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  • Biologics
  • Innovation
  • Small Molecules
Day 1 – August, 28 2017 – Monday
7:30-8:25AM
Registration & Refreshments

8:25-8:35AM
Chair’s Opening Remarks

8:35-9:10AM
Plenary
Improving Patient Convenience: Challenges from the Formulation Front
sano2
    • Patient centered integrated device implementation in early development
    • Role of developability and pre-formulation development
    • Analytical tools and workflows to assess device ability potential of therapeutic proteins.

Formulation development for biologics is constantly changing to reflect the emerging of new antibody scaffolds, the increasing use of subcutaneous injection and the growing constraints on development timelines particularly at the early clinical stages. The growth of self-injectable combination products has necessitated the holistic evaluation of several components at the same time in a fully integrated approach. The interactions between each component collectively drive the final product performance and quality in the hands of the patient. Multiple variables could interact between each other and then affect key quality attributes of the final product. The role of developability and deviceability to minimize the unexpected is critical as well as the use of proper workflows and analytical methods. Drug Device integrated development through a patient-centric Integrated System Design approach is a strategic imperative. This talk will present a summary of current challenges and opportunities for effective development of robust drug products.

Bernardo Perez-Ramírez, MSc, Ph.D.
Senior Scientific Director, Global Pharmaceutical Development-Biologics
Sanofi

9:15-9:50AM
Case Study
Biologicals
High Throughput Screening of a monoclonal antibody. Practical Considerations.
gsk
    • Study Design and Constraints
    • Material Quality
    • mAb Stability as a lyophile: A case study

Cycle time reduction to achieve faster throughput of medicines development can be achieved with strategies that include high throughput formulation screening. Innovative approaches using high throughput screens often have practical considerations and limitations that must be understood to achieve sound formulation selection decisions. Whilst some of these are similar to conventional formulation development considerations, additional concerns when using 96 well plate based formats must be taken into consideration during sample preparation, stability storage conditions, analytical testing and the statistical designs that underpin these studies. This presentation will cover some of the concerns and mitigating approaches to high throughput approaches using robotic liquid handlers, will describe a case study of a high throughput formulation approach for a mAb and will discuss some of the trade-offs made during final formulation selection decision.

Myrna Monck
Director Biopharm Technologies
GSK

Case Study
Small Molecules
Molecular Dynamics Simulations of Amorphous Systems

UK

    • MD simulations reveal molecular interactions that may facilitate interpretation of experimental data
    • Energy calculations enable estimates of amorphous miscibility
    • Water uptake and the influence of water on drug-excipient interactions can be explored
    • Water clustering leads to domains having enhanced mobility

Molecular dynamics (MD) computer simulations have shown promise in predicting various properties of amorphous excipients, amorphous drugs, and amorphous drug formulations. Structural, thermodynamic, and kinetic features that can be compared to experimental observations are of particular interest. MD simulations enable molecular level exploration of underlying molecular interactions of the excipients themselves, drug-excipient interactions, and the influence of water uptake. Thermodynamic properties such as the Flory-Huggins interaction parameter can be determined in order to predict amorphous drug miscibility with amorphous excipients and the solubility or dissolution rate enhancement potentially attainable through the use of amorphous systems. Dynamic properties related to molecular mobility are also of interest. Insights obtained from studies of various systems including polymer excipients (PVP, PVA, PLA, HPMC, and HPMCAS), several model drugs including indomethacin, felodipine, and carbamazepine, and their amorphous formulations at varying water contents will serve as examples in this presentation.

Bradley D. Anderson
Professor, Department of Pharmaceutical Sciences
University of Kentucky

9:55-10:25AM
Solution Spotlight
Innovation
Beyond Aseptic Processing
revox Increased sophistication of drug delivery methods and greater scrutiny of microbiological assurance standards are on a collision course. Learn the standards and methods of yesterday and today and the trends that will impact the way you assure your products microbiological safety in the future.

Mason Schwartz
Director of R&D
REVOX

Solution Spotlight
Small Molecules
Nanoporous Silica Particles for Enhanced Drug Performance: Applications Beyond Increasing Solubility

nanologica 200

  • 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
10:25-11:20AM
Meetings
iSolve & Networking Refreshments

iSolve-logo

11:20-11:50AM
Case Study
Innovation
Optimizing Parenteral Delivery of Novel Class of Anticancer Drug Conjugates

tarveda

      • Pentarins are miniaturized drug conjugates that rapidly penetrate deep into solid tumors to drive efficacy
      • Pentarins can contain components with diverse physiochemical properties, such as amphiphilic conjugates, requiring careful formulation optimization for physical (solubility, aggregation/ Self-assembly)
      • Pentarins must be formulated with compatibile surfactants, complexing agents, and co-solvents
      • When there is a cleavable linker the Pentarin must have sufficient chemical stability (pH effect, temperature) in the formulation to enable in vivo testing
      • The high throughput optimization of Pentarins requires the in vivo evaluation of lead conjugates necessitating seamless interactions between medicinal chemistry, biology and formulation

Pentarins™ are miniaturized drug conjugates that possess complex molecular structure and provide rapid and deep penetration into solid tumors leading to improved efficacy. Tarveda’s lead Pentarin™, PEN-221 is currently in a Phase 1/2a clinical trial. PEN-221 is designed to treat patients with neuroendocrine cancers and small cell lung cancers that overexpress somatostatin receptor 2. Early-stage pharmaceutical pre-formulation is a critical component in the rapid development of stable, safe, and effective dosage forms for new therapeutic candidates. A synergistic approach to advance Tarveda’s Pentarin™ platform development, consisting of a strong discovery team with chemistry, biology and fit-for-purpose formulation development, enabled candidate selection. After drug candidate selection for early stage clinical trials, a more vigorous and scrutinizing formulation development assured the successful transition of PEN-221 into clinical studies.

Beata Sweryda-Krawiec
‎Research Leader
Tarveda Therapeutics

Case Study
Small Molecules
Is it crystal clear? Stability and performance prediction for amorphous pharmaceuticals

merck

  • Basic fundamentals of amorphous pharmaceutical stability predictions
  • Overcoming the limitations of RTD temperature sensors
  • Molecular mobility – considering the different molecular motions that exist in amorphous pharmaceuticals
  • Predicting the long-term physical stability of materials based on these molecular motions

Majority of new drug candidates under development are poorly water-soluble. The amorphous state is of considerable interest since it confers higher apparent solubility and faster dissolution than its crystalline counterpart. However, being the thermodynamically unstable form, it runs the risk of crystallization leading to the loss of solubility advantage. In this presentation, we will discuss different approaches to predict the solid-state and solution state physical stability of the amorphous state with case studies.

Sunny Bhardwaj
Sr. Scientist
Merck

11:55-12:30PM
Solution Spotlight
Innovation
Efficiency Through Excipient Design: Improving Oral Solid Dose Manufacturing Processes

dow

    Manufacturing in the pharmaceutical industry is ubiquitously faced with challenges for cost control, flexible operations and designing enabled dosage forms. While existing and emerging technologies have been employed in these specialized processes, current excipients limit their production capabilities and efficiency. Though process modification can improve production to an extent, it is insufficient alone. Through the alteration of excipient physical and chemical properties it is possible to utilize our solid dose manufacturing technologies to their fullest extent. In this presentation, tailored functional excipients optimized for specific manufacturing processes and their impact on process efficiencies will be discussed. This includes materials designed for direct compression tableting, dry powder coating, spray drying, and hot melt extrusion.

Kevin O’Donnell
‎Associate Research Scientist
Dow

Solution Spotlight
Small Molecules
Accelerated Formulation Development for Poorly Soluble Drugs and Modified Release Products

Quotient

      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

Dr Kevin Kane
‎Scientific Director (North America), Biopharmaceutics & Clinical Pharmacology
Quotient Clinical

12:35-1:05PM
Case Study
Biologicals
New Approaches to Advance Therapeutic Drug Delivery across the Blood-Brain Barrier to Brain and Brain Tumours
south-uni
      • Anticancer drug delivery to brain metastases of breast cancer is restricted by the blood-brain barrier.
      • Drug delivery is enhanced in leaky tumors, which account for a small fraction (8%) of brain metastases of breast cancer.
      • Only 5% intratumoral region of the leaky brain metastases receive drug concentrations similar to that of peripheral tumors.
    • Preclinical studies of angiopep – drug conjugates demonstrated enhanced drug delivery to brain tumors.

The blood-brain barrier restricts the brain delivery of most currently active anticancer agents used in the treatment of brain tumours. • The magnitude of this restriction is extremely large (50-200 fold) for some of the most commonly used agents cytotoxic agents (paclitaxel, doxorubicin, vinorelbine,) and newer molecularly-target agents. • In only a very small subset (<5%) of brain metastases is the barrier sufficiently compromised to allow marked drug accumulation. • This restriction was found in matching human brain metastases. • This drug delivery compromise can be overcome in brain metastases using several approaches, including drug agents which show poor affinity for barrier active efflux transport, enhanced barrier passive permeability, elevated active efflux, or molecularly targeting mechanism, such as those in using LRP, transferrin, insulin receptor, or other mechanisms.

Ramakrishna Samala
Assistant Professor
School of Pharmacy, South University Columbia

Case Study
Small Molecules
Integration of solid form selection and biopharmaceutical risk assessment into drug product design in the early phase development

phzer

    • Technical & Business Success Factors for Drug Delivery Programmes
    • Fighting the growing trend to outsource in an effort to maintain core skill sets
    • Minimizing initial investment to reduce risk and reduce costs later on
    • Integrating form with formulation in early development to maximise their values mutually
    • Developing a true understanding of both form and formulation for efficient development

Fundamental understandings of the biopharmaceutics, physicochemical and solid-state properties of the drug molecule are necessary to develop and progress a candidate compound from discovery to the clinics. These concepts and a toolbox of enabling pharmaceutical technologies will be explored. Strategies for form selection, formulation development, and biopharmaceutical risk assessment in different development stages will also be discussed.

Tao Zhang
Senior Scientist
Pfizer

1:05-2:05PM
Networking Lunch

Networking-Lunch-logo

Lunch & Learn Roundtable: Bioavailability Enhancement with SoluMatrix Fine Particle Technology™

iCeuticaLogo-2 (web version)

    • Barriers to oral bioavailability
    • Benefits of smaller crystalline particles
    • SoluMatrix Fine Particle Technology™
    • Case studies

Brian Jones
Business Development
iCeutica

2:05-2:40PM
Case Study
Biologicals
Drug Product Development and Drug Delivery

Biogen

      • Drug delivery decision, including device type can be influenced with different formulation approach
      • Formulation constraints should be evaluated early on
      • Setting up a Target Product Profile, however broad, at an early drug development stage is critical
      • Clinical trial / studies should be planned and designed to accommodate the variability and constraints of drug formulation and drug delivery
    • Drug delivery decision timing need to be made, with an eye on optimising organisation investment

Atul Patel
Director Devices & Packaging
Biogen

John Ruesch
Vice President Protein Formulation Development
Biogen

Case Study
Small Molecules
Analyzing the Potential Root Causes of PK Variability in Preclinical Species to Inform Derisking Strategies in Discovery and Early Development
merck
      • Variability in pharmacokinetics (PK variability) in preclinical species can lead to significant issues throughout drug development. It can cause failure to define dose-exposure relationship, or result in overlap in exposures between dose groups which can preclude establishing adequate safety margins. Overall, effects on programs can be significant and lead to increased resources, elongated timelines and/or termination.
      • It is therefore critical to act proactively to evaluate the risk of PK variability for any molecule transitioning to development.
      • A cross-functional effort was initiated to analyze historical datasets and identify the potential root causes of PK variability in preclinical species. The impact of route of administration, species, dose and physiological parameters was studied; and intrinsic properties of the compounds such as BCS class and solubility were correlated to heterogeneity in exposures.
    The presentation highlights criteria established for in vitro and in vivo risk assessment of PK variability as well as mitigation approaches.

Pierre Daublain
Principal Scientist
Merck

2:45-3:15PM
Solution Spotlight
Biologicals
Unleash Automated Buffer Exchange
unchained-labs • 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

Joe Barco
Sr. Director Marketing.
Unchained Labs

Solution Spotlight
Small Molecules
Oral Delivery of Live Bio-therapeutics: Drug product development for FIM studies

quay

      – 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
‎Manager, Pharmaceutical Development
Quay Pharma

3:20-3:50PM
Case Study
Innovation
Knowledge-Based Selection Strategies Using the QbD Approach to Ensure Syringe Selection Decisions Meet Technical and Business Requirements
gsk Presentation will contain comprehensive study results that evaluated available syringe products to identify the best fit for most biopharm requirements. The benefit is that a platform approach and second source not only ensures continuity of supply but also meets standardization for compliance advantage, minimizes process development and capital investment for new products and enables greater speed of decision making and implementation.

Aarti Gidh
‎Manager, BioPharmaceutical Product Sciences (BPS)
GSK

Case Study
Small Molecules
Advances in Spray Granulation Techniques

nova

  • The importance of process parameters on in vitro and in vivo behaviour of dried nanosuspensions in spray granulation
  • Evaluating the effects of spray mode, spray rate and atomizing pressure for spray granulation of drug nanosuspensions
  • Use of fluid bed granulation for drying of pharmaceutical particulates on micron-sized granule substrates explores

Sonali Bose
Fellow / Project Leader
Novartis

3:50-4:45PM
Meetings
iSolve & Networking Refreshments

iSolve-logo

4:45-5:15PM
Case Study
Biologicals
Minipiloting Tool: CFD Modelling of Commercial Scale Thawing Time from Small Scale Bags

bristol

      Understand DS/FDS thawing behavior and determine key model parameters
      Estimate DS/FDS thawing time scale-up parameters from small scale to commercial scale
      A mechanistic protein freezing and thawing model using CFD was developed to predict thawing behavior
      The model was successfully validated by predicting the thawing time in 6 L bag at commercial scale
      The thawing time is mainly controlled by latent heat (thawing) not by sensible heat
    Freezing Temperature does not significantly alter the thawing time

For biopharmaceuticals, time out of refrigeration (TOR) is a Critical Process Parameter (CPP) due to its instability upon exposure to ambient temperature. The parameters required for freezing and thawing of the frozen formulated drug substance (FFDS) needs to be thoroughly evaluated and optimized before transferring the process to commercial DP manufacturing site.
The thawing time of a monoclonal antibody has been studied in a 30mL bag to obtain difficult to measure parameters like heat transfer coefficient, heat capacity, conductivity and thawing heat which are same for any scale provided the material of construction, composition of substance being thawed and the thawing procedure are consistent.
These parameters are then incorporated into the thawing model for a commercial scale configuration (6 L bag) to predict the thawing time and temperature-time profile during thawing.
This model can also capture the change in liquid volume fraction with time and has the potential to accommodate both dynamic and static thawing

Mita Maity
Research Scientist
Bristol-Myers Squibb

Case Study
Innovation
Challenges and opportunities of development of salts of weak bases

pher

      • Effect of physicochemical properties of API and excipients
      • Implications of disproportionation on oral bioavailability
    • Alternative formulation approaches

A major challenge with the development of salts of weakly basic compounds is its propensity to dissociate to the free base form in the drug product, which may impact the quality and bioperformance of the product. A significant number of compounds in the discovery pipeline are weakly basic so continued effort is required in this area to investigate and understand the key factors and formulation approaches to mitigate these risks. This presentation will highlight the mechanistic understanding and gaps in salt disproportionation utilizing multiple case studies as examples.

Suman Luthra
Senior Principal Scientist
Pfizer

5:20-5:55PM
Plenary
An Inter-Company Perspective on Biopharmaceutical Drug Product Robustness Studies

shire

      DP robustness studies are essential in developing a commercial product that:
      • is not on the edge of stability failure
      • meets quality standards when formulation and process parameters are within allowed ranges.
      Through the use of DOE, relationships between formulation attributes and manufacturing process parameters are established, ensuring DP production consistently meets CQAs.
      BPOG survey and manuscript reviews and discusses the current industry status with regard to the scope, design and execution of biopharmaceutical DP robustness studies.
      Common themes and alignment opportunities were identified with regard to the use of DP robustness studies.
    Recommendations for best practices and harmonization are integrated in the case studies.

The BioPhorum Development Group (BPDG) is an industry-wide consortium enabling networking and sharing of best practices for the development of biopharmaceuticals. As part of the Formulation Point Share (FPS) activities, an inter-company collaboration exercise was performed with a focus on biopharmaceutical drug product (DP) robustness that included a bench-marking survey and extensive group discussions around the scope, design, and execution of robustness studies. The results of this industry collaboration reveals key common themes: 1) biopharmaceutical DP robustness consists of both formulation robustness and manufacturing process robustness; 2) robustness integrates the principles of Quality by Design (QbD); 3) DP robustness feeds into critical quality attribute (CQA) finalization, development of control strategies, and setting of commercial specifications; 4) most companies employ robustness studies, along with prior knowledge, risk assessments, and statistics to develop the DP design space; 5) studies are tailored to commercial development needs and the practices of each company. Three case studies further illustrate how a robustness study design for a biopharmaceutical DP balances experimental complexity, statistical power, scientific understanding, and risk assessment to provide the desired product understanding and process knowledge. Overall, the BPDG-FPS recognizes the industry challenges with regard to biopharmaceutical DP robustness, and presents some recommendations for best practices. This work may facilitate further industry conversations on biopharmaceutical drug development, with a favorable impact on industry alignment with regard to DP robustness studies. The manuscript is a composite view of opinions shared by the whole of the BPDG-FPS and should not be attributed to the individual positions of the companies.

James Kranz
Principal Scientist
Shire

5:55-6:00PM
Chair’s Closing Remarks

6:00-7:00PM
Evening Drinks Reception

Day 2 – August, 29 2017 – Tuesday
8:00-8:25AM
Registration

8:30-9:05AM
Plenary
Drug Delivery: Emerging trends and Opportunities

MedImmune

  • Evaluating how fast the delivery technology field has evolved until now –factors that will contribute to continued development
  • Potential of less-traditional delivery routes such as nasal and ocular delivery
  • Discussing the future of evolving areas including polymer technologies, auto injectors, microneedles etc.
  • Learnings and Opportunities

Anand Subramony
Vice President, New Product Technologies
Medimmune

9:10-9:45AM
Case Study
Biologicals
Non-Invasive Delivery Routes for Peptides: Focus on Successful Oral Technologies Progressing in the Clinic and Future Challenges
ipsen Due to their physicochemical characteristics, peptides are usually administered through the parenteral route, often several times daily. Injectable sustained-release peptide formulations based on biodegradable microparticles or implants have been very successful to enhance patient adherence and convenience, and increase safety and efficacy. They are likely to remain a significant and important part of the new peptide products coming to the market. However, the tremendous developments in alternative non-invasive routes of delivery are likely to result in more and more peptides being delivered by the transdermal, nasal, inhalation and oral routes. The main purpose of this talk will be to analyze and compare the various alternative non-invasive peptide delivery technologies progressing in the clinic, discussing the pros and cons of these technologies in regards to stability, bioavailability, safety/efficacy balance, impact on costs of goods and manufacturability. A special emphasis will be put on oral peptide technologies progressing successfully in the clinic, the key learnings from ongoing clinical studies and the future challenges anticipated for filing and launching oral peptide products in the next years.

Joel Richard
Senior Vice President, Peptides Development
Ipsen

Case Study
Small Molecules
A Two-Phase Dissolution-Partition Test for Characterization of BCS II/IV Drugs and Formulations
images
      • Characterize the aqueous super-saturation resulting from dissolution of amorphous solid dispersions
      • Use the aqueous media with pH alteration for ionic drugs
      • Assess the interplay among three kinetic processes: dissolution, precipitation and partition
      • Facilitate evaluation of key formulation variables and functional excipients
    • Demonstrate IVIVC for several BCS II and IV products

This presentation will focus on characterization of dissolution and partition profiles of poorly water soluble drugs and related formulations using a biorelevant two-phase dissolution-partition test. This test is designed to evaluate the dissolution of BCS II/IV drugs in an aqueous, biorelevant compartment that allows physiologically relevant pH changes with simultaneous partitioning (absorption) into a water immiscible organic phase. Case studies will be presented to demonstrate the utility of this method for evaluation of the super saturation and its relevance to in vivo exposure in humans. The presence of the “absorptive phase” in this the two-phase test appears to overcome shortcomings of conventional single-phase in vitro dissolution methods and therefore presents a great opportunity for establishing quantitative IVIVC in drug product development.

Ping Gao
Research Fellow
Abbvie

9:50-10:20AM
Solution Spotlight
Innovation
Role of CAPTISOL® (Sulfobutylether β-cyclodextrin) in enhancing the bioavailability of therapeutic agents

captisol

  • Enhancing bioavailability of therapeutic agents by the way of increasing their solubility is one of the commonly used pharmaceutical approaches. Incorporation of suitable permeation enhancers and excipients may be necessary to increase the bioavailability further, to deliver therapeutically required amounts of drugs. Sulfobutyl ether β-cyclodextrin has been known to form inclusion complex with water insoluble drugs to render them highly soluble. In addition to improving the solubility, Sulfobutyl ether β-cyclodextrin is also known to enhance the bioavailability of drugs by unique mechanisms that are attributable to its structure. A few case studies to demonstrate the influence of complexation with sulfobutyl ether β-cyclodextrin on the delivery of drugs via oral and topical routes will be discussed in the presentation.

S. Narasimha Murthy
Professor of Pharmaceutics
University of Mississippi

Solution Spotlight
Small Molecules
Formulation Insights for Solubility Enhancement: Striking the Right Balance

Patheon final_logo-01

  • This talk will provide an overview of Patheon’s Quadrant 2® platform for solubility enhancement of poorly soluble compounds. We have developed an in silico platform that utilizes the chemical structure of the API and known physico-chemical properties in order to guide the appropriate manufacturing Technology selection as well as excipient and formulation choices. The primary advantage of this approach is that it enables a faster, scientifically sound and cost-saving approach for formulation of poorly soluble drug molecules. Insights into navigating performance, stability and scale-up are presented via case studies.

Sanjay Konagurthu
Senior Director, PDS Global Science and Technology
Patheon

10:20-11:15AM
Meetings
iSolve & Networking Refreshments

iSolve-logo

11:15-11:45 AM
Case Study
Biologicals
Practical Considerations in Developing High Concentration Protein Formulations

Regeneron

    • Challenges and considerations: high viscosity, manufacturing challenge, device limitation, IP protection, etc.
    • Case studies in developing high concentration protein formulations
      1. Viscosity reducing strategies
      2. Balancing the viscosity reducing effect with stability
      3. DoE-based model understanding formulation viscosity vs. manufacturing variation to ensure consistent product performance

In recent years, there has been an increased demand for high concentration liquid antibody formulations to enable subcutaneous (SC) administration of therapeutic doses of antibodies or to facilitate a switch from a commercially approved, intravenously (IV) delivered product to a SC product for self‐administration from a pre‐filled syringe or autoinjector in a home setting. Achieving high concentration solutions of antibodies can be limited by high solution viscosity, presenting challenges for manufacturing, product stability, and administration. In this presentation, multiple case studies will be discussed that support strategies for developing high concentration antibody formulation products. Key development challenges include 1) optimizing stress conditions for high concentration formulations, 2) identifying viscosity reducing strategies and the impact on manufacturing process, and 3) defining a product viscosity profile using a DOE approach to select a formulation which meets delivery device requirements. The learnings from these specific case studies are generally applicable to any high concentration liquid antibody formulation development programs.

Qingyan Hu
Scientist
Regeneron Pharmaceuticals

Case Study
Small Molecules

Challenges and Opportunities of Developing Pediatric Drug Formulations
tevaDevelopment of pediatric oral formulations is no child’s play! In fact, it can be quite scientifically challenging as children differ from adults in many aspects of pharmacotherapy, including capabilities for drug administration, medicine-related toxicity, and taste preferences. It is prudent that pediatric medicines are formulated to best suit a child’s age, size, physiologic condition, and treatment requirements. New regulations and research initiatives have resulted in some progress in the development of pediatric formulations. Several challenges, however, still remain. Development of suitable dosage form to administer and taste-masking are two of the challenges unique for pediatric oral formulations and this session aims to address them in detail.

Suniket Fulzele
Group Leader, Formulation Development
Teva Pharmaceuticals

11:50-12:20PM
Solution Spotlight
Biologicals
High-Throughput Light Scattering Tools for Characterizing and Formulating Macromolecules and Nanoparticles

wyatt

        From aggregates to conjugates and peptides to polysaccharides, light scattering detectors combine with multiple sample preparation and delivery systems to provide a comprehensive suite of biophysical characterization tools. The light scattering toolkit determines molar mass, size, charge, interactions, conformation and conjugation of macromolecules and nanoparticles. This seminar presents an overview of the instrumentation and examples of the tasks relevant to well-characterized biopharmaceuticals that may be accomplished with these tools, focusing on three central techniques: µSEC-MALS-DLS, SEC-MALS-IV and HT-DLS.

Two of Wyatt’s light scattering tools contribute major productivity enhancements in a biopharmaceutical setting, greatly increasing the speed of analysis without sacrificing sensitivity: the µDAWN and DynaPro Plate Reader II.

        • The µDAWN adds multi-angle light scattering (MALS) and dynamic light scattering (DLS) capabilities to UHPLC, for enhanced resolution and speed in absolute molar mass determination. As will be presented in this seminar, all the standard SEC-MALS-DLS applications such as aggregate, fragment and protein conjugate analysis carry over to µSEC-MALS
        • The DynaPro Plate Reader II brings dynamic light scattering (DLS) to the realm of high-throughput, automated measurements of size, eliminating tedious cuvette-based measurements. In this seminar, the applications of the DynaPro for aggregation and stability studies will be presented

John Champagne
Senior Applications Scientist and Northeast Regional Manager
Wyatt Technology Corp.

Solution Spotlight
Small Molecules
Accelerating innovation in formulation science

cas_color - 150

      • Learn new methodologies for finding intersections in literature from which to innovate
      • Leverage work done by others to speed your time to market and reduce costs
      • Uncover insights on how to solve vexing problems, such as hardness, stability, and more
      • Use trend analysis to gain a vivid understanding of the marketplace and it’s changing landscape
    • Review examples of deep analysis on excipient and properties trends to uncover insights

Pillhun Son, PhD
Projects Coordination Manager
CAS

12:25–12:55PM
Case Study
Biologicals
Thermal Stabilization of Freezing Sensitive Adjuvanted Vaccine Formulations Through Spray Drying

sanofi Vaccination saves millions of lives each year, hence it is extremely important to maintain thermal stability and immunogenicity during manufacturing and cold chain storage of vaccines.

  • Spray-dry is an emerging technology recent increasingly investigated for biologics.
  • The POC study demonstrated that stable dried adjuvant-containing vaccine formulations can be successfully produced through spray dry for those freezing sensitive formulations, which often known easily decreased their immunogenicity during the conventional freeze drying process.
  • The physio-chemical properties were characterized and the potency was tested for the formulations.

Enhance vaccine product stability is a very challenging task for all formulation scientists. In the past, freeze drying is often used in vaccine industry as gold standard to stabilize labile products. However, freeze dry process can damage those vaccine products with freezing sensitive component(s) such as Aluminum salt(s) adjuvant and emulsions. To avoid this issue, spray dry can be a great potential alternative strategy. It is successfully demonstrated that the feasibility of applying spray dry technology to stabilize different type of antigens and freezing sensitive adjuvants. The dried products were characterized using a panel of assays. The data suggested product stability, antigen potency and adjuvant functionality were well maintained.

Lillian Li
Formulation Scientist, Bioprocess Research & Development
Sanofi Pasteur

Case Study
Small Molecules
Advances in Supersaturating Drug Delivery Systems

bristol

    • What are Supersaturating Drug Delivery Systems (SDDS)?
    • Advances in developing and characterizing SDDS?
    • Complexity in in-vitro and in-silico characterization of SDDS?
    • Benefits and limitations of SDDS characterization tools and methods

Supersaturating drug delivery systems (SDDS) such as amorphous solid dispersions and lipid-based formulations have been successfully used to enhance oral bioavailability of poorly water soluble compounds. However, in general, it has been challenging for pharmaceutical scientists to characterize these systems to establish a good in-vitro and in-vivo performance relationship. The supersaturation maintenance of SDDS is highly dependent on the complex interplay between pH, solubility, degree of supersaturation, high energy forms of drug and their interactions with excipients such as polymers and surfactants. Recent studies have focused on understanding various aspects of this complex interplay of biopharmaceutical factors. This talk will focus on the recent advances in the development of SDDSs and their application in bioavailability enhancement. It will highlight novel in-vitro, in-silico, and in-vivo methodologies to characterize the biorelevant performance of SDDS. The benefits and limitations of SDDS and their characterization methods will also be discussed

Dhaval Patel
Senior Research Investigator II
Bristol-Myers Squibb

12:55-1:55PM
Networking Lunch

Networking-Lunch-logo

Lunch & Learn Roundtable: Analytical Strategies for Formulation Development and Stability Assessment of Therapeutic Products

KBI_Logo (web version)

Formulation Development Strategies
      • Pros and Cons of conservative and aggressive approach for stability studies in support of formulation development (DOE as an example of aggressive approach)
      • Applying platform high throughput screening tools to identify critical factors: DSC, DLS and Unit/DSF
      • Applying semi-platform tool for long term stability prediction: HUNK/ICD
      • Using orthogonal techniques – essential in aggressive approach
The analytical toolbox
    • Forced Degradation studies: choosing the right methods for controlling quality and stability studies
    • Extended characterization techniques: structure elucidation and its impact on other methods selection
    • Assessing method suitability throughout product lifecycle, early to late phase: from method development to validation
    • Using orthogonal techniques – essential in aggressive approach
Advanced particle techniques for product characterization
    • Applying FDA approved techniques for particle characterization of test products in lieu of clinical studies
    • Novel techniques for characterization of nanoparticles and trace amounts of impurities in nanomedicines
    • Tiered approaches to particle characterization and identification (when and how techniques should be applied)
    • Establishing a particle profile for a biologic (importance of formulation, container, closure, and delivery devices)

Amber Fradkin, Ph.D.
Director, Particle Characterization Core Facility, Research and Development
KBI Biopharma

1:55-2:25PM
Case Study
Biologics
Nanoemulsion Intranasal Drug Delivery

nanobio

 

      • Intranasal drug delivery is becoming a very attract route to delivery therapeutic agents due to improved bioavailability, lower dose/reduced side effect, avoidance of the gastrointestinal tract and first pass metabolism.
      • Intranasal administration is an attractive option for local, lymphatic and systemic delivery of many therapeutic agents.
      • However, the mucosal layer provides an additional barrier to overcome for molecules to transverse via the intranasal route.
      • Nanoemulsions (NE: oil-in-water emulsions) containing nanometer-sized droplets stabilized by surfactants have been specifically designed for intranasal delivery.
      • Developed novel oil-in-water nanoemulsion (NE) formulations containing various cationic and nonionic surfactants for use as adjuvants for the intranasal delivery.
      • Tested formulations in high-throughput screens and found NE induced immunogenicity and antigen delivery are facilitated through initial contact interactions between the NE droplet and mucosal surfaces, which promote prolonged residence of the vaccine at the site of application, and thus cellular uptake.
      • Incorporating small molecule, peptides/proteins and large macromolecules in optimized nanoemulsion formulation for transmucosal delivery.
    • Nanoemulsions can delivery agents across the nasal mucosa for therapeutic effects.

Susan Ciotti
Director of Formulations
NanoBio Corp

Case Study
Small Molecules
Improving Oral Bioavailability by Solid Dispersions: A Case Study

Shionogi

      • An overview of OSPHENA®
      • Solid dispersions of Ospemifene with hydrophilic polymers, enteric coating polymers and surfactants prepared by solvent casting, spray drying, and melt extrusion show solubility enhancement ranged from 2 to 1000 fold
      • The spray dried solid dispersions are physically and chemically stable during stability study
    • Discuss the four formulations that were selected for animal PK studies

Jimmy Chen
Senior Director, Pharmaceutical Sciences
Shionogi

2:30-3:00PM
Case Study
Biologicals
Infusion Set Compatibility and Drug Delivery Challenges of High Potency Antibody-Drug Conjugates (ADCs)

ImmunoGen

      • Conjugated monoclonal antibodies may have altered solubility and solution stability profiles compared to native (e.g. unconjugated) versions.
      • ADCs exhibit relatively high binding to IV sets, inline filters and other materials used in dose preparation and delivery when compared to native antibodies.
      • High potency ADCs require lower doses than other drugs, however, low doses further contribute to IV set compatibility concerns (e.g. very small volumes may be dosed or larger volumes of dilute solutions are dosed).
      • Low drug concentrations challenge the analytical capabilities of methods used to assess product quality following delivery.
      • The dosing range required for clinical development of ADCs is generally so broad that many dosing techniques are required (IV push, syringe & syringe pump or IV bag & pump delivery).

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.

Amy Leung
Scientist I
Immunogen

Case Study
Small Molecules
Nanoparticle Formulation Development: A Closer look at Pharmaceutical Fabrication Methods

phzer

      • Parenteral formulations using strong co-solvents create toxicity
      • Nanoparticle formulation for drugs with poor aqueous solubility are a safer alternative
      • Comparison of nanoparticle fabrication methods and composition

Many small molecule drugs developed in the pharmaceutical industry exhibit poor aqueous solubility and are difficult to formulate for parenteral administration. Since early pre-clinical studies for efficacy evaluation often require parenteral formulations, solubilization approaches using strong co-solvents are often used, causing toxic side effects. Nanoparticles offer a safer, fit-for-purpose parenteral formulation platform for drug solubilization to support early screening of these molecules. As interest in this platform has increased, the use of efficient fabrication methods and technology for nanoparticle production has become an important aspect of their pharmaceutical development. This presentation will show the effects of different nanoparticle fabrication methods and composition on resulting nanoparticle physical properties. Case studies using poorly soluble model drugs will be shown with various nanoparticle formulations.

Ghazal Hariri
Senior Scientist
Pfizer

3:05-3:45PM
Plenary
Recent advances in siRNA delivery for resistant cancers
bouve_logo
      – siRNA has low stability and poor pharmacokinetics
      – siRNA can be stabilized and its pharmacokinetics can be improved by using certain nanosystems capable of incorporation siRNA
      – stabilized siRNA can be used to downregulate the expression of proteins involved in drug resistance of cancer cells
    – nanopreparations of siRNA can also be redesigned for combination cancer therapy

siRNA is a powerful tool to control cellular processes at a post-transcriptional level. Although siRNA can be used as potential therapeutic agent for different diseases (including cancer), its therapeutic application is still limited because of its instability against nucleases and poor pharmacokinetics. With this in mind, we suggested a novel polymer-lipid-based approach to stabilize and deliver siRNA. We have modified a double-stranded GFP-siRNA with a phosphothioethanol (PE-SH) via the disulfide bond and prepare mixed micelles from such conjugate and polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate in order to increase siRNA stability against nucleases and allow for siRNA liberation when inside cells because of the reduction of the –S-S-bond by high intracellular glutathione. siRNA-containing polymeric micelles have been shown to dramatically increase its stability against enzymatic degradation and were able to release free siRNA in the presence of glutathione. We have studied a silencing effect of such micelles after incubating it with C166-GFP endothelial cells. The siRNA-lipid conjugate-containing PEG-PE micelles were well taken up by cells resulting in strong down-regulating of the GFP production in C166-GFP endothelial cell line (50-fold more than the same quantity of the native siRNA. At the same time, the cytotoxicity of such preparations is very low. Similar results can be achieved by using PEG-polyethyleneimine-lipid conjugate for condensing and protecting siRNA. Resuting nanopreparations of siRNA can be used for therapy of multidrug resistant cancers by using siRNA down-regulating the production of proteins involved in cancer cell resistance. Furthermore, such preparations can be used for combination drug/gene therapy of such cancers.

Vladimir Torchilin
PhD, DSc University Distinguished Professor Director
Center for Pharmaceutical Biotechnology and Nanomedicine Northeastern University