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  • Biologics - Innovation in Drug Delivery
  • Biologics - Optimising Drug Formulations
  • Small Molecules
  • Technology & Innovation

 

Day 1 – Monday 27th March 2017
07:30-08:20
Registration & Light Refreshments

08:30-09:10
Keynote Address
Technology & Innovation
Opening Keynote: The Changing Landscape of Biotherapeutic Development

Image result for pfizer

  • Current trends in Biotherapeutic Portfolios
  • New Technologies for Delivery and Manufacture
  • Device Design and Delivery Challenges
  • Focus on the Patient

Biologics continue to increase in prevalence and value in the world-wide marketplace. Additionally, the biological therapies continue to become more complex and competitive, both by modality and delivery. Cell-based immunotherapies, gene therapies and vaccine based immunotherapies are examples of the increasingly complex landscape we are faced with developing. Along with the complexity of the therapies themselves, supply chains, costs and patient friendly devices are challenging established systems and development paradigms.
Devices have become increasingly important for the success of biologic products. Patient administered therapies are commonplace around the world and are adapting rapidly to the diversity of modalities and formulation challenges. Devices are becoming key enablers of successful biologic therapies and design control and the patient interface are integral parts of the development process.
Patient focused formulation and drug delivery is increasingly important to the success of the development process and needs to be considered as an integral part of primary development plan.

Ron Peeples
Vice President, Pharmaceutical Sciences, BioTherapeutics
Pfizer

09:10-09:15

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Session chairs
Small Molecules – Olaf Queckenberg, Head of Global Chemical & Pharmaceutical Development Bayer Pharmaceuticals Division Germany
Biologics – Patrick Garidel, Director Pharma Development, Biopharma Boehringer Ingelheim Germany
Technology & Innovation – Manoj Koranne, ‎Director R&D W.R. Grace USA
09:15-09:50
Case Study
Small Molecules
Advancements in the Development and Manufacturing of Nanosuspension Based Drug Products

novartis-logo

Several nanoparticulate drug products joined the market in the last decade with commercial success. More recently, generic copies of originator products joined also the market demonstrating attractive and promising business areas. However, strategic drawbacks and technical limitations are nonetheless obvious to extract the inherent capabilities of nanosuspension based drug products. For instance: When should be a nanosuspension approach selected for a poorly soluble compound? Do we have realized the potential of nanosized drug compounds? Do we have elaborated future drug product manufacturing strategies to enable continuous manufacturing and patient centric approaches? The presentation will provide an overview on the currently commercialized nanosuspension based drug products, and will mainly focus on the following topics to address current strategic drawbacks and technical limitations:

  • In vitro rank ordering of formulation concepts from enabling technologies at the early stage of development.
  • Perspectives and first successes for drug nanoparticles below 100 nm particle size.
  • Continuous manufacturing of solid oral drug products with flexible dose strength using liquid dispensing and forced drying technology.

Michael Juhnke
Senior Fellow Oral Pharmaceutical Development Novartis AG
Switzerland

Case Study
Biologics – Optimising Drug Formulations
Considerations for the Development of Highly Concentrated Protein Drug Products
boehringer4web
Definition of highly concentrated protein formulation
What is high?
Challenges from manufacturing, to analytics, device to stability
Some case studies

Patrick Garidel Director Pharma Development, Biopharma
Boehringer Ingelheim
Germany

Case Study
Technology & Innovation
Continuous Processing of Solid Oral Dose Forms
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  • Traditional concepts of batch processing have given way to new paradigms in continuous processing for the manufacturing solid oral products. This transition from batch manufacture to continuous, flow-through systems requires development of new technologies, devices, procedures, control systems and release strategies. This requires a new understanding of both the theoretical and practical aspects of the most common unit operations and redefines the way products are developed and commercialized. This presentation will provide an overview of the design and development activities within Pfizer that led to the development of continuous processing systems and at the same time adapting them to target commercial products. The examples shown should provide insight to both the conceptual understanding of continuous processing systems and the data-driven approaches that were fundamental to the development of Pfizer’s portable, continuous processing module.

George Sienkiewicz, Ph.D.
Senior Manager
Pfizer Inc.

09:50-10:45
iSolve Meetings, Meet the Speakers & Refreshment Break
 iSolve-Logo-resized
10:45-10:50
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10:50-11:25
Case Study
Small Molecules
A New and Versatile Method for Preparing Drug Nanoparticle Formulations for Enhancing Bioperformance
Image result for merck sharp and dohme
• Crystalline drug nanoparticle formulations are well established as an option for improving oral absorption of poorly soluble compounds. Nanoparticle formulations also can be used effectively for IV and IP administration routes. This flexibility makes nanoparticles particularly useful for studies in preclinical species.
• Nanoparticle formulations historically have been prepared by high energy milling processes that require substantial amounts of drug. This limits the use of nanoparticles in discovery space, where compounds are typically available only in small quantities. A stabilizer is generally required to prevent the nanoparticles from agglomerating.
• Here we describe an innovative method using a commercially available high-frequency mixer that enables the preparation of nanoparticles at scales from a few mgs to kgs. The method also is easily adapted to a multiwall plate format that allows for high throughput stabilizer screening. These advantages enable nanoparticles to be used for evaluation during the drug discovery stage all the way to the preparation of nanoformulations for the clinic.

John Higgins
Senior Principal Scientist, Discovery Pharmaceutical Sciences
MSD

Case Study
Biologics – Optimising Drug Formulations
Viscosity Reduction and Injectability of Highly Concentrated Protein Formulations

novartis-logo
Viscosity and injectability of highly concentrated protein solutions is currently a hot topic for the pharmaceutical industry due to the increasing need to deliver high doses subcutaneously. Ongoing studies at Novartis Biologics are tackling this issue. In particular:

    • We have shown that it is possible to correlate the viscosity of highly concentrated protein solutions to injectability if the rheological properties of the solution at high shear rates are well characterized.
    • Some additives can reduce the viscosity of highly concentrated protein solutions.
    • The effect on those additives on viscosity at high shear rates was for the first time investigated.

Those results will be presented and discussed.

Ahmed Besheer
Group Head NBE Formulation Development
Novartis

Case Study
Technology & Innovation
Continuous Manufacturing – Critical Steps and Possible SolutionsImage result for tu graz

• Optical Coherence Tomography (OCT)
• Chemical Imaging via NIR
• General Control Strategy
• Model Simplification

The ability to change pharmaceutical production from predominantly batch manufacturing to a modern, fully-integrated continuous-manufacturing-based supply chain model is becoming reality. Several companies have started to bring continuous lines online. Regulatory agencies have approved the first products sold in USA and Europe. However, there are several challenges still involved. First, several unit operations do not exist in continuous mode, such a fluid-bed granulation. Second, lines are designed for “easy” materials. Thus, novel solutions for complex materials (high electrostatic chargeability, poor flowability, tendency to segregate, etc.) need to be found, or at least, a material design space needs to be developed. Third, novel sensors need to be developed in a robust manner to be suitable for real-time quality control. Moreover, modern control concepts based on a mechanistic process understanding need to be utilized. In addition, economic models are needed that demonstrate the superiority of continuous plants, also including criteria such as flexibility and supply chain risks. Lastly, novel regulatory approaches are needed, e.g., for batch definition or for real-time release testing. In this talk these topics are discussed and possible solutions are highlighted. Moreover, the International Institute for Advanced Pharmaceutical Manufacturing (I2APM) and the European Consortium for Continuous Pharmaceutical Manufacturing are presented.

Prof. Johannes Khinast
Head of Institute for Process & Particle Engineering
TU Graz Austria

11:25-11:30
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11:30-12:05
Technology Spotlight
Small Molecules
Eyes on AQOAT® HPMCAS for Solid Dispersion

  • Listen to the originator
  • Solid dispersion: Hot melt extrusion and down stream processing
  • Adjusting AQOAT® to the process:Medium particle size.

Andreas Sauer
Technical Manager
Shin-Etsu

Technology Spotlight
Technology & Innovation
Introduction to VPA (vaporized peracetic acid) sterilization; A new path to innovation and efficiency.

Revox web

Traditional sterilization methods, such as ethylene oxide (EO), gamma radiation can leave behind dangerous carcinogenic residuals or even damage and degrade a product’s materials or packaging. REVOX has developed a room-temperature sterilization process that uses Vaporized Peracetic Acid (VPA) to gently sterilize all surfaces of a product within its package. This patented technology has excellent penetration capabilities, and leaves behind no residuals. VPA breaks down into relatively harmless, naturally occurring substances: water, oxygen, and carbon dioxide. The safety and easy installation of the REVOX VPA system provides manufacturers the ability to add efficient in-line sterilization to their manufacturing process. VPA has been verified safe and effective for use on over 100 materials, including thermoplastics, adhesives, bio-absorbables, metals, and more, and has been approved as the sterilization method on a FDA 501(k) approved Class II medical device. VPA sterilization makes it possible for manufacturers to safely disinfect products without exposing them to high temperatures, moisture, radiation, or hazardous chemical byproducts. Learn more about VPA, its applications, and how it can work for you.

Mason Schwartz
Inventor of REVOX VPA technology & Director of R&D and Operations
REVOX Sterilization Solutions

Technology Spotlight
Technology & Innovation
Mesoporous Silica: A Drug Delivery Platform for Solubility Enhancement

Grace will present a detailed discussion of the mechanisms of silica for solubility enhancement for BCS class II drugs. We will introduce effective methods of particle engineering of compendial silicon dioxide to create stable amorphous dispersions.
Specific discussion will include:
  • Case studies demonstrating technology efficacy
  • Practical considerations for scale up and formulation development
  • Benefits of this technology for transfer to clinical trials
Additionally, Grace will demonstrate the value creation of using compendial silicon dioxide for drug delivery.

Fred Monsuur
Global Excipients Commercial Development Manager
Grace

12:05-12:10
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12:10-12:45
Case Study
Small Molecules
Non-invasive Drug Delivery across Epithelial Barriers for Combatting and Preventing Infectious Diseases
hips
Biological Barriers impede the transport of drugs fron the site of administration to the site of action. For non-invasive (“needle-free”) delivery, the body’s outer epithelia – intestines, skin and lungs – are of particular importance. In the context of inflammatory and infectious diseases, they might even represent relevant therapeutic targets by themselves. In addition, the efficient delivery of antiinfectives faces some peculiar barriers. These include biofilms, which hamper the access to extracellular bacteria, the membrane of host cells hiding intracellular bacteria, and finally the bacterial cellular envelope itself. This presentation will highlight some of our recent work in this area, concerning both new in-vitro models and new drug carriers systems, for which the nano-size often has turned out to be advantageous.

Prof. Claus-Michael Lehr
Head of Department Drug Delivery
Helmholtz Institute for Pharmaceutical Research (HIPS)

Case Study
Biologics – Optimising Drug Formulations
High Throughput Chemical Denaturation And Relative Viscosity Measurements Via Fluorescence During Formulation Development

Sanofi logo

    • High Throughput Early and Late stage Pharmaceutical Development
    • Predictive analytics for therapeutic protein
    • Viscosity
    • Thermodynamic Stability

During early and late stage pharmaceutical development of therapeutic proteins, an extensive physicochemical characterization of different candidate molecules and formulations is required. The identification of the best candidate or formulation can be facilitated by studying the thermodynamic stability and the relative viscosity profiles.

  • Chemical denaturation measurements enable computation of the thermodynamic stability (ΔG0) of the candidate molecule. The method is based on the chemically induced protein unfolding, which can be monitored via fluorescence spectroscopy.
  • Similarly, relative viscosity measurements are performed by measuring the fluorescence of an extrinsic molecule, whose fluorescence properties are sensitive to the viscosity of the formulation.
  • Both methods enable screening of several candidates in a few hours by using low volumes (~100µL, up to 128 formulations, n=3).

Riccardo Torosantucci
Head Lab Formulation Development, Biologics
Sanofi-Aventis Deutschland Gmbh

Case Study
Technology & Innovation
Delivering the Promise of Continuous Secondary Manufacturing
Image result for gsk logo transparent

• Drivers for continuous secondary OSD
• Technical barriers for implementation
• TSG case study ( residence time distribution and process understanding examples)
• Proposed focus areas for future platform evolution

The pharmaceutical industry is under tremendous pressure to change. For manufacturing and product development, industry is striving to deliver :
• Enhanced product quality, quality assurance and process robustness
• Small flexible manufacturing footprint at low cost and environmental impact
• Minimised development and technical transfer costs and resources.

This has driven a move towards continuous OSD manufacturing. This presentation will review drivers for change, some of the technical barriers to implementation with reference to a TSG case study. It will conclude with a perspective on areas for focus in the future.

Richard Elkes
R&D continuous secondary OSD engineering lead
GSK

12:45-13:40
Networking Lunch

Lunch During lunch, a specially moderated round table discussion will be lead by:

Omya Logo CMYK (jpg)

Direct compressible mineral ODT platform: Omyapharm ODGs

 

Orally Disintegrating Tablets (ODT) are getting increasingly popular drug delivery systems allowing better patient compliance, especially in the case of pediatric, geriatric, psychiatric patients. In addition, they are also interesting for product life-cycle management and for marketing purposes. Omyapharm ODGs provide your formulation with the following benefits:

  • Very fast disintegration time
  • Excellent compactability
  • Ready-to-use
  • High drug loading
13:40-13:45
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13:45-14:20
Case Study
Small Molecules
Right Time, Right Place; Exploiting Micro and Nano Particulates for Drug Delivery

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• Development of sustained release of small molecule and peptide APIs to shift treatment from daily to monthly or longer
• Delivery of hard-to-formulate actives for complex and novel applications
• Poly-lactide microspheres for the treatment of eye diseases
• Organ-selective delivery of cytotoxic payloads
• Targeting of tumour cells

Precise and intelligent application of particulate technologies can address drug delivery challenges and facilitate the development of products with novel characteristics that benefit patients. Specifically, the ability to transform daily injections in to monthly, quarterly or longer and the delivery of therapeutics directly to the target organ, thereby shifting the therapeutic window and making drugs safer and more efficacious. By re-defining the approach to production of polymeric microspheres we discuss a unique level of control, accelerating the formulation development process and designing-in novel characteristics. Exemplified by non-toxic sustained delivery of therapeutics for the treatment of back-of-the-eye diseases, we show how poly-lactide based particulates can facilitate new therapies to address substantial unmet need. We go on to present data on unique, ultra-small gold nanoparticle conjugates that are designed to deliver cytotoxic payloads to specific organs and the targeting of tumour cells, particularly in liver and brain cancers. Summarising how particulates can be exploited to address clinical needs, improve existing therapies and facilitate new ones.

Tom Coulter Senior Vice President, Research Midatech Pharma Paul Seaman
Head of Sustained Delivery
Midatech Pharma

Case Study
Biologics – Optimising Drug Formulations
Formulation Design for Biologics in the Age of Lab Automation and Biological Performance Screening

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Current challenges due to new molecule formats
Impact of lab automation and data management on formulation screening
Advanced Formulation Development

Michael Siedler
Head of NBE Formulation Development – NBE Formulation Sciences & Process Development
AbbVie Deutschland GmbH & Co KG

Case Study
Technology & Innovation
Thermodynamic Stability of Amorphous Solid Dispersions

Image result for technische universität dortmund

API solubility and crystallization in ASDs
Thermodynamic vs. kinetic stability of ASDs
Influence of humidity on ASD stability
Amorphous-amorphous phase separation
Influence of additives

Abstract:
Amorphous formulations in which an active pharmaceutical ingredient (API) is integrated in a polymer matrix are often thermodynamically unstable. Therefore, unwanted amorphous-amorphous phase separation and even API crystallization might occur during storage. These two phenomena are caused by the thermodynamic phase behaviour which itself is influenced by the kind of API and polymer, by temperature, and by relative humidity.
Due to this complexity, suitable formulations are so far usually found by trial-and-error procedures. Thermodynamic understanding and modeling of the underlying phenomena, however, is a valuable tool to improve and to intensify this process.
The talk will give an overview about the thermodynamic phase behaviour of ASDs. All phenomena will be discussed on the basis of experimental data for various systems. Finally, it will be shown that thermodynamic modelling today allows for reliable correlations and even predictions of the ASD phase behaviour. It can thus drastically reduce the experimental effort for developing the optimal API formulation and its processing.

Prof. Gabriele Sadowski
Professor Thermodynamics, Department of Biochemical and Chemical Engineering
TU Dortmund

14:20-14:25
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14:25-15:00
Technology Spotlight
Small Molecules
MicroJet Reactor Technology: A Novel Approach for Nanotechnology Reformulation
Image result for leon nanodrugs
  • More than half of all marketed therapeutic drugs are poorly soluble or practically insoluble in water. However, good water solubility is a pre-requisite that drugs are taken up into the body and distributed to the desired sites where they can unfold their therapeutic potential. This vital problem in drug development can be solved by using nanotechnology.
  • The proprietary and patent-protected MicroJetReactor (MJR) technology by leon-nanodrugs is a classical bottom-up approach for nano- and microparticle synthesis. Basis of the process is a continuous solvent / non-solvent precipitation that is performed under very well controlled process conditions.
  • The particle size is well controlled and can be adjusted using the flow rates of solvent and non-solvent, as well as type of solvent and stabilizer. The reactor is operated in a continuous way and allows a production capacity up to 600 l/h.
  • leon-nanodrugs is the exclusive licensee of the MicroJetReactor technology platform for pharmaceutical applications and develops drug products based on nanoparticle & nanoemulsion approaches.
Elke Horstkotte
Senior Project Manager
Leon Nanodrugs

Technology Spotlight
Technology & Innovation
New possibilities using AFFINISOL™ excipients Exploring a platform of tailored polymers for solubility enhancement

AFFINISOL™ polymers are uniquely tailored to address solubilization performance requirements. Several case studies will be presented:

AFFINISOL™ for Spray Dried Dispersions

  • HPMCAS products with a broad range of release properties
  • Creating an amorphous dispersion via top spray-granulation

AFFINISOL™ HPMC for Hot Melt Extrusion

  • New cellulosic materials maintaining the crystallization inhibiting properties of traditional HPMC, but can be extruded over a wide temperature range without the use of plasticizers

Next generation of AFFINISOL™

  • Innovative cellulosics and non-cellulosics based excipients addressing solubility challenges

Meinolf Brackhagen
Senior Scientist, Pharma TS&D
Dow Pharma Solutions

Technology Spotlight
Small Molecules
Formulating Amorphous Solid Dispersions: Bridging Particle Engineering and Formulation

  • Critical aspects in the downstream processing of amorphous solid dispersions
  • Impact of spray dried material properties in final dosage forms production and performance
  • Optimisation strategies for downstream processing of amorphous solid dispersions

João Henriques
R&D Team Leader
Hovione

15:00-15:05
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15:05-15:40
Case Study
Small Molecules
Lipid Suspensions – An Approach to Increase Oral Bioavailability or just Greasy Business?

Image result for janssen
• What is a lipid based suspension and how could it look from a commercialisation perspective?
• When can lipid based suspensions be used to improve the oral bioavailability?
• How large a proportion of the compound needs to be solubilised in the lipid phase?
• What excipients to use for lipid based formulation?

The oral route of administration is the most convenient route with respect to drug delivery and patient compliance. However, many new drug entities on the market are poorly water-soluble drugs, belonging to class II in the Biopharmaceutics Classification System, which present a challenge to oral delivery due to their often poor solubility in the gastro intestinal fluids, resulting in a poor oral bioavailability. To overcome this hindrance the use of lipid-based drug delivery systems such as lipid suspensions may offer a great potential for enhancing the solubility and bioavailability of the poorly water soluble compound.

Lipid suspensions have been described in older literature, but not many newer studies is availbe. This presentation will discuss the potential of lipid suspension in general and present a larger data set with two model compounds where both fraction solubilised and lipid type is variable parameters. The excipients investigated include both hydrophilic and lipophilic excipients frequently used in lipid based formulations, which was dosed to rats.

The data demonstrated large differences among the investigated excipients, where as low as 25% of the dose produced a relative bioavailability at the same level as when all compound was solubilised by the lipid excipient. The data clearly demonstrate that it is possible to enhance the bioavailability of low water soluble compounds when administered as a suspension compared to a solution. Especially excipients with long-chain lipids demonstrated a higher performance compared to medium-chain lipids. This indicates that the structure of the excipient, as well as the interplay between drug and excipient, have an effect on the absorption and bioavailability of the compound.

Rene Holm
Scientific Director and Head of Drug Product Development, Parenterals and Liquids
Janssen Pharmaceutica Belgium, Johnson & Johnson

Case Study
Biologics – Optimising Drug Formulations
Typical challenges and pitfalls in the formulation and clinical application of ADCs and BITE molecules


Very high potency of ADCs and BITEs (specifically: stimulation of the immune system of BITE molecules and application of MABEL Approach
Need for robust formulation of complex mixtures of highly active compounds (ADCs)
Very low starting dose in the clinical trial (stability and compatibility issues)
Complex handling procedure and preparation in the clinic for very low concentrations (BITEs

Antibody Drug Conjugates (ADCs) and Bispecific T-cell engager (BITE) molecules are highly potent and bioactive molecules for the treatment of cancer. The bioactivity is based on different mechanisms leading to specific challenges.
Since the ADCs are often a mixture of antibodies conjugated in different ratios to linkers and toxophors, the challenge is the stabilisation and handling of such a complex mixture of bioactive molecules (having slightly different physico-chemical properties like solubility & hydrophobicity) and the handling of very toxic toxophores.

BITEs show also a very high bioactivity, based on the activation of the immune system and the involvement of T-cell activation and cytokine release.
Therefore, very low starting doses in the dose range finding study are required following the MABEL approach (Minimal Anticipated Biological Effect Level). These doses in the ng/ml range are challenging with respect to the compatibility assessment with systems needed for preparation and application of the highly diluted bioactive solutions and the transfer and alignment of such procedures into the clinics, where clinical trials are performed.

Dr. Carsten Olbrich
Senior Scientist External Technology & Innovation
Bayer AG Germany 

Case Study
Technology & Innovation
Formulation of Amorphous Solid Dispersions – From Physical Chemistry to Bioavailability

uni_copenhagen

  • Amorphous solid dispersions
  • Drug solubility in polymers
  • Spring and parachute effect
  • In vitro in vivo correlation
  • Overcoming challenges in downstream processing ASD powder

Amorphous solid dosage forms are one of the most promising formulation strategies to overcome the limited bioavailability of many poorly water soluble drugs. However, the industrial application of amorphous solid dosage forms is still rather limited. This is likely to be due to an insufficient understanding of the physico-chemical properties of amorphous solid dispersions including their physical stability, as well as due to the lack of predictive in vitro models. In this presentation, in the first part, methods to predict the drug–polymer solubility at room temperature will be discussed, to determine the concentration of drug dissolved in a polymer below its saturation solubility (i.e. formation of a stable glass solution). In the second part of the presentation we will focus on the question how both the in vitro and in vivo performance of amorphous solid dispersions is influenced by the drug dose and polymer type in amorphous solid dispersions.

Prof. Thomas Rades
Research Chair, Pharmaceutical Design and Drug Delivery Department of Pharmacy
University of Copenhagen

15:40-16:40
iSolve Meetings, Meet the Speakers & Refreshment Break
iSolve-Logo-resized
16:40-17:15
Case Study
Small Molecules
In Vitro Strategies to Predict Oral Bioavailability

uni_copenhagen

• Different in vitro models – for different stages of drug development
• How complicated does a predictive in vitro method need to be?
• Which are the critical parameters to simulate – for which formulation?
• When is an in vitro lipolysis model needed?

Anette Mullertz
Professor, Department of Pharmacy, Faculty of Health and Medical Sciences
University of Copenhagen

Case Study
Biologics – Optimising Drug Formulations

Formulation and Process development of ADC Drug Products -A Case Study

novartis-logo
• Physicochemical properties of ADCs and its implication on DP development
• Stability challenges and lessons learned from ADC formulation development
• Product stability testing under clinical in-use conditions and setup of a clinical procedure for first in human studies
• Development and optimization of a generic freeze-drying cycle for ADCs

The CMC development of ADCs can be regarded as an extension of current MAb development strategies, and standard MAbs are further processed in order to attach cytotoxic payloads. This extension impacts resources and time required for process development (conjugation, formulation, and analytics), the complexity of these processes as well as the final product. Developing stable formulations for ADC drug products is particularly challenging. The balance between physical and chemical stability, and hurdles associated with the administration of the material in the clinics can impact the development of ADCs and render it more complex than for standard MAbs. The presentation shall provide insights into drug product development of ADCs at Novartis including (1) Stability and formulation challenges (2) analytical development (3) DP stability testing under clinical in-use conditions and (4) freeze-drying cycle development.

Daniel Schweizer, Ph.D.
DP Project Lead TD NBE’s

Novartis Pharma AG

Case Study
Technology & Innovation
Progress in Understanding and Control of Amorphous Solid Dispersions

Image result for abbvie
Amorphous solid dispersions play a key role among today´s enabling technologies for poorly soluble drugs. Examples are given, how progress in amorphous solid dispersion formulation development, increasing understanding of its drug release and stability, as well as insights into the extrusion manufacturing process have contributed to make amorphous solid dispersions by hot melt extrusion a mature established drug delivery technology.

Bernd Liepold
Group Leader, Senior Principal Research Scientist
AbbVie Deutschland GmbH & Co. KG

17:15-17:20
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17:20-17:55
Case Study
Small Molecules
The Impact of Cancer Drug Target on Formulation and Manufacture

UStrathclyde

  • Traditional chemotherapy – drugs and targets
  • Formulation approaches
  • The identification of new cancer drug targets
  • Development of new formulation and manufacturing strategies
  • Problem of Pharmaceutical mass customization

The advent of cancer chemotherapy in the late 1940’s is linked to the observation that mustard gas induced myelosuppression which may useful in the treatment of lymphoma coupled with the identification of folic acid which increased the growth of tumours when administered to leukaemia patients. Both effects were linked to DNA and this stimulated research to develop improved drugs with increased anti-cancer activity. The majority of these agents were small molecules and the key formulation challenges revolved around solubility, stability and delivery to patients suffering from multiple types of cancer. At the turn of the century the discovery of imatinib, which specifically blocks the activity of the bcr-abl oncogene revolutionised cancer chemotherapy. The new agents were designed to specifically block an oncogene linked enzyme pathway, had an increased molecular weight, therefore solubility remained as a formulation challenge with the added complication of low bioavailability by the oral route. This restricted treatment to those whose cancer’s contained the relevant oncogene, thus limiting patient numbers. In combination with these scientific developments the regulatory and financial landscape was also changing. This juxtaposition of science, regulation and cost is an interesting direction of travel that will necessitate novel approaches to ensure patient benefit.

Prof. Gavin Halbert
Director, Cancer Research UK Formulation Unit
Strathclyde Institute of Pharmacy and Biomedical Sciences

Case Study
Biologics – Innovation in Drug Delivery
Infusion set compatibility and drug delivery challenges of high potency ADCs

immunogen

• Hydrophobic nature of conjugated cytotoxic agents makes confirmation of ADC compatibility with infusion sets challenging.
• Compatibility of ADCs with infusion set materials and diluents used for drug delivery can be product specific and must be thoroughly studied on a case by case basis.
• Low concentration ADCs usually bind to infusion set surfaces (e.g. in-line filters, tubing and bag) resulting in poor drug recovery.
• Analytical methods may need to be re-developed for testing low concentration ADCs.

Antibody-drug conjugates (ADCs) manufactured with hydrophobic cytotoxic agents are significantly different in their biophysical properties than the corresponding unconjugated monoclonal antibodies (MAb). The hydrophobic cytotoxic agents may lead to non-specific interactions with materials used in drug delivery systems (e.g. intravenous administration sets, in-line filters, tubing, bags). Solubility in common diluents (e.g. saline or dextrose solutions) can be limited resulting in precipitation or surface adsorption. This presentation will discuss several case studies about compatibility of ADCs with a variety of commercially available infusion set materials. The challenges and approaches related to testing and compatibility assessment of the diluted ADCs will also be presented.

Pui-King (Amy) Leung
Scientist I Analytical and Pharmaceutical Sciences
Immunogen Inc.

Case Study
Technology & Innovation
Amorphization by Co-Milling

150px-Sanofi.svg

  • Formulation screening
  • Manufacturing process feasibility study
  • Manufacturing process scaling-up Nowadays, most of drugs entering development are poorly soluble in both aqueous and organic media. Consequently, their bioavailability after oral or parenteral administration is very limited, and very often, below the therapeutic level. This hurdle excludes the conventional approaches (e.g. solubilisation in a surfactant) of overcoming the above mentioned issues arising due to the poor drug solubility. In recent decades, there has been an increased interest in the use of solid dispersion as promising approach to overcome the drug solubility issue.
  • This presentation is focused on the formulation and process engineering by co-milling.

Mostafa Nakach
Head of Pharmaceutical Engineering Sanofi
France

17:55-18:00
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18:00-18:35
Keynote
Technology & Innovation

Utilizing Novel Technology to Accelerate Drug Development, Save Money and Improve the Efficiency of Drug Delivery and Formulation
Ferring4web

a. How technology & Processes effect Development Costs and Speed:

    • Technology / Innovation (Continuous manufacturing, Throughput & automatization
    • Operations and Processes (Front/Backloading and sourcing/prioritization model, In/Outsourcing)

b. Technology & clinical output and/or competitive advantage

    • Describing a technology push approach via internal and external tech platform CoEs for driving novel peptide and protein drug development and LCM of marketed drugs.

c. Realization of opportunities in specific (emerging) markets)

  • Presenting the structural, operational and technological set-up of internal Technology platform CoEs and strategic external partnerships
  • Case studies involving different technologies (e.g. controlled peptide release via polymers, sublingual gels, or others) while explaining the competitive advantages
  • Increasing importance of “connected drug delivery systems”, combining diagnostics with drug delivery for tailored dosing.

Georg Schmies
VP, Global Head Product Development & Drug Delivery at Ferring Pharmaceuticals
Ferring Pharmaceuticals Denmark

18:40-20:00
Evening Reception

Day 2 – Tuesday 28th March 2017
07:30-08:00
Registration & light refreshments

08:05-08:40
Opening Keynote Address
Technology & Innovation
Utilization of Prior Knowledge to Modernize Product Development

Image result for Texas A&M Health Science Center

Providing case each from the topics below to show what happens when we develop a formulation without fully understanding the science.

• Oral delivery of biologics – bioavailability, modelling and innovative drug delivery systems
• Injectability of highly concentrated protein formulations
• Understanding and control of amorphous solid dispersions
• Nanoparticles – preparation, progress and future potential
• Challenges of paediatric drug delivery
• Microneedles and the latest transdermal delivery systems

Dr. Mansoor Khan
Vice Dean
Texas A&M; Health Science Center (Former Director, Division of Product Quality Research, FDA)

08:40-09:15
Session chairs
Small Molecules – Olaf Queckenberg, Head of Global Chemical & Pharmaceutical Development Bayer Pharmaceuticals Division Germany
Biologics – Patrick Garidel, Director Pharma Development, Biopharma Boehringer Ingelheim Germany
Technology & Innovation – Manoj Koranne, ‎Director R&D W.R. Grace USA & Brigitte Illel, Head of Skin Delivery Platform, Sanofi France
Case Study
Small Molecules
Implant Design for Ophthalmic Delivery: The place of Materials and Fabrication Methods

UStrathclyde

    • Implants introduced into the intravitreal or intracameral space offer the possibility of long term management of intraocular disease
    • The physical presentation within the eye poses difficult questions in terms of interference with vision
    • The vitreous humour of the elderly is very different to that seen in juveniles or in animal models
    • The consequence: altered clearance- suggests a reassessment of the approaches in ocular management of glaucoma and age related macular degeneration

Unlike the gut, the eye undergoes profound changes on ageing. Many of us live into frail old age, when degenerative changes have occurred and perhaps ophthalmic surgery such as cataract surgery will have occurred. In order to preserve our remaining sight, we need to receive therapy on a chronic basis. The ocular space is well protected and therefore sterile medications may have to be introduced which deliver the active principle over a long period. The age-related changed will affect clearance and selection of an inappropriate mode of delivery may cause unwanted issues or risk being ineffective. The selection of materials available as the matrix for modulating delivery is narrow but even subtle changes to polymer structure alter release properties. Excluding gels, the appropriate ‘scale’ of ocular devices is within the nano and micro range, which suggests exciting possibilities for novel methods of fabrication.

Prof. Clive Wilson
J. P. Todd Professor of Pharmaceutics
Strathclyde University

Case Study
Biologics – Optimising Drug Formulations
CMC Development of ALKs Fast Dissolving Tablets for Sublingual Allergen Immunotherapy.

Image result for alk abello

    • Life-cycle management strategies for a new product generation of specific allergy vaccines
    • Identifying a tablet technology suitable for a biological product
    • Characteristics of biological HDM (House-Dust Mite) allergen extract
    • Process innovation to solve a scale-up challenge

Specific allergy vaccination using allergens as the active ingredient (allergen immune-therapy) is currently the only treatment for allergic patient that relieves the symptoms and at the same time treats the cause of the disease. Traditionally, allergy vaccines have been administered subcutaneously, using aluminium hydroxide as carrier and adjuvant in combination with the allergens. ALK has for a number of years worked on developing a new generation of allergy vaccines using a tablet formulation that is administered through the sublingual route. The aim of this presentation is to give insight into the CMC development of these new allergy vaccines including how to overcome scale-up challenges of a HDM (House-Dust Mite) allergen tablet through process innovation.

Christian G. Houghton
SVP, Global Head CMC Development
ALK-Abelló A/S

Case Study
Technology & Innovation
Drug Delivery from a Novel Co-Suspension™ Metered Dose Inhaler – Evidence of consistency, robustness, and patient-use reliability
pearl

• To meet regulatory requirements, orally inhaled products must have consistent in vitro delivered dose and aerosolization properties.
• Achieving consistency at the time of manufacturing, during storage, and during various scenarios of patient use has been a significant challenge for combination products, which must have the same drug delivery performance between mono and dual products.
• Pearl Therapeutics has developed a novel pressurized metered dose inhaler formulation technology that combines micronized drug crystals and a porous particle excipient to form a stable Co-SuspensionTM
• This Co-Suspension™ Technology allows for the development of a fixed-dose combination of the potent bronchodilators glycopyrrolate, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting  2-agonist (LABA), with consistent and robust drug delivery regardless of time, storage, or condition of testing.

Jon Schroeder
Director Pharmaceutical Development
Pearl Therapeutics (a subsidiary of AstraZeneca)

09:10-09:15
Please move to your next session

09:15-09:45
Case Study
Small Molecules
Application of Quality by Design in Continuous Processing Systems
Image result for pfizer

The development of continuous processing systems within Pfizer has required the broad research and manufacturing organizations to define a Quality by Design operating philosophy. As continuous systems for solid oral products continue to transform all the activities that typically comprise pharmaceutical development and commercialization, Pfizer has formulated a general approach comprised of product/process development, real-time monitoring platforms, advanced manufacturing control systems, and wide use of various modeling applications. This presentation will provide an overview of how these QbD elements come together and result in robust, understandable and predictable products and processes.

George Sienkiewicz, Ph.D.
Senior Manager
Pfizer Inc.

Case Study
Biologics – Optimising Drug Formulations
Molecular Stability of Vaccine Antigen – Case Studies

Image result for sanofi pasteur

    • Thermal impact on molecular stability
    • Molecular dynamic as a tool to understand protein stability
    • Prediction of stability by degradation kinetic modeling
    • Formulation simulation to improve stability

Presentations will focus on how de-risking stability issue and associated formulation with experimental design and dedicated predictive tools developed for complex biomolecule systems formulation. Main focus will be: 1) 1 how we can solve the formulation development paradox, e.g. short development and quick results to insure a long term stability, 2) how we can predict and formulate proteins in silico when e.g. experimental approach is limited , 3) how we can predict with sufficient validity, stability from accelerated data. This will be illustrated by case studies of stabilization of antigenic protein, adjuvanted glycoprotein, and lived attenuated virus for which preformulation and marketed product formulation should assume the better continuity for time to clinic trials and market optimization.

Olivier Brass
Formulation Scientist
Sanofi Pasteur

Case Study
Technology & Innovation
Solid Solutions and the Oral Absorption Frontier

Image result for merck sharp and dohme

  • Solid solutions are widely applied and have had a profound impact at MSD and elsewhere in promoting oral absorption of water insoluble drugs
  • Experience with solid solutions has begun to uncover aspects that appear to fundamentally limit what is possible with oral drug absorption
  • Solid solutions have enabled the amelioration of food effect and absorption variation association with changes in stomach pH (e.g., achlorhydria)

Abstract: The application of solid solution technology has expanded the developable chemical space and enabled drug delivery for challenging drug targets—particularly in the infectious disease area. While routine application of solid solution technology has been reduced to practice at many pharmaceutical companies today, the limits that define their applicability remain largely unknown. The fundamental limits of solid solution application appear to be tied directly to our understanding of drug “speciation” in vivo. Recent work characterizing nanoparticle formation as the result of liquid-liquid phase separation has provided one basis from which we can start to define the oral absorption frontier. Recent late stage and commercialized products have clearly demonstrated other aspects of future frontiers for solid solution products—including amelioration of food effect and the impact of elevated stomach pH on the oral absorption of basic drugs.

Dr Craig Mckelvey
Distinguished Formulation Scientist
MSD

09:45-09:50
Please move To Your Next Session

09:50-10:50
iSolve Meetings, Meet the Speakers & Refreshment Break
iSolve-Logo-resized
10:50-11:25
Case Study
Small Molecules
In Silico Formulation in Pharmaceutical Development

Sanofi logo

    Nowadays, it’s possible to calculate many key properties of drug substances which are critical for drug product development.This lecture will demonstrate that prior calculations/molecular simulations of drug substance properties can allow increasing the development success to accelerate the path to clinical formulation. Special case studies will be presented such as:

  • Solubility, which play a crucial role in the early development
  • Compatibility and stability of drug substance in formulation
  • Drug loading in some complex enabling drug product, nanoparticle/amorphous dispers

Philippe Lienard CMC Discovery Coordinator
Sanofi France

Case Study
Biologics – Innovation in Drug Delivery
The Mucus Gel Barrier: Industrial applicable strategies to overcome it

Logo_Uni_Innsbruck

The enemy’s strength: Structure and composition of mucus
Passive and active mucus permeating micro – and nanocarrier systems
Results of various in vivo studies: What do they teach us?
How to make your delivery system mucus permeating utilizing just GRAS excipients

Mucosal membranes are coated by a mucus gel layer consisting of mucus glycoproteins that are connected with each other via disulphide bonds. For most drug delivery systems mucus represents an often underestimated barrier, strongly reducing drug bioavailability. Strategies aiming to overcome the mucus gel barrier, however, are mainly based on the breakdown of the mucus gel layer over almost the entire mucosal tissue being from a toxicological point of view highly problematic as the mucus layer has a substantial protective function. Within this talk an overview of alternative and industrial applicable strategies focusing especially on micro- and nanocarrier systems capable of permeating the mucus without destroying it is provided. Generally mucus permeating carriers can be divided into passive and active systems. Passive systems try to avoid as many interactions of micro- and nanocarriers with mucus as feasible. The likely most promising systems are carriers exhibiting a slippery surface and self-emulsifying-drug-delivery-systems (SEDDS). In contrast, active systems interact with the mucus making it leakier for carriers. These systems are mainly based on disulphide bridge breaking agents and on proteolytic enzymes. Furthermore, carriers changing their zeta potential from negative to positive once they have reached the epithelium seem to be promising and are currently in development.

Andreas Bernkop-Schnürch
Head of Institute Pharmacy
Universität Innsbruck

Case Study
Small Molecules
Recent Progress in Understanding and Predicting Oral Absorption with Focus on the IMI project OrBiTo
AstraZeneca.svg
    • A general overview of the OrBiTo project as being the most extensive research effort in oral biopharmaceutics area in the world
    • A review of key results of human mechanistic studies revealing novel insights in gastro-intestinal physiology and oral drug absorption
    • Selected results from extensive validation work performed on in vivo predictive in vitro and in silico methods including use of a novel cross-company database with historical PK/biopharmceutics data
    • Discussion on implications of progress for product development

OrBiTo is an on-going IMI project (http://www.imi.europa.eu/) in the area of oral biopharmaceutics tools that include world leading scientist from nine universities, one regulatory agency, one non-profit research organisation, three small/medium sized specialist technology companies together with twelve pharmaceutical companies. The OrBiTo project will deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies or refinement of existing tool. Extensive validation will be performed of novel and existing biopharmaceutics tools by using historical datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of gastrointestinal drug absorption. This approach gives an unparalleled opportunity to deliver transformational change in European industrial research and development towards model based pharmaceutical product development in accordance with visions of Quality by Design. Benefits include an accelerated formulation development process, particularly for challenging projects e.g. for low solubility molecules (BCS II and IV) or modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, it will significantly reduce the need for future animal experiments in this area and reduce the need for human bioequivalence studies for bridging between formulations within clinical programmes. About 60 papers have been published so far from OrBiTo (http://www.orbitoproject.eu). The present lecture will provide a selection of significant findings and achievements obtained so far.

Bertil Abrahamsson
‎Senior Principle Scientist
AstraZeneca

11:30-12:05
Technology Spotlight
Small Molecules
Exploring the Influence of Excipient Variability on Functional Related Characteristics

DFE

  • Increasing emphasis in excipient reproducibility
  • Quality by design of excipients
  • Functional related characteristics of excipients

Dr Bastiaan Dickhoff
Senior Product Application Specialist
DFE Pharma

Sander van Gessel
Product Manager Lactose
DFE Pharma

 

Technology Spotlight
Biologics – Optimising Drug Formulations
Paradigm Shift: The Importance of Closing the Characterisation Gap between APIs and Formulation Components

Pfanstiehl 200

  • Quantitation of elemental impurities at levels well beyond ICH Q3D requirements is important to formulators who need to understand the aggregate functional contribution of many components on the drug product
  • Sucrose, Trehalose, Mannitol, and Galactose are often used at relatively high concentrations in upstream media, downstream purification, and final formulation. It is often assumed that minor fluctuations in low level impurities and/or variability among manufacturers will have minimal impact on overall bioprocess robustness and product quality. In fact, the potential for unforeseeable impacts of a variety of impurities such as glucans, endotoxins, elementals, reducing sugars, and particulates is heightened when non-quantitative methods are used to characterize these materials.
  • The need to treat such functional components as APIs, especially in terms of characterization and process control strategies will be discussed.
  • Case studies of how product quality issues have been resolved through thoughtful quantitative characterization of critical components will be presented.

Christian Lotz
Director, Business Development
Pfanstiehl

Technology Spotlight
Biologics – Optimising Drug Formulations
Unleash Automated Buffer Exchange
UNCHAINED-LABS-Logo_large
  • Early-stage formulation screening to formulation development
  • Buffer preparation, exchange and analysis in one portfolio
  • Impeccable mass recovery
  • Analytical data supports protein handling equal to or better than dialysis and Amicon centrifugal devices

Quincy Mehta
Product Manager
Unchained Labs

12:05-12:10
Please move to your next session

12:10-12:45
Case Study
Small Molecules
Excipients and their Effects on the Quality of Small Molecules

Image result for gsk logo transparent

  • Excipient challenges
  • Alignment of risk based guidance
  • Excipient labelling
  • Excipient safety
  • Biowaiver guidance
  • Inactive ingredient list (IIL)
  • Novel excipients/safety collaborations
  • Case studies
  • Conclusions

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.

David Elder
Former Director of CMC Due Diligence
GSK

Case Study
Biologics – Innovations in Drug delivery
Oral Mucosal Drug Delivery: Current and Future Aspects
Image result for Hacettepe University, Turkey
  • 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

Case Study
Small Molecules
Learnings from clinical use of the IntelliCap® system as a tool to evaluate extended release profiles in human GI tract.

Image result for astrazeneca

      • 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
      • GI transit times
      • 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
AstraZeneca R&D;

12:45-13:45
Networking Lunch

Lunch During lunch, specially moderated roundtable discussions will be held on:

Identifying the Best Formulation Strategy for Poorly Soluble Compounds

  • How to speed up a new Nano or HME technology approach from screening to the final dosage form?
  • How can nanosuspensions been used for parenteral applications ?
  • How to stabilize HME formulations to achieve also good in-vivo properties ?
  • Aspects to consider working with innovative technologies
  • DoE and QbD approaches in early development phases
  • Application of potent and high potent drugs

Losan web 2

13:45-14:20
Technology Spotlight
Small Molecules
Accelerated Formulation Development for Poorly Soluble Drugs and Modified Release Products

Quotient web

Advancing a drug delivery concept into a viable product can be a lengthy and costly process, compounded by non-clinical screening models frequently failing to accurately predict outcomes in humans resulting in multiple cycles of product development and optimisation. An integrated formulation development, manufacture and clinical testing model can overcome many of these challenges and accelerate the development of both simple and complex drug delivery projects. The integrated approach is both efficient as well as flexible, allowing a development team to make adjustments to further optimise a product or respond to new considerations / risks identified as new data emerges.

This presentation will discuss:

  • Formulation development processes to promote bioavailability for poorly soluble drugs, and to modify the shape of the PK profile for modified release
  • Constraints of current formulation development processes
  • Benefits of real-time adaptive product manufacturing
  • Rapid formulation development and optimisation strategies
  • Case studies in solubility enhancement and modified release formulation development

John McDermott
Executive Director, Drug Product Optimisation
Quotient Clinical

Technology Spotlight
Biologics – Optimising Drug Formulations
Extending Drug Half-Life to Achieve Monthly Dosing? The Potential of Veltis® Engineered Albumins for Optimized Dosing

albumedix web

Short circulatory half-life represents a major obstacle for many protein and peptide-based therapeutics. This can be significantly improved by conjugation or fusion to albumin, due to increased size and recycling via the neonatal Fc receptor (FcRn). The increased FcRn affinity of the Veltis® engineered albumins translates to more than doubling of the already long half-life of native albumin. We will describe rationally engineered albumins and their application to improve the pharmacokinetic properties of therapeutic candidates.

Joanna Hay
PhD Customer Solution Science Manager
Albumedix

Technology Spotlight
Technology & Innovation
Transdermal Delivery Systems (TDS): A Complex, but Manageable Dosage Form
Druck
  • Criteria to select an API as candidate for TDS
  • How to select ingredients for a TDS and how to develop a TDS using QbD
  • Scale up from lab trials to the manufacturing department – One of the LTS strengths

Dr Thomas Hille
Director, Research & Development
LTS Lohmann

14:20-14:25
Please move to your next session

14:25-15:00
Case Study
Small Molecules
Stabilization and Comparison of Manufacturing Techniques for the Production Nanocrystalline Suspension by Top Down Process
150px-Sanofi.svg
● Formulation engineering
● Process engineering
● Modelling for prediction and simulation

Mostafa Nakach
Head of Pharmaceutical Engineering Sanofi
France

Case Study
Biologics – Optimising Drug Formulations
Leveraging the ADME properties of Peptides for Oral Delivery
Image result for novo nordisk
• 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.

Stephen Buckley
Head of Department Discovery ADME
Novo Nordisk

Case Study
Technology & Innovation
Oral Drug Delivery: What to learn from Imaging Studies. An update

Image result for uni-greifswald.de

Gastrointestinal dynamics
Imaging
Fluid volumes
Food effects

Many concepts of oral drug delivery are based on an interpretation of human gastrointestinal conditions as a beaker glass filled with a more or less complex fluid. This understanding is corroborated by compendial dissolution apparatuses where dynamics is mostly interpreted as the rotational rate of a stirring device. This understanding ignores the complex interplay between the various physiological factors in the human gut and in particular, the dynamics of transit conditions to which oral drug delivery systems and released drug material are exposed. Recent advances in spatial and temporal resolution of medical instrumentation as well as improved access to these technologies provides fascinating insights into the dynamic processes within the human gastrointestinal tract. Such studies show the high dynamics of parameters like fluid volumes, dosage form movement and pH values in the GI tract.

Prof. Werner Weitschies
Head of Department Biopharmaceutics and Pharmaceutical Technology
University of Greifswald

15:00-15:05
Please move to your next session

15:05-15:40
Technology Spotlight
Small Molecules
Technology Spotlight
Oral Delivery of Live Bio-therapeutics: Drug product development for FIM studies
Quay Pharma web
  • Current landscape (who is working in the area/therapeutic indications/current knowledge base)
  • Regulatory (Where do live-bio-therapeutics sit)
  • Handling and containment
  • Contamination and decontamination
  • Formulation and processing considerations examples of early case studies
  • Analytical/micro testing,
  • Specification setting (examples and considerations)

Mike Frodsham
Pharmaceutical Development Manager
Quay Pharma

Technology Spotlight
Technology & Innovation
Technology Spotlight
PVA – Revival of a long lost polymer: Drug Solubility Enhancement and Modified Release
Merck logo correct

Polyvinyl alcohol (PVA), a non-toxic polymer, has a long history in the pharmaceutical industry. In our research work, we developed PVA, not only to improve aqueous solubility of poorly soluble drugs using solid dispersion technology, but also as a matrix polymer to modify release kinetic of final dosage form.

Dr. Finn Bauer
Director of Solid Formulations R&D
Merck KGaA

Technology Spotlight
Technology & Innovation
Meeting Todays Drug Delivery Needs With New Polymer Technologies

Ashland_Master_4color_PMS2

  • Challenges in drug delivery and dosage form development and critical importance of excipients
  • Areas of focus in polymeric development: extensions of existing chemistry for solubility and processability enhancement
  • New HPMCAS Analogs: Improved Thermal Processing for Hot Melt Extrusion and improved throughput in Spray Drying Operations

Christian Mühlenfeld
Technical Leader Pharmaceutics, Europe
Ashland

15:40-16:30
Networking & Refreshment Break

16:30-17:05
Case Study
Small Molecules
Co-amorphous materials, discovery and design
200px-Durham_University_logo_svg
      • What are co-amorphous materials
      • Potential approaches for co-amorphous screening
      • Potential property improvements within co-amorphous phases
      • The curse of hydration behaviours
    • How can they be used

The amorphous state can be used to improve the bioavailability of poorly soluble small molecule drugs. The disadvantage of the amorphous state is that it is commonly less physically (and chemically) stable than the crystalline counterpart, so the solubility advantage can be lost on the shelf before you get the formulation and drug in vivo. A means of addressing this stability problem is addition of a designed second entity to the API glass to stabilise it, be that with the addition of a single component or a mixture of excipients.

Co-amorphous materials are characterised by utilising at least two small molecule compounds homogenised in a single phase blend which presents as a glass. They utilise the intermolecular interactions for stability, akin to those that can be seen in small molecule crystalline materials. These interactions and mechanisms of how to determine them will be the subject of this talk. This talk will also highlight the potential similarities in approach of screening co-crystals and co-amorphous materials using the bicalutamide and ROY systems as examples.

David Berry
Lecturer in Pharmaceutics
Durham University

Case Study
Technology & Innovation
Formulating for Microneedle Delivery

Image result for queen's university belfast

Exploring the mechanisms available, including hollow, solid, dissolving and hydrogel-forming microneedles
Assessing the delivery of therapeutically relevant concentrations of drugs
Formulating to increase optimisation of Microneedle delivery
Bridging drug design with drug delivery science to create a larger pool of suitable entities for transdermal delivery

In addition to reviewing traditional microneedle technologies, this presentation describes production of unique microneedle arrays prepared from crosslinked poly(methylvinylether-co-maleic acid) which contain no drug themselves. Instead, they rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilised, resist hole closure while in place and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while modulated delivery and the potential for minimally-invasive extraction of skin interstitial fluid for monitoring purposes are also unique features. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of type of drug deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.

Prof. Ryan Donnelly
Chair in Pharmaceutical Technology
Queen’s University Belfast

Case Study
Biologics – Optimising Drug Formulations
Long-lasting Parenteral Formulations for Peptides
150px-Sanofi.svg
• Half-life extension approaches
• Prodrug depots with cleavable linkers
• Encapsulation approaches
• Devices One way to improve patient compliance consists in reducing the number of injections defined in the therapeutic plan.In the past years, sales for GLP-1 receptor agonists showed a clear trend towards weekly dosed drugs. This presentation will highlight different approaches and technologies used in developing long-lasting peptide formulations. Additionally, the device strategy and its impact on the peptide formulation will be also discussed at the end of the presentation.

Elisa Agostini
Head of Laboratory
Sanofi

17:05-17:10
Please move to your next session

17:10-17:45
Case Study
Small Molecules
Manufacturing and Analysis of Coated Amorphous Solid Dispersions and Nanocrystals by Electrospraying

leuven
• Amorphous solid dispersions
• Nanocrystals
• Electrospraying
• 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

Case Study
Technology & Innovation
Drug-Coated Microneedle Patch for Acute Treatments

Image result for zosano pharma

  • Drug- Coated Microneedle Patch Delivery System provides
    • Rapid delivery and pulsatile PK profile for improved efficacy
    • Room temperature stable formulations
    • Patient friendly alternative to injection
  • Application to peptide hormone (PTH 1-34) provides better anabolic effect than SC injection
  • Easy to use and rapid glucagon delivery for treatment of hypoglycemia may be a significant advantage

Mahmoud Ameri
‎Senior Director Pharmaceutical Development
Zosano Pharma

Case Study
Biologics – Optimising Drug Formulations
Development of Multidose Product – The Challenge of Preservatives

Image result for ferring Parenteral delivery is the second most applied route of drug administration and a steady increase in the number of parenterals has led to rise in demand for various drug delivery systems that ensure ease of administration as well as cost containment. Multidose delivery of parenterals, e.g. by use of an injection pen, are desired when repeated dosing is requires as it offers convenient administration as well as a cost effective product. With few exceptions, multidose parenterals incorporates a chemical preservative. Including a preservatives can introduce additional challenges in the drug development, in particular:

• Preservatives frequently show incompatibilities with other excipients like surfactants, buffers and stabilisers
• The preservation efficacy test results are heavily influenced by other excipients in the formulation
• The most frequently used preservatives for parenterals all displays tendencies to degrade over storage which may results in unwanted colouration of the product or loss of preservative efficacy.
• The stability of proteins may be negatively affected by presence of preservatives Ways to investigate and prevent the above challenges are discussed.

Dr. Helen Sjögren
Principal Scientist, Global Pharmaceutical R&D;
Ferring Pharmaceuticals A/S

17:45-17:50
Please move to your next session

17:50-18:25
Panel Discussion
Small Molecules
PANEL DISCUSSION Microneedles: Applications, advances and clinical translation
      Why are no true microneedle products on the market – discussion around manufacture, regulatory issue around repeated microneedle application and acceptance by patients and prescribers
      Intradermal administration vs. subcutaneous administration
      Dissolvable microneedles production vs. standard sterile formulation in syringe for subcutaneous administration
      Difference between transdermal vs ocular microneedle application?
      Challenges that microneedles face for ocular applications and patient compliance in microneedles application to the eye?
      Is microneedles the only way to get things through the skin? Is nanotechnology offering some perspectives
      A need for non-invasive sensoring – do microneedles have something to offer there?

Panel Members

Prof. Ryan Donnelly
Chair in Pharmaceutical Technology
Queen’s University Belfast (Panel Chair)

Brigitte Illel
Skin Delivery Platform Leader
Sanofi R&D France

Prof. Claus-Michael Lehr
Head of Department Drug Delivery
Helmholtz Institute for Pharmaceutical Research (HIPS)

Dr Thakur Raj Singh
Lecturer in Pharmaceutics
Queen’s University Belfast

Dennis Douroumis Professor in Pharmaceutical Technology and Process Engineering at University of Greenwich
University of Greenwich
United Kingdom

Keynote
Technology & Innovation
Bioprocess Development: New Advances in Drug Product Process Development & Validation
norvatis
  • Recent Advances in Bioprocess Development & Manufacturing
  • Approaches in developing drug product
  • Incorporating new tools into Drug Product development
  • Integrated bioprocess development for the future

Thanks to a combination of emerging technologies such as high producer cell lines, of single use disposable technologies and to continuous bioprocess, most of bioprocess bottlenecks have been overcome. Development of a biological drug product meanwhile is still mainly an empirical stepwise approach. It starts by a broad preformulation screening of different parameters such as buffering system, pH, isotonic agents and further stabilisers (detergents, amino acids, etc). Following the prescreening, an optimization step is run to preselect candidates to put on technical stability under intended storage conditions as well as under thermal stress.
While such development is seen as a well-established approach in developing biological drug products, it is however time and resources consuming, often putting drug product in the critical path.
New alternatives, based on prior knowledge gathered over the last 20 years in developing recombinant proteins and peptides, are emerging. Indeed taking advantage on a better understanding of the degradation pathways and on critical parameters, several simulation models have been developed. The models to determine the effects from thermal stress experiments and the downscale simulation tools are becoming very promising in predicting shelf-life and therefore accelerating biotherapeutics development. Integrated drug product development approach will be presented and discussed.

Otmane Boussif
Global Head Drug Product Development, BTDM-BPD
Novartis

18:30-20:00
Evening Reception

Day 3 – Wednesday 29th March 2017
08:00-08:20
Registration & light refreshments

08:30-09:05
Case Study
Small Molecules
The past, the Present and the Future of Alternate Route Drug Delivery – A Large Pharma Perspective

Image result for merck sharp and dohme

  • Traditional large pharma companies have been focused on the development of oral dosage forms for decades, and alternate route drug delivery has often played a complementary role in product life cycle management (LCM)
  • The combination of an increased need for patient compliance and the shift of portfolio from small molecules to biopharmaceuticals have presented enormous opportunities for novel drug delivery systems
  • Rapid internal proof-of-concept studies and partnership with external delivery technology companies offer an efficient approach for identifying the optimal delivery systems for the molecules of interests
  • Drug delivery mindset should be embedded across drug discovery to drug development and product LCM

Dr. Yunhui (Henry) Wu
Director of Biopharmaceutics in Pharmaceutical Sciences & Clinical Supply
MSD

Case Study
Biologics – Innovation in Drug Delivery
Use of Peptide and Protein Vectors to Cross the BBB for the Delivery of Therapeutic Concentration of Biologics

Image result for bioasis technologies inc

  • How do essential nutrients cross physiologically the Blood-Brain Barrier?
  • How to develop new vectors to cross the Blood-Brain Barrier?
  • Delivery of therapeutic concentration of biologics to the CNS
  • Best approach to deliver therapeutics to brain cells

Different approaches to cross the BBB and to delivery therapeutics to the CNS will be presented and discussed with the main emphasis being the platform developed by biOasis based on MTf and MTfpep. The efficacy of MTf chemically conjugated to Trastuzumab for the treatment of brain metastases in a mice model will be discussed. The lead peptide has shown very efficient and rapid transport across the BBB and was able to increase significantly the delivery of an antibody to the CNS after its chemical incorporation or expressed in a fusion protein. The peptide when expressed with the antibody as a fusion protein showed high transport rate in the brain. PK and PD study determined a very high transport rate of the antibody-MTfpep in the brain and a half-life comparable to mAbs. The application of this new peptide vector to oligonucleotides such as siRNA and on-going studies addressing the brain delivery of I2S for the treatment of Hunter Syndrome in k/o mice will be discussed. These studies will provide the proof of concept that Transcend both full length MTf and its derived peptides, can be used as carriers capable of shuttling a variety of compounds ranging from small anti-cancer agent to larger biologics across the BBB into the brain parenchyma in therapeutic doses that enable treatment of neurological disorders.

Dr. Reinhard Gabathuler
Chief Scientist
biOasis Technologies Inc

Case Study
Technology & Innovation

Physico Chemical Characterisation of Polymer-Drug Complexes

Synthon.logo4web

    • Polymer-drug complexes have been extensively used for several decades to enhance solubility of the active substances or simply stabilise its amorphous state.
    • The complexation process requires mixing at molecular level to promote effective polymer-drug specific interactions. Electrostatic and van der Waals forces as well as hydrogen bond may frequently participate in the formation of the complexes.
    • Spray-drying, hot melt extrusion, supercritical fluids processing or co-precipitation are techniques commonly used to generate stable polymer-drug complexes.
    • Efficiency and extent of hydrogen bonding can be investigated by means of calorimetric and spectroscopic techniques.
    • Qualitative and quantitative analysis of the interactions involved in the formation of a polymer-drug complex can help with the selection of the manufacturing process and to predict long term stability of the final formulation.

Solid solutions, also known as solid or molecular dispersions, have been used in pharmaceutical formulations for many years as a way of stabilising the amorphous state of drug substances, which are otherwise crystalline. This strategy can substantially enhance the solubility of some drug substances, which sometimes results into higher bioavailability. Moreover, the amorphous state can be also very useful to develop non-infringing generic formulations. Water soluble polymers are known to form complexes with small molecules in solution. The polymers can interact with drug molecules via electrostatic interactions (i.e. ion-ion, ion-dipole and dipole-dipole) but other types of forces, such as van der Waals and hydrogen bond, may frequently participate in the formation of the complex. The complexation process requires mixing at molecular level (i.e. solution or melt) in order to establish effective polymer-drug specific interactions. A varied number of instrumental techniques can be used to characterise and quantify the interactions between polymer and drug substance; spectrophotometric and calorimetric analyses are amongst the most popular. Understanding of the physico-chemical properties of the solids solutions offers a molecular insight into the properties of the final dosage form.

Jose Velada
Chief Scientific Officer
Synthon
Netherlands

09:05-09:10
Please move to your next session
Session chairs
Small Molecules – Dr. Paulina Paszkiewicz, Nanologica AB
Biologics – Patrick Garidel, Director Pharma Development, Biopharma Boehringer Ingelheim Germany
Technology & Innovation – Olaf Queckenberg, Head of Global Chemical & Pharmaceutical Development Bayer Pharmaceuticals Division Germany
09:10-09:45
Technology Spotlight
Small Molecules
 Smoothening the Development Path from Early Development through Commercialization when Working with a CDMO

patheonThe pharmaceutical development of a product can be a bumpy road, with many challenges arising along the way that pose a risk to timelines, cost and even clinical success. With as many as 68% of development programs failing in Phase II, balancing the amount of effort invested in early development in order to prevent financial risks and delays from occurring in late stage development is a complex but important exercise for today’s pharmaceutical organizations. With more and more development projects being managed by emerging pharmas and outsourced to CDMOs, this complexity only seems to be increasing.

During the presentation, we will evaluate how integrated pharmaceutical development teams can partner with CDMOs to address the challenges they face. In order to simplify development and speed successfully to late stage development and commercialization, pharmaceutical executives must consider and be prepared to address some of these critical areas during early stage development to mitigate risks and make sure they are prepared to advance to Phase IIb/III trials.

  • Manufacturing process design scale-up
  • Biopharmaceutics
  • Risk- and science-based approaches

Kasper van den Dries, MSc, PhD
Senior Director and Principal Scientist, Solid Dose Development, Europe
Patheon

Technology Spotlight
Biologics – Optimising Drug Formulations
Getting the Full Picture: Predicting Protein Stability Using Chemical and Thermal Denaturation

nano-temper

  • How to make better informed decisions earlier in the biopharmaceutical development workflow
  • Explore the modern alternative to DSC: 100x faster, 40x less sample
  • Learn how to significantly reduce time-to-market for your new biopharmaceuticals

Dr. Anna Münch
Senior Application Specialist
Nano-Temper Technologies

Technology Spotlight
Technology & Innovation

Maltitol and Protein Stabilization: Evaluation and Development of a New Excipient for Pharmaceutical Applications

Roquette

    Carbohydrates are widely used for the stabilization of proteins in medical and veterinary applications. Development of new excipients for injectable is challenged by the increasing demand for safer products with improved efficiency and reduced side effects. Control of potential contaminants is a rising concern in naturally-derived carbohydrates. Chemical inertness is also a key requirement for formulation stability and in-vivo biocompatibility upon injection (e. g. glycation end-products). In this study, protein stabilization was investigated on a selection of carbohydrates in a temperature shock study in solution with proteins selected from low to medium molecular weights. The presentation will review the example of maltitol and highlight the differences and the superior performances of maltitol for its application in pharmaceutical formulations.

Denis Simon
Director of Technical Service, Pharmaceuticals
Roquette

09:45-09:50
Please move to your next session

09:50-10:25
Case Study
Small Molecules
Polymeric Micelles for Targeted Drug Delivery

In our Department thermosensitive and biodegradable polymeric micelles based on poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate] (mPEG-b pHPMAmLac) have been developed for passive and active drug targeting. Their small size (60-80 nm) and hydrophilic corona result in enhanced blood circulation and tumor accumulation exploiting the enhanced permeation and retention (EPR) effect. Doxorubicin was covalently linked to the core of these micelles through a hydrolytically sensitive hydrazone spacer and an increased in vitro and in vivo efficacy was observed. In a follow up study, we conjugated an anti-epidermal growth factor receptor (anti-EGFR) nanobody as a targeting ligand to the micellar surface. It was demonstrated that the coupling of the nanobody on the surface of the micelles resulted in increased in vitro cytostatic activity (14C cells), and also significantly enhanced the antitumor activity and survival of 14C tumor-bearing mice in vivo. In another study, polymerizable and hydrolytically cleavable dexamethasone (DEX) derivatives were covalently entrapped in core‐crosslinked polymeric micelles in order to achieve highly effective glucocorticoid targeting for rheumatoid arthritis (RA) therapy. By varying the oxidation degree of the thioether in the drug linker, the hydrolysis rate – and therefore the release kinetics of DEX – could be tightly controlled, with half‐lives ranging from 10 to 170 days. Upon a single i.v. injection of the most rapidly releasing DEXmicelles, highly efficient disease treatment was achieved in two different animal models of inflammatory arthritis, with clinical signs of arthritis returning to levels observed for healthy controls. In a recent approach we developed polymeric micelles with aromatic benzyl groups in the core which had a high loading for the anticancer drug paclitaxel. Moreover these drug loaded micelles had excellent stability in the circulation and showed very good antitumor activity in different mice models.

Prof. Wim Hennink
Head of Pharmaceutics Department
Utrecht University, The Netherlands

Case Study
Biologics – Optimising Drug Formulations
On Development of a Long Acting Injection of an Antidiabetic Peptide
Sun-Pharma
• Assessing market dynamics of a antidiabetic peptide
• Key differentiators affecting upcoming market
• Role of drug delivery systems
• Long acting injections: how long is good enough?
• Challenges, Proof of concept and discussionDatamonitor Healthcare expects the antidiabetic peptide class to be worth in 2 digit billions across the US, Japan, and the five major EU markets as we move to the next decade. Thus, the differentiators in terms of potency, activity, indications, ease of use, combinations, technology-from oral to ultra-long acting injections may all find their place in market. The challenge though would be pricing erosion and ability to charge premium given the clinical requirement is significant for such product. Therefore, the complexity of manufacturing technology and ability to provide cheaper better and faster (CHE-BE-FA) would be critical. This presentation will discuss a technological strategy keeping user at the core and the supplier surrounding it to develop and establish a proof of concept on a long acting GLP-1 agonist.

Ajay J. Khopade
Vice President-R&D, Formulation Development (Non-Orals)
Sun Pharma Advanced Research Co. Ltd.

Case Study
Technology & Innovation
Pharmaceutical and Biomedical 3D Printing Applications
University of Greenwich - logo

• Coupling Hot Melt Extrusion and 3D printing
• 3D printing of “candy like” paediatric dosage forms
• Miniature 3D printing of cardiovascular stents
• 3D printed dissolvable microneedles

3D printing has attractive significant interest in pharmaceutical and biomedical applications. By using various 3D printing technologies, it is feasible to process a wide range of printing materials for drug delivery purposes. 3D printing can be easily coupled with extrusion processing to develop palatable paediatric formulations of water insoluble drugs. More advance applications involve the development of implantable coronary stents for the delivery of antiproliferative and antipletelt drugs for dual release. Another 3D printing application is the development of polymeric transdermal microneedles of various designs that dissolve rapidly after piercing the skin to deliver active materials (e.g. vaccines, macromolecules).

Dennis Douroumis Professor in Pharmaceutical Technology and Process Engineering at University of Greenwich
University of Greenwich
United Kingdom

10:25-11:15
Delegate-to-Delegate Meetings & Refreshment Break

11:15-11:50
Case Study
Technology & Innovation
Challenges in the Analysis of Spray Dried Dispersion Formulations: Dissolution
Image result for bristol myers squibb

• We will illustrate some of the unique technical challenges presented by SDDs in terms of method development compared to traditional formulations.
• We will review some of the tools for building mechanistic understanding
• We will discuss the role of media properties e.g. the impact of surfactant selection on dissolution method development.

This presentation draws attention to some of the unique technical challenges presented by Spray Dried Dispersions, in terms of in-vitro dissolution method development, compared to traditional formulations. The importance of building a sound understanding of the mechanistic processes involved in the dissolution is explored along with the relative roles played by both the polymer and the API in question. Practical examples are given of some of the tools that can be used to help build a comprehensive insight into the mechanism(s), with a view to identifying critical formulation properties. Some case studies are presented which highlight the importance of the role of the dissolution media selection on the rate and plateau value of the dissolution profile obtained.

Adele Patterson Senior Research Investigator
Bristol-Myers Squibb
United Kingdom

Case Study
Biologics – Optimising Drug Formulations
Recent Trends in the Similarity Assessment of Biosimilars
Related image
    • Structural and functional data are the foundation of the similarity assessment of Biosimilars
    • Regulatory agencies require different similarity assessment approaches
    • FDA currently requires equivalence testing for those parameter with the highest clinical relevance and direct link to mode of action
    • The impact of this FDA requirement on biosimilar development and approval will be discussed

The detailed characterization of the originator product as well as identification and understanding of structure/function relationship of variants are the basis for definition of the development target for biosimilars. Progress in analytical sciences and more and more powerful analytical technologies allow describing the reference products as well as the corresponding biosimilars in every detail covering multiple quality attributes. The generated wealth of analytical data offers opportunities and challenges and therefore have to be evaluated systematically.
The comprehensive set of quality attributes are ranked according to their impact on PK, safety and efficacy and uncertainty in the critical quality attributes (CQA) assessment. The determined criticality scores guide biosimilar technical development, definition of the control strategy and play an important role in the definition of the strategy for the final similarity assessment in the context of the totality of evidence concept. Statistical data evaluations are recently suggested to support the similarity evaluation. Statistical methodologies should provide tools to decide which parameters have to be discussed/investigated in more detail. However, statistics should not be a self-contained claim for biosimilarity on the quality level, it always should be just a contributor to the totality of evidence. Benefits and limitations of statistical approaches for similarity assessment will be discussed in this presentation, in addition to how the statistical results fit into the overall evaluation of biosimilarity.

Andreas Seidl
Head Global Analytical Characterization & Bioanalytics Sandoz/Hexal Germany

Case Study
Small Molecules
Development of Pediatric Products and Challenges from Clinical Trials to Registration

Image result for angelini
• The necessity and challenges of clinical research involving children: differences and peculiarity for the development of a paediatric drug;
• The health authority position;
• The off label use: the size of the problem;
• To invest in paediatric population should be highly rewarded;
• The right formulation for the right population: a good challenge and a big opportunity.

In the field of the paediatric product development, there are several ethical and practical issues. However, we all know very well that children need dedicated clinical programs. The research should be supported and encouraged in order to limit the extended off label use of drugs that have been approved for adults. In this talk, we will go through the challenges and the opportunities that the paediatric products may offer to a research organization.

Serena Tongiani, Ph.D
Chief Scientific Officer, R&D; Director
Angelini Acraf S.p.A

11:50-11:55
Please move to your next session

11:55-12:30
Technology Spotlight
Small Molecules
Repurposing of Marketed Drugs for Treating Infectious Disease: How Drug Delivery Technologies Bring Medical Benefit to Patients

nanologica

  • Nanologica’s nanoporous silica technology is a versatile drug delivery platform that addresses formulation challenges for improved clinical benefit
  • Key applications of NLAB SilicaTM are enhancing bioavailability, overcoming pH-dependent solubility issues and improving PK variability
  • Two case studies of reformulating anti-infectives with NLAB SilicaTM will illustrate how a Drug Delivery technology can be used for repurposing of marketed drugs
  • How value can be maximised by the right collaboration models between technology partner and pharma company

Adam Feiler
Chief Technical Officer
Nanologica

Technology Spotlight
Technology & Innovation
iCRT – Advanced Drug Delivery Platform
Tackling your formulation and delivery challenges
LUCIDEON
This presentation will introduce Lucideon’s proprietary technology platform iCRT and our latest research and development for the pharmaceutical industry. The iCRT platform is highly versatile and can tackle formulation and delivery challenges including abuse of pharmaceutical drugs.
iCRT-deter is our key technology for abuse-deterrent formulations (ADF). iCRT-deter offers a robust solution for the abuse deterrence market, averting both crushing, intravenous abuse and manipulation via solvent extraction.
The iCRT platform also tackles:
  • Formulation instability – for biologics and small molecules
  • Poor bioavailability – enhancing solubility and stability
  • Unfavourable release profiles – IR and ER options

Aia Malik
Product Manager, Healthcare
Lucideon

Technology Spotlight
Technology & Innovation
New Opportunities for Patient Centric Formulations

adareThis presentation provides an overview of the company’s unique capabilities, while showcasing its broad range of proprietary technologies and successful patient-centric formulations.

  • • The challenge of therapeutic principles for certain patient populations, such as pediatric, geriatric and dysphagic patients, adolescents and patients with neurological disorders will be addressed.
  • • Illustrate the versatility of drug delivery solutions in the field of oral dosage forms to meet the needs of patients, thereby encouraging adherence while supporting optimal disease management and ultimately providing opportunities for improved outcomes.
  • • Case studies will be featured ̶̶—demonstrating novel/improved proprietary formulation technologies for oral delivery ̶̶—core competencies of Adare Pharmaceuticals.

Holger Neecke, PhD, MBA
Director, Business Development
Adare Pharmaceuticals

Luigi Boltri, Msc.
R&D Director, Innovation & Technology Liaison
Adare Pharmaceuticals

12:30-12:35
Please move to your next session

12:35-13:10
Case Study
Small Molecules
Spatio-Temporal Drug Delivery: Delivering on the Unmet Medical Need
Image result for merck sharp and dohme
• A general introduction to unmet medical needs in multiple therapeutic areas such as bacterial/viral infections, oncology, cardiometabolic, and ocular will be provided • The value proposition of spatio-temporal drug delivery, in light of the unmet medical needs and emerging pipeline, will be established • Various spatio-temporal drug delivery approaches such as sustained release, targeted delivery and localized delivery will be explained and exemplified • Opportunities and Challenges with discussed drug delivery technologies will be highlighted as future directions

Sachin Mittal
Senior Principal Scientist
Merck Sharp & Dohme

Case Study
Biologics – Optimising Drug Formulations
Selecting for Success – A Rational CMC Approach to the Early Assessment of Lead Candidate Molecules
amgen
  • The QbD Mindset as basis for a rational Molecule Assessment
  • The “moving target” – challenges related to an early TPP
  • The importance of an end-to-end process perspective
  • The Molecule Assessment process – design and execution
  • The decision making process

Cornelius Pompe
Head of Formulation Development
Amgen Research (Munich) GmbH

Case Study
Small Molecules
Formulating ‘tastier’ medicines for children

Image result for UCL

    • What the Patients think
    • What Regulator wants
    • What Industry does
    • what Academia researches

A range of dosage form specific factors, including undesirable organoleptic or physical properties, can be linked especially in children to intentional or unintentional non-adherence with the heightened likelihood of suboptimal therapy. Indeed spitting, vomiting or refusing to take a medicine is self-limiting. Yet in paediatric medicines marketing-authorisation applications, demonstrating that ‘users’ are able and willing to use the medicinal product as ‘intended’ without the need for coping mechanism is a key binding element of paediatric investigation plans (PIP). This needs to be addressed during clinical trials if not leveraged before, despite no standard methodology or clear acceptability criteria. Alternatively, effect of co-administration with food/beverages to improve acceptability/palatability need to be studied suffering from a similar lack of guidance on how to do so. As the EU paediatric regulation celebrates its 10 year anniversary, data emerging from PIPs are still scarce to form guidance. This is problematic both for regulators and industry which has led to pre-competitive collaboration such as the SPaeDD-UK project (Smart Paediatric Drug Development-UK; www.paediatricscienceuk.com). Industrial and academic expertise has led to increased fundamental understanding and so the potential to develop tools to predict quality and performance of paediatric formulated products, establishing an industry standard framework while ensuring regulatory compliance.

Dr Catherine Tuleu
Reader in Pharmaceutics (Paediatric Drug Delivery)
UCL School of Pharmacy

13:10-14:10
Networking Lunch
 Lunch

14:10-14:45
Panel Discussion
Small Molecules
PANEL DISCUSSION PART I
Improving Safety and Effectiveness – The Role of Patient Centric Drug Product Development

Patient centricity has become a buzz word in the past years being used in several different contexts. A definition for “Patient centric pharmaceutical drug product design” was recently suggested and raised the importants the patient factors and patient-product interface with regard to effectiveness and drug safety. For the pediatric patient population guidelines have been put in place resulting in increasing scientific research about this patient population. With the increasing life expectancy and multimorbidity additional important patient populations with specific needs beyond the clinical aspects are arising that will come into the regulatory and scientific focus in the coming years. This workshop will discuss how to identify and understand patient needs/characteristics and why pharmaceutical product design is so important in order to meet this patient needs. In addition to this, approaches towards patient centric drug product design will be addressed in the workshop and panel discussion.

    Panel Members

Prof. Dr. Sven Stegemann
Patient Centric Drug Product Design and Manufacturing Leader
Graz University of Technology (Panel Chair)
Austria

Dr. Mansoor Khan
Vice Dean
Texas A&M Health Science Center, University of Texas (Former Director, Division of Product Quality Research, FDA)

Dr Catherine Tuleu
Reader in Pharmaceutics (Paediatric Drug Delivery)
UCL School of Pharmacy

Serena Tongiani, Ph.D
Chief Scientific Officer, R&D; Director
Angelini Acraf S.p.A

Luigi Boltri, Esq.
R&D Director, Innovation & Technology Liaison
Adare Pharmaceuticals

Case Study
Biologics – Innovation in Drug Delivery
Multi-Compartmental Oral Delivery Systems for Silencing Intestinal Tissue Transglutaminase-2 and Interleukin-15 Genes in the Treatment of Celiac Disease

Image result for alnylam pharmaceuticals Nanoparticles in Microsphere System (NiMOS) was developed for overcoming oral barriers to siRNA delivery

  • Small Interference Ribonucleic Acid (siRNA) molecules were encapsulated within gelatin nanoparticles
  • siRNA containing gelatin nanoparticles were encapsulated within poly-ε(caprolactone) microparticle to form NiMOS
  • Gelatin nanoparticles showed efficient cellular uptake, RISC loading and target gene silencing, when tested in vitro
  • NiMOS showed efficient target gene silencing in the small intestine
  • Knockdown of IL-15 expression in a poly(I:C) based mouse model of celiac disease resulted in:
    • Decrease in expression of proinflammatory cytokines
    • Reduced MPO activity
    • Reduced body weight loss
    • Reversal of histopathological changes with signs of tissue regeneration

Husain Attarwala
Senior Associate Scientist
Alnylam Pharmaceuticals

Case Study
Small Molecules

Advanced Characterisation of Pharmaceutical Formulations
UoKEurope
  • Pharmaceutical Formulations (e.g. tablets, extruded materials, nano and micro particles)
  • TOF-SIMS Characterization and Imaging
  • AFM for Pharmaceutical Applications
  • Micro-CT analysis of extruded formulations
  • Raman imaging analysis of pharmaceutical tablets

Structure-property relationships are often poorly defined in advanced continuous pharmaceutical manufacturing processes and products and hence it is difficult to control final product performance to the required degree to deliver advanced functionality. The dynamics of particles within complex mixtures and the effect of processes and storage on their disposition and microstructure is also challenging to measure. Hence, there is a clear need to have techniques for analysis and measurement of composition, dynamics and structure with increased spatial and temporal resolutions. Therefore, the measurement of surface composition and microstructure of pharmaceutical particles and formulated systems informing structure-property relationships is crucial. This seminar will evaluate and discuss the capability of Metrology (e.g. ToF-SIMS, AFM, and Raman Microscopy) analysing a variety of Pharmaceutical products (e.g. electrospun scaffolds, extrudates, tablets).

Dr Dimitrios A. Lamprou Associate Professor In Pharmaceutics / Drug Delivery
University of Kent
United Kingdom

14:45-14:50
Please move to your next session

14:50 – 15:25
Panel Discussion
Small Molecules
PANEL DISCUSSION PART II
Improving Safety and Effectiveness – The Role of Patient Centric Drug Product Development

Patient centricity has become a buzz word in the past years being used in several different contexts. A definition for “Patient centric pharmaceutical drug product design” was recently suggested and raised the importants the patient factors and patient-product interface with regard to effectiveness and drug safety. For the pediatric patient population guidelines have been put in place resulting in increasing scientific research about this patient population. With the increasing life expectancy and multimorbidity additional important patient populations with specific needs beyond the clinical aspects are arising that will come into the regulatory and scientific focus in the coming years. This workshop will discuss how to identify and understand patient needs/characteristics and why pharmaceutical product design is so important in order to meet this patient needs. In addition to this, approaches towards patient centric drug product design will be addressed in the workshop and panel discussion.

    Panel Members

Prof. Dr. Sven Stegemann
Patient Centric Drug Product Design and Manufacturing Leader
Graz University of Technology (Panel Chair)
Austria

Dr. Mansoor Khan
Vice Dean
Texas A&M Health Science Center, University of Texas (Former Director, Division of Product Quality Research, FDA)

Dr Catherine Tuleu
Reader in Pharmaceutics (Paediatric Drug Delivery)
UCL School of Pharmacy

Serena Tongiani, Ph.D
Chief Scientific Officer, R&D; Director
Angelini Acraf S.p.A

Luigi Boltri, Esq.
R&D Director, Innovation & Technology Liaison
Adare Pharmaceuticals

Case Study
Technology & Innovation
Current Procedures to support Development of Innovative and Novel Drugs
MHRA

• An introduction to the MHRA innovation office, examples of the typical queries we receive, case studies of how we can help, how to access this service.

• Overview of the MHRA scientific advice options available; product specific, broader scope and parallel advice with NICE.

• An introduction to the MHRA early access to medicines scheme, the 2 step evaluation process and a case example of a novel treatment that received a positive opinion.

The MHRA has a number of procedures available to support development of innovative and novel drugs that can help organisations of all backgrounds and sizes. In this talk the focus will be on the MHRA innovation office, the types of MHRA scientific advice available and the UK early access to medicines scheme, including several case examples and how to access advice.

Dr Andrea Wallington Medical Assessor
Medicines and Healthcare products Regulatory Agency
United Kingdom

Case Study
Small Molecules
Pro-active Pharmacovigiliance from Early Development to Life Cycle Management of Medicinal Products

• Changing paradigm: From data gathering to strategic planning
• How to move from reactive to proactive safety surveillance
• Experience with Regulators in terms of signal & benefit risk management

Merck logo correct

Heike Schoepper, MD, PhD, MBA
Head of Global Drug Safety Biopharma | Research & Development | Global Medical Affairs and Global Drug Safety
Merck KGaA
Germany

15:25-15:30
Please move to your next session

15:30 – 16:05
Case Study
Small Molecules
Pharmacovigilance and Quality Control – Two Key Pillars of Risk Minimisation for Patients

Merck logo correct

• The close relationship between Quality and Safety

• Examples of risks and their mitigation, including medication errors

Heike Schoepper, MD, PhD, MBA
Head of Global Drug Safety Biopharma | Research & Development | Global Medical Affairs and Global Drug Safety
Merck KGaA
Germany

Case Study
Biologics – Optimising Drug Formulations
Scale Down models for Robust Biologics Drug Product Development

Image result for bristol myers squibb

        The approach for Scale Down models for Biologics Drug Product Development can be split into two main categories:

      • Experiments with small Scale version of the large scale unit operations with use of proper scaling parameters
      • Mini-piloting tools develop to mimic the worst case scenarios for various unit processes of drug product manufacturing – risk assessment tools to provide guidance on candidate selection, formulation selection as well as process parameter design space selection

The prominent stresses that the protein molecules see during the drug product manufacturing are interfacial stress, shear stress and cavitation. The mini-piloting tools developed here are to mimic these stresses at different levels to understand the susceptibility of the molecules to them and their impact on critical quality attributes.

Smeet Deshmukh
Sr. Research Investigator, Biologics Formulation Development Bristol Myers Squibb USA

16:00-16:35