Development Process Technologies: From Bench to Bedside
Maximising Efficiency in the LBP Development Process
From new ways of understanding mechanisms of action, to alternative bacterial enumeration techniques, through to documentation and validation – What are the future methods and technologies likely to be adopted to help maximise speed to market efficiency when taking Microbiotic Medicinal Products from bench to bedside? Below is a preview of the latest developments that will be explored at Pharmabiotics 2019 Conference & Partnering – Register here to join the discussion.
of the Fundamental Mechanisms Underlying Signal Transduction Between the Microbial Species
By Olaf Larsen, Assistant Professor VU Amsterdam & Science Manager Yakult
Although the gut microbiota has been studied intensively for the last decades, the understanding of the fundamental mechanisms underlying signal transduction between the microbial species is still in its infancy. In this lecture, results will be shown that explain these fundamental signalling pathways from a first order perspective using elementary graph (network) theory. Using this approach, the mechanistic rationale underlying the empiric notion that a higher microbiota richness is linked to a more robustness can be elucidated. Moreover, recent results provide ingredients to rationally design fecal transplant analogues, also providing a mechanistic bridge from probiotic single strain to multi-strain preparations.
Olaf Larsen studied chemistry at the VU University Amsterdam and obtained a PhD in biophysics at the same university. Following postdoctoral research in New York City and Amsterdam, he continued his career within industry. Olaf worked for ASML, TNO and as a consultant life sciences within various organizations. Since 2012 he is heading the science department at Yakult Nederland. Since 2016, he is also part time assistant professor the VU University focussing on the valorization of microbiota management.
Cytometry as an Alternative Method for Probiotic Viability Measurement
By Martin Wilkinson, Associate Professor at the University of Limerick
Viability of bacteria is traditionally determined by plating of samples on to agar media with enumeration of resultant colonies following growth. This methodology is slow, labour intensive and only enumerates bacteria based on their growth under specific environmental criteria. It is evident that an alternative rapid, high-throughput viability methodology is urgently required, especially for commercial probiotic cultures, probiotic supplements and foods into which probiotics are added. The probiotics industry has responded to this need by employing Flow Cytometry (FCM). This methodology enables rapid analysis (< 5 mins for prepared stained samples) of individual bacterial cells enabling differentiation and enumeration of cultures into sub-populations of live, damaged or dead cells. Multi-parametric data is generated from FCM analysis of fluorescence generated from single cells stained based on their morphological or physiological properties. Using combinations of stains with FCM allows a unique insight into probiotic cell viability and vitality (functionality). This presentation will review the evidence for FCM as an alternative for rapid bacterial viability determination and will focus on a novel IDF/ISO FCM-based method developed by the probiotics sector based on a tri-staining method. Overall, FCM offers an alternative rapid methodology for determination of viability and vitality of probiotic cultures.
Martin Wilkinson is Associate Professor in Food Microbiology at the University of Limerick, who has established a research programme in the application of flow cytometry to the study of food bacteria. This has led to an output of a significant number of peer-reviewed publications in the field with research funding secured from national and international agencies. Martin commenced his work on the development of cytometry methods to study the permeabilisation and enzyme-release properties of Lactic Acid Bacterial starter cultures. This research has expanded into other areas of food pathogens and spore forming bacteria with the use of cell sorting to gain an insight into microbial physiology during food processing and storage. Martin’s most recent publication is a landmark independent review commissioned and funded by the International Probiotics Association on the potential of flow cytometry as a method of measuring bacterial viability in probiotic products. Martin is also the editor of a seminal text on microbial flow cytometry published by Caister Academic Press in 2015.
Keeping Up-to-Date with Guidelines
By Frederique Vivielle, Founder & CEO, 5-QBD Biotech
Many guidelines affecting the development and manufacturing of Live Biotherapeutic Products (LBPs) are currently in draft form or have just recently been published. Working on the changes in advance of publication is crucial: firstly, to be ready once applicable and second, to mitigate risk. This presentation will focus on some of the most important upcoming guidelines including:
- European Pharmacopea – LBPs (Live Biotherapeutic for Human Use) – Draft March 2017-
The requirement for LBPs regarding traceability of the strain from the Research, “Sterile” media and control of the Product are now clear.
- Annex 1 – GMP- : Manufacture of Sterile Medicinal Products – Draft Dec 2017-
Thinking that the Annex 1-GMP concerns only sterile products is a big mistake. The principles of this guideline should be led to control the contamination risk: What about the “Aseptic Simulation Process”?
- EU n°536/2014 – : Good Manufacturing Practices for IMPs for Human use– Draft Dec 2017-
No more any doubt on the regulatory requirements for IMP (Investigational Medicinal Products), such as Traceability of changes, Qualification and the Release Chain.
Frederique acquired a multi-disciplinary vision of the Drug Development, from Research to Regulatory submission after more than 15 years experiences in Pharma/Biotech companies. After obtaining her Pharmacist graduation, she started in a French CDMO, producing and developing solid forms for commercial market. She passed the graduation “Engineer in Biotechnology” and became Head of QA – QP Deputy in a Swiss company for sterile products in clinical phases. Then, Frederique covered all the Pharmaceutical chain as Quality Director in a UK start-up developing LBPs. Frederique founded 5QBD-Biotech (Quality Business Development) to secure and speed up any Drug Development and Manufacturing process.