and microparticles, with tailored size, shape, morphology and microstructure, can make electrospraying to become a potential technique in many biomedical and pharmaceutical fields, from improving the bioavailability of poorly aqueous soluble drugs, preparing targeted drug delivery systems and controllable drug release systems to delivering sensitive therapeutic agents such as protein-based drugs or even living cells. Nevertheless, some issues still remain with respect to low throughput as well as the complex interplay between a great number of processing and formulation factors. Understanding of these fundamental aspects is essential for the successful application of electrospraying for the production of particulate formulations with desired properties.
Prof. Guy Van den Mooter
Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences
University of Leuven