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
Biologics – Innovations in Drug delivery
Oral Mucosal Drug Delivery: Current and Future Aspects
- Oral mucosa and immunology
- Oral mucosal delivery systems
- Vaccine delivery
- Drug delivery – regulatory issues
Currently, there are numerous buccal and sublingual delivery products on the market, mostly in conventional dosage forms such as tablets, films, wafers etc.. Efficacy of the small molecules delivered across oral mucosa has been demonstrated to be successful whereas the delivery of the macromolecules has still obstacles to overcome. Recently, sublingual route has been extensively investigated for delivery of vaccines and allergens, consequently good knowledge of the immune cells distributed within the oral mucosal tissue became important. In this presentation, the current status of buccal/sublingual drug delivery will be reviewed, and the possibilities and limitations will be discussed in regard to quality, safety and efficacy issues. Furthermore, the recent studies of our group on oral mucosal delivery of drugs and vaccines will be summarised.
Prof. Sevda Senel
Professor of Pharmaceutical Technology
Hacettepe University, Turkey
Learnings from clinical use of the IntelliCap® system as a tool to evaluate extended release profiles in human GI tract.
• Pros and cons with the Intellicap® system
• In vivo/in vitro correlation of 3 different drug release profiles for a BCS 1 compound evaluated in healthy volunteers
• Case study: using the Intellicap® system to assess regional absorption properties of a development compound
Modified release dosage form development is fraught with risks and it is often also resource intensive, but is occasionally an absolute requirement for the successful development of a drug, e.g. when the intrinsic half-life and pharmacodynamic half-life of an active substance is too short for practical oral administration, or when the drug concentration must be constantly maintained within a tight interval to avoid sub-optimal efficacy and/or toxicities.
Understanding of regional absorption properties of a drug is key to a successful modified release dosage form development and in this talk a convenient method for assessment of regional absorption as well as to rapidly generate in vivo pharmacokinetic data from various drug modified release profiles using the IntelliCap® system will be presented.
The talk will cover data from a clinical study conducted with healthy volunteers using a well-known BCS 1 drug validating the in vivo performance of the IntelliCap® system in man as well as a case study in man with a drug having unknown absorption properties.
Christian Von Corswant
Principle Scientist Oral Controlled Release