Past Event Highlights 2017-2018
MIBio 2018 is organised by the Formulation Science and Technology Group (FSTG) and the Joint Colloids Group (SCI) of the Royal Society of Chemistry (RSC) together with the Academy of Pharmaceutical Sciences (APS). The event will be held on 15th November 2018, Howard Theatre, Downing College, Cambridge, UK.
“5 Years of progress in Oral Biopharmaceutics
“IMI OrBiTo project and global biopharmaceutics research”
The Innovative Medicines Initiative (IMI) ORBITO project is a pre-competitive collaboration between pharma, academia and specialist technology companies which aims to enhance our understanding of how orally-administered drugs are absorbed from the gastrointestinal tract and apply this knowledge to develop new in vitro tests and in silico models that will better predict the performance of oral formulations in patients. For details on this event:
This two-day residential course was aimed at pharmaceutical scientists and regulatory/quality professionals in originator and generics’ companies who would benefit from gaining a better appreciation of key elements in the development and registration of oral dosage forms. The course was pitched at a level suited to pharmaceutical scientists new to the field as well as those wishing to build on and broaden their knowledge. The course material reflected recent changes in guidance/practice. Speakers included key industry and MHRA experts. For past information on this event:
This workshop proved enormously popular when run in March 2017 and was re-run in April 2018. Delegates learnt from a pharmaceutics and biopharmaceutics perspective what is required to assess a molecule in discovery and its suitability for ‘candidate selection’; determining how ‘developable’ it is with associated risk, time and cost implications and what is needed to progress it through pre-clinical studies and into Phase 1 and 2a clinical studies to achieve Proof of Concept. The workshop focused on the formulation and analytical aspects of early stage product development for small molecules for oral delivery in particular and put these activities into context with the other disciplines required to progress an asset. The workshop was interactive with real life examples, lectures and the ability of attendees to raise issues with compounds they are working on. The following topics will be covered: Target product profiles. What properties should a molecule have to be readily developable? (Including solubility, permeability, BCS / DCS classification, Lipinski’s rule, DMPK profile) In-vitro and predictive methodologies: benefits and limitations Overview of preclinical study requirements. Pre-clinical formulations, achieving the desired exposure, species considerations, preparation and GLP Assessment of the API in early development: physical properties, polymorphism, stability, impurities, specification setting Preparing for early phase clinical studies: formulation options, excipients, stability, chemical and physical test methods, manufacture and GMP, regulatory requirements Designing and delivering a Phase 1 clinical programme – considerations, requirements and objectives Next steps: Minding the gap between early and late stage development, QbD, IVIVCs, tech transfer Which CROs and CDMOs can help progress an asset?
On Wednesday 28th March, the APS hosted an event on ‘Accelerating Paediatric Formulation Development’ at the Friends Meeting House in London. This meeting was the chance for the SPaeDD (Smart Paediatric Drug Development) initiative, a co-operation between major pharma companies, leading academic centres and an SME co-funded by the UK government’s Innovate UK scheme, to present progress on how the UK can lead the world in developing better medicines for children. The fifty attendees heard from Sarah Branch and Karin Bracht from MHRA on current paediatric regulations, opportunities for their improvement and the conduct of acceptability and palatability studies. Oscar della Pasqua from GSK and Darren Hargrave from GOSH put the clinicians and patients’ perspective on what is required for paediatric formulations. After the networking lunch when delegates had the chance to view 13 posters, Alastair Coupe from Pfizer, chairing the meeting, explained how these sessions provided a perfect segue to the feedback from the SPaeDD collaboration presented in the second half of the meeting. Catherine Tuleu (UCL, School of Pharmacy) described the SPaeDD work-stream (a collaboration co-led by Terry Ernest of GSK and including work from Afzal Mohammed at Aston University) that had focussed on assessing in-vitro taste testing methodologies aimed at reducing the reliance on taste panels. Catherine’s quote ‘Children DO NOT think that the worse a medication tastes, the better it works!’ sums up the need to develop acceptable paediatric medicines to achieve better adherence. Another repeating message from the meeting was that ‘children are not small adults’ and hence the need to develop paediatric biorelevant dissolution methods and relevant PBPK models rather than simply downsize adult ones. This was the subject of another SPaeDD work-stream the results from which were presented by Jon Brown of BMS (and which was co-led by Nikoletta Fotaki at the University of Bath). Eileen McBride from AZ reported on the various options for taste masking and the results from the SPaeDD work-stream which using the tools reported earlier, had assessed coated multi-particulates (made in Pfizer and Juniper facilities and co-ordinated by Jo Bennett) and cyclodextrin or maltodextrins as encapsulation excipients to mask bitter tasting drugs. Hannah Batchelor (University of Birmingham) described work (with colleague Punam Mistry) to standardise the methodology of assess medicine acceptability in children (aged 2-18) with a hedonic (smiley or sad face) chart being preferred. In the final presentation Andrew Parker explained how Juniper Pharma Services can provide a ‘one stop shop’ for companies wishing to tap into the recommendations from the SPaeDD initiative. Alastair Coupe wrapping up the meeting thanked Anita Jackson who had coordinated the overall initiative, Innovate UK for their funding and underlined what a success the SPaeDD initiative had been and what could be achieved when companies and academia work together collaboratively. For further information go to the SPaeDD website.
Industrial Insights is a two day event for undergraduate and postgraduate students interested in exploring opportunities in the Pharmaceutical Industry. As a student attending the event, you gain first hand insight into the Pharmaceutical Industry through a series of talks by pharmaceutical scientists working within the industry as well as a tour of the Pfizer Research and Development facilities at Discovery Park, Sandwich, Kent. Choosing the right career path…A done deal or still deciding? Industrial Insights 2018 offered opportunities to network with experienced pharmaceutical scientists including members of the NSFG committee, and have your CV reviewed by an industry professional. This meeting takes place every year.
Two-day residential course aimed at pharmaceutical scientists and regulatory affairs professionals involved in the development, manufacture, control or registration of parenteral products. Speakers included key industry and MHRA experts. The aim of the course was to describe the current regulatory requirements, especially focusing on recent changes in guidelines, as well as covering topical issues, trends and developments in the wider field of parenteral products.
Programme
Tuesday 20th March 2018 DAY 1: Product Development, Guidance, Marketing Authorisations & Combination Products
- Session/theme 1 – Development and submissions
- Module 3 requirements and expectations for MAA submissions in the UK and Europe – relevant guidelines and common deficiencies Malcolm Dash, MHRA
- Challenges and barriers to new product development (including experience with using novel excipients) Dr Eddy French, TEKH Consulting
- Process validation – what should be included in the registration submission (small molecule) Cheryl English, Pfizer
- Control of elemental impurities in parenteral drug products – what is the risk? Dr Andy Teasdale, AstraZeneca
- Extractables/leachables Dr Lise Vanderkelen, Toxikon Europe
- The development of ‘age-appropriate’ dosage forms for parenteral administration Dr Catherine Tuleu, UCL School of Pharmacy Panel discussion
Dinner Wednesday 21st March 2018 DAY 2: Session/theme 2 – Drug-Device Combination products
- Dossier requirements and regulatory expectations in the UK and Europe Dr Veronika Ganeva, MHRA
- Requirements for the registration and manufacture of combination products in the US Tim Chesworth, AstraZeneca
- Development of Parenteral Drug-Device Combination Products Following Design Controls Jo Simmons, Pfizer
- Panel discussion
Session /theme 3 – GMP/manufacturing
- Challenges in Clinical Manufacturing of Parenteral Products Joanne Broadhead, Freeline Therapeutics
- Assuring the GMP of excipients used in parenteral products Iain Moore, Croda
- EU GMP requirements for the manufacture of parenteral products – revision to Annex 1 & common deficiencies Alan Moon, MHRA
- QP oversight of parenteral products Simon Morgan, Pfizer
- Panel discussion
- Review FG leads/Chair
MedImmune, AstraZeneca and GE Healthcare Life Sciences, in partnership with GSK, Roche, University of Oxford, BioMax and Academy of Pharmaceutical Sciences held their sixth oligonucleotide networking event. The title of this year’s event was “Emerging technologies in therapeutic oligonucleotides”. The meeting was kindly hosted by MedImmune at their facility in Cambridge and was free to attend. There was a networking drinks reception following the presentations, kindly sponsored by LGC Biosearch. The focus of the 2018 meeting was more in the discovery phase, with four main themes being covered throughout the day:
- CRISPR and Axiomer technologies
- Large molecule oligonucleotides
- Drug delivery
- Analytical and regulatory case studies
The meeting brought together the community of interested professionals and practitioners in industry and academia to network, discuss the latest developments in this field, explore knowledge transfer issues and share best practise.
On 23 and 24 November 2017, the Society for Applied Microbiology joined the Royal Society of Chemistry and the Academy of Pharmaceutical Sciences in responding to the global challenge to help tackle the AMR crisis.
This 2-day conference presented our current understanding of AMR, through key note presentations, case studies, expert opinion, and panel discussions.
Day 1: 23 November 2017
Novel Therapeutics and Drug Discovery, in conjunction with the Academy of Pharmaceutical Sciences
Day 2: 24 November 2017
Antimicrobial Resistance in Wastewater, in conjunction with the Royal Society of Chemistry
- What can we learn from controlling MRSA over the past decade? Jonathan Edgeworth, Department of Infectious Diseases, Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, UK
- Control of catheter associated biofilms through efflux Brian Jones, School of Pharmacy and Biomolecular Science, University of Brighton, UK
- SASPject: a first-in-class antibacterial technology aimed at systemic treatment of MDR infections James Cass, Phico Therapeutics Limited, UK
- Antifungal drug resistance: emerging problems and novel developmental therapeutics Elizabeth Johnson, PHE Mycology Reference Laboratory and National Collection of Pathogenic Fungi, UK
- Lantibiotics: Promising candidates for future applications in human and veterinary health Des Field, APC Microbiome Institute, University College Cork, Ireland
- Antibiotic resistance breaker: reinventing the broad-spectrum antibiotics Miraz Rahman, Institute of Pharmaceutical Science, King’s College, London, UK
- Harnessing nature: alternative treatments for Clostridium difficile infection Gillian Douce, University of Glasgow, Scotland
- Short antimicrobial peptides – their potential to treat bacterial MDR infections Kai Hilpert, Institute of Infection and Immunity, St George’s University of London, UK
- Panel discussion
Cara – a worldwide rescue service for academics and researchers in danger Stephen Wordsworth, Cara Executive Director
Denver Russell Memorial Lecture – Hopes, hypes and multivallate defences against antimicrobial resistance Neil Woodford, AMRHAI Reference Unit, National Infection Service, Public Health England, UK.
This meeting brought together industrial scientists from multi-disciplinary drug product development teams with regulatory scientists and reviewers to discuss new approaches to develop clinically relevant dissolution specifications for oral drug products.
Dissolution testing is the definitive approach to establish the impact of formulation and manufacturing process changes during oral drug product development. Effective strategies for dissolution method development and to establish relevant acceptance criteria are both essential to ensure drug product quality. Currently, during late-stage drug product development, formulation and process parameters are varied to produce so-called ‘aberrant’ formulations which are used to test the ability of a dissolution method to detect changes in oral drug product performance and then often verified in vivo. However, the approaches adopted to create formulations variants which can be considered clinically relevant can be quite diverse and regulatory guidelines for this type of experimentation are not yet clearly defined. Recent advances with in silico mechanistic absorption/PBPK modelling have increased our understanding of in vivo drug product performance and are being used increasingly to support dissolution method development and to establish clinically relevant specifications. This has highlighted the requirement for clinically relevant/biorelevant dissolution data to support model development and the need to increase the general level of understanding and confidence in the modelling of oral drug product performance for this purpose. This meeting contributed to the longer-term goal of the development of a regulatory framework to encompass this rapidly growing field.
This meeting shared case studies from industry which described the approaches used for several oral drug products and feedback on how these were reviewed during regulatory interactions. Regulatory perspectives was provided by regulatory scientists from different agencies and the agenda also reviewed the collaborative initiatives in regulatory biopharmaceutics such as ICH M9 which are relevant to this area. Finally, there was an overview from the IMI OrBiTo programme which described a number of industrial approaches which combine the use of in vitro biorelevant dissolution with PBPK modelling to justify clinically relevant dissolution specifications. The meeting concluded with a roundtable session to review the information shared and debate the options to move this area of regulatory biopharmaceutics forward in the future.
Programme
09:20 – 10:00 Clinically relevant variability and dissolution specifications/overview of ICH –Talia Flanagan (AstraZeneca)
10:00 – 10:40 Dissolution: The Regulatory Perspective Karin Bracht (MHRA)
Presentation abstract:The presentation concentrates on the regulatory data requirements for dissolution studies throughout method, product and process development, to support initial applications for marketing authorisation and later life-cycle management. Approaches to demonstrate the discriminatory nature of the method will be discussed. Considerations for setting clinically relevant specifications will be presented in light of current guidance for both generic and innovator products. Data requirements in support of bioequivalence claims are discussed and BCS and strength waivers are looked at in detail, including the new planned ICH M9 guideline. An overview of differences in BCS waiver requirements between the various regions will be presented. Data requirements for variations and non-immediate release forms, such as prolonged-release and delayed-release will also be presented.
11:10 – 11:50 AstraZeneca Case Study Xavier Pepin (AstraZeneca)
Presentation abstract:Mechanistic absorption modelling using PBPK tools can help support the development of clinically relevant dissolution methods and specifications, justify post approval changes and inform quality by design or LCM development. Several industry examples will be presented where the clinical relevance of dissolution methods was assessed and the information used to support post approval changes, help justify the proposed product specifications or explain some clinical outcomes. The presentation will cover immediate and modified release formulations, the type of methods to integrate dissolution in PBPK and the type of data needed to support mechanistic model building. It will also touch upon the current limitations of the PBPK tools.
11:50 – 12:30 Setting clinically relevant specifications on polymorphic purity in a post-approval environment: a case study Christophe Tistaert (Janssen)
Presentation abstract:During continuous process optimizations, new polymorphic forms of a commercialized drug substance were observed and included a thermodynamically favoured form in the registered crude crystallization solvent and conditions. Consequently, the exclusive production of the commercialized drug substance form could no longer be guaranteed. As part of the mitigation procedure, the influence of the presence of the thermodynamically more stable form on the in vivo performance of the drug product was investigated using a mechanistic absorption model. Based on in vitro characterization and in silico bioequivalence trials of a mechanistic absorption model, clinically relevant specifications on the polymorphic purity of the drug substance and drug product could be supported. The predictions of the model were later confirmed in vivo.
13:30 – 14:10 Integrating in vitro and in silico modelling – OrBiTo experiences Masoud Jamei (Simcyp)
Presentation abstract:Among in silico modelling approaches physiologically-based pharmacokinetic (PBPK) models are increasingly used to address various challenges in drug discovery and development. PBPK models map drug movements in the body to a physiologically realistic compartmental structure using sets of differential equations. Mechanistic oral absorption modelling, which is one of the major applications of PBPK modelling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, drug active pharmaceutical ingredient (API) and the product information, into a systemic mathematical whole-body framework. These models aim at predicting drug products performance in vivo taking into account inter-individual factors. Within a system pharmacology context PBPK models allow separation of the parameters pertaining to the human body (the system) from that of the drug and formulation which is essential to develop generic drug-independent models used to predict the drug products performance in various healthy and patient populations. This framework facilitates integrating information from various sources including data different in vitro biopharmaceutical experiments. Such experimental data can be incorporated within PBPK models in several ways. For example, the solubility data in different media including biorelevant media, dissolution profiles generated in various USP experiments as well as disintegration and release profiles can be used to improve the PBPK models’ predictions. There are challenges in translating in vitro experiment data to in vivo due to differences between the two environments. As part of the OrBiTo grant different approaches for integrating in vitro and in silico approaches were investigated and some of which will be presented and discussed in this presentation.
14:10 – 14:50 Regulatory perspectives (2)
Evangelos Kotzagiorgis (EMA)
15:20 – 16:00 Opportunities and Challenges for establishing Clinically Relevant Dissolution Specifications – an industry perspective Andreas Abend (Merck)
Presentation abstract:The need to establish a clear link between in-vitro tests to assess the performance of pharmaceutical products in development as well as with routine product release has gained significant attention by both regulatory agencies and drug developers. This is evidenced by the many recent publications on the topic of Clinically Relevant dissolution Specifications (CRS). Consequently, a roadmap towards CRS development was proposed by several member companies of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ). This presentation will briefly discuss opportunities and challenges faced by industry establishing the in-vitro in-vivo link via clinical PK studies. The outcomes of such dedicated human PK studies which can resulted in one example in a Level C IVIVC and a second case in an IVIVR will be shown. While these case studies show the significant benefits of establishing clinical relevance of the dissolution method in general, they also have limitations and these will be elaborated.
16:00 – 17:20 Roundtable discussion
Organised by the Formulation Science and Technology Group (FSTG) and the Joint Colloids Group (SCI) of the Royal Society of Chemistry (RSC) together with the Academy of Pharmaceutical Sciences (APS).
This meeting continued on the successful portfolio of amorphous meetings run by the APS to deliver an update on the scientific progress within molecular level control and understanding of amorphous and co-amorphous materials.
Presentations and discussion focused on the significant advances in the design, control and production of amorphous and co-amorphous materials since the last highly successful APS amorphous meeting in 2014. The meeting was organised by the APS Materials Science Focus Group.
There were thought-provoking talks by key opinion leaders, with background from innovator and generic pharmaceutical industrial scientists.
- Professor Thomas Rades-Research Chair in Pharmaceutical Design and Drug Delivery in the Department of Pharmacy, (University of Copenhagen) talked on Co-amorphous drug excipient combinations and formulations
- Sessions were chaired by Professor Yaroslav Khimyak of the University of East Anglia (UEA) and Professor Professor Gavin Andrews of Queen’s University Belfast.
Delegates that attended
- Met the leaders in the field of amorphous phase design, stabilisation and manufacture.
- Learnt about the state of the art in this discipline as these phases mature and move out of academic labs onto the market.
- Took part in discussion sessions that will mould progress in the field.
- Learnt and implemented best practice for the pharmaceutical development of amorphous phases.
Reflections on APS PharmSci 2017 Conference
Date: 5 – 7 September 2017
Location: De Havilland Campus, University of Hertfordshire, Hatfield
Conference Chair: Professor Abdul Basit (University College London)
Theme: Pharmaceutical Science without Borders
A very successful 3-day conference provided an excellent interactive face to face forum for exchange of knowledge and sharing learnings and experiences in many aspects of the pharmaceutical sciences. With 80+ inspiring speakers and over 390 delegates joined together from academia, the Pharmaceutical Industry, and service companies. During the sessions, there was a steady flow of discussion which continued into the breaks and around the exhibition stands and posters.
Young pharmaceutical scientists had their first opportunity to present either a poster or podium presentation (or indeed both!) which is a major strength of APS PharmSci.
Linda Hakes (Retiring APS Chair)
Although I would have loved to attend all three days of PharmSci 2017, unfortunately I had to leave on Wednesday afternoon to fly to Seoul for the FIP Congress. However, Days 1 and 2 of PharmSci were very impressive and all the sessions I attended were of high quality and generated a lot of discussion. The opening plenary lecture by Abdul Basit set exactly the right tone for the conference, describing how an understanding of physiology can improve drug delivery. The second plenary lecture, by Giovanni Pauletti also addressed the conference theme of “Pharmaceutical Science without Borders”, but this time from the angle of international cooperation and collaboration. In the short presentation sessions, I was impressed, as always, by the variety of research that is being conducted in universities and companies, and by the skill of the presenters in conveying their data and enthusiasm in 10 minutes. The future of pharmaceutical sciences is bright!
Mark McAllister (APS Chair)
After a stop-start journey on the M25 on Tuesday morning, I arrived at the conference just before lunchtime and it was good to be back in the familiar surroundings of the University of Hertfordshire. After collecting my badge and updating the conference app (so no bulky bags filled with printed material to lug around this year, all thanks to Helen Barker!!), my conference began with the AGM and Linda presented a great summary of APS activities since the previous year’s meeting. My appointment as the incoming Chair for the Academy was confirmed as were three other board appointments, Julie Cahill joining the board and both Jayne Lawrence and Helen Barker extending their terms of office for a further 3 years. The afternoon scientific programme began with a plenary talk from Professor Giovanni Pauletti who discussed the challenges and opportunities for pharmaceutical education in a world of ever increasingly complex healthcare technology. With this in mind, I opted to attend the Biologics Focus Group session ‘The rise and rise of biotherapeutics’ which provided excellent overviews of the commercial market for advanced biologics and insights into patient preferences for device design. The Black Tie dinner on Tuesday evening at Knebworth Barns was well attended and provided a great opportunity for networking and catching up with friends and colleagues, and included a very entertaining speech from Professor Donald Cairns who had been awarded an eminent fellowship of the academy.
On Wednesday, I attended the plenary lectures from Professor David Jones and Sir Michael Rawlins. In the GSK Innovative Science Award lecture, Professor Jones discussed how innovation in polymer chemistry and processing techniques had resulted in a diverse range of products which ultimately were making differences to the lives of patients and how cross-disciplinary efforts were essential in realising this goal. The lecture from Sir Michael Rawlins, Chairman of the Medicines and Healthcare products Regulatory Agency (MHRA), described how regulatory and clinical trial design innovations could fast-track medicines to patients and also touched on the complex options for regulation in a post-Brexit UK. On Wednesday afternoon, I attended the UKICRS session on ‘Crossing the disciplinary divide for improved healthcare’ which included talks on the development of a polymeric paste for the treatment of malignant glioma, exploiting biological responses with polymer therapeutics and nano-safety research (in which the concept of nanoparticles/human was proposed as a potential risk indicator for endotoxin contamination!). I’m certainly not a subject matter expert in any of these areas but the value in a broad-based conference such as PharmSci is that there is always an opportunity to broaden your knowledge across a range of diverse scientific themes, I certainly learnt a lot from the UKICRS session. Wednesday evening concluded with a bus-trip to the University of Hertfordshire Science Centre and discussions continued over drinks in the lobby and quite a few of the attendees took the opportunity to tour the new labs.
The final day of the conference passed in a bit of a blur for me, as I was busy with chairing the morning and afternoon sessions of the biopharmaceutics IMI OrBiTo presentations. In between these, I enjoyed the plenary presentations from our award winners, Dimitrios Lamprou (RPS Science Award Lecture: ‘Bridging the gap between pharmaceutics and engineering’) and Dennis Douroumis (APS Award Lecture (sponsored by AstraZeneca) – ‘Some like it hot – an extrusion solution to advance drug delivery’). Both presentations reinforced the importance of cross-disciplinary connections and how innovations in other areas (e.g. 3D printing) could provide novel options for drug delivery. As I closed the final session, I reflected on my three days at the conference and I was struck by just how diverse our science base really is. I’ll remember PharmSci 2017 for not just the presentations and plenary lectures but the quality of the posters presented by our younger scientists in the exhibition hall. The organising team (led by Carol O’Connor and John Wahlich) have yet again delivered an excellent conference and on behalf of the board and all our members, I would like to say thank you to all involved!
Don’t forget PharmSci 2018 follows on from FIP World Congress 2018 Glasgow
7th September 2018 Glasgow Hilton Hotel, Glasgow