September 18-19, 2023; Boston, MA

For speaking opportunities please contact ahmed.osman@markallengroup.com

7:30 AM - 8:25 AM

Registration & Refreshments

8:25 AM - 8:35 AM

Chair’s Opening Remarks

8:35 AM - 9:05 AM - Keynote

Technology & Innovation

Mesoporous Silicon and Silica Nanomaterials for Drug Delivery Applications

Prof. Michael Sailor, Distinguished Professor of Chemistry and Biochemistry, University of California, San Diego

  • The oxide chemistry of mesoporous silicon nanoparticles allows dynamic restructuring of the mesopores to sequester protein therapeutics
  • The chemistry provides a means to protect biologics against proteolytic, nucleolytic, or hydrolytic degradation
  • Peptide targeting groups provide a means to home nanoparticles to selected tissues while minimizing immune system responses.
  • Multiple copies of a peptide targeting group on a single nanoparticle enhances binding via multivalent interactions
Porous silicon nanoparticles possess an oxide chemistry that is well suited for loading and delivery of biologics (antibodies, enzymes, and nucleic acids). The material can be tuned for either slow release or for triggered release, depending on the specific chemistries and coatings used. Attachment of peptide targeting groups provides a means to direct delivery of therapeutic payloads to selected tissues.  One area with an unmet therapeutic need is in the treatment of antibiotic-resistant bacterial infections, and the deployment of porous silicon nanoparticles to meet this challenge will be described. The intrinsic photoluminescence that derives from quantum confinement in the silicon skeleton provides a built-in luminescent probe that can be used for in vivo and in vitro tracking and self-reporting drug delivery in these systems.

9:10 AM - 9:40 AM - Case Studies

Small Molecules

Melt Spray Congeal Microspheres: A Flexible Oral Multiparticulate Platform for Patients

Sheri Shamblin, Director, Pfizer

  • Pharmaceutical development pathway integrating patient needs, development considerations and physico-chemical/biopharmaceutical compound profile
  • Integrated CMC platform from developability assessment, formulation design and process optimization leading to a robust commercial dosage form
  • Case studies showcasing how an integrated CMC platform can accelerate timelines

Biologics

Overcoming Formulation Challenges for Complex Bispecific Antibody Drug Product Development

Xiaofeng Lu, Principal Research Scientist, AbbVie

  • Challenges in formulation development for complex bispecific antibodies
  • Bispecific antibody case studies ​
  • Aggregation- a critical product quality attribute and possible causes  ​
  • Control aggregation by non-platform formulation and process parameters  

Technology & Innovation

9:45 AM - 10:15 AM - Case Studies

Small Molecules

Formation and Inhibition of Nitrosamines in Drug Product

Kausik Nanda, Principal Scientist , Merck

Nitrosamines, in the absence of toxicological data, are regarded as potential mutagens, and ICH M7 considers N-nitrosamines as part of the highly mutagenic cohort of concern. Recently, several drug withdrawals have been resulted from the contamination of drugs with nitrosamines. To ensure patient safety and access to life saving drugs, it is important to understand the phenomenon of the formation of nitrosamines in drug products and how to inhibit the formation of nitrosamines in drug products. We will present data, primarily, on the formation and inhibition of formation of nitrosamines in solid oral dosage form.

Biologics

Biopharmaceutics Aspects on Long-Acting Injectables Drug Products

Jun Zhang, Director, Drug Product Formulation and Process Development, Affinivax

10:20 AM - 10:50 AM - Solution Spotlights

Small Molecules

Solution Spotlight by Quotient Sciences

Biologics

Solution Spotlight by Amneal Pharmaceuticals

Device Development

Direct-to-Organ Drug Delivery – Opportunities, Challenges, and Ideas

Harshal Shah, BioPharma Sector Head, Cambridge Consultants

Tim Phillips, Principal Human Factors Engineer, Cambridge Consultants

R&D pipeline across the biopharma industry is diversifying at rapid pace with new modalities and new class of drugs becoming significant part of their overall research strategy.  Increasingly we are observing a need for delivering drug locally in difficult to access anatomy such as heart, brain, spine, kidneys across different therapeutic areas including oncology, CNS, autoimmune and number of rare diseases. The preference will  always be to delivery these drugs with minimally invasive approach. Our team evaluated challenges involved in developing device technologies and new procedure for delivering such complex drugs localized to organs, tumours or tissues and developed innovative ideas and concepts that could be deployed in specific situations. This talk will focus on few select ideas and our thought process in design and development of such delivery platforms and procedures.

10:50 AM - 11:40 AM

Networking & 1-2-1 Meetings

11:40 AM - 12:10 PM - Case Studies

Small Molecules

Predicting Powder Flow Obstruction in Solid Dosage Form Manufacture

Chen Mao, Distinguished Scientist, Small Molecule Pharmaceutical Sciences, Genentech

  • Powder flow obstruction, such as arching or ratholing, is a prevalent occurrence in the manufacture of solid dosage forms.
  • Accurate prediction of powder flow obstruction requires the knowledge of both powder flowability and stress condition of the powder in the equipment.
  • The risk of powder flow obstruction is highest under the active stress state.  Traditional Jenike methodology in hopper design assumes the passive stress state and could therefore under-predict the powder flow risks.
  • Additional insights of powder flow risks, such as stress heterogeneity and flow pattern, can be obtained via FEM analysis.

Biologics

Long-Acting Injectables – Biopharmaceutics and Drug Product Design

Simone Alidori, Scientific Leader & Associate Fellow, GSK

  • Cross-functional approach for LAI product design and development.
  • Mechanistic understanding of LAI performance
  • Integrated biopharmaceutics concepts and opportunities
  • Enterprise vision for LAI drug product development
 
This presentation will cover Long-Acting Injectables (LAIs) as a novel way to design and deliver patient-centric medicines. Mechanistic understanding around LAI product performance is required to ensure efficient design and development of patient-centric and stable drug product with robust control strategy. Integrated biopharmaceutics concepts will be discussed to build mechanistic understanding and drive differentiated product design.

Device Development

Challenges and Opportunities in Combination Product Design, Development and Use

Scott Nunn, Director, Device Development , Gilead

12:15 PM - 12:45 PM - Solution Spotlights

Small Molecules

Solution Spotlight by Sever Pharma Solutions

Biologics

Solution Spotlight by Croda Pharma

Technology & Innovation

Solution Spotlight by Celanese

12:45 PM - 1:45 PM

Networking Lunch

Lunch & Learn Roundtable

Roundtable by WL Gore

1:45 PM - 2:15 PM - Case Studies

Small Molecules

End to End Digital Design for ER Tablet Drug Delivery Systems with Functional Coating

Alfred Berchielli, Formulation and Process Scientist , Pfizer

  • Selection of the drug delivery technology and modelling of the target release profile.
  • Examples of initial digital design for osmotic pump ER formulations in early phase clinical studies.
  • Enhanced control of film properties and dissolution via comprehensive process modelling and PAT for function coatings.
  • Scale-up and optimization of the functional coating process via first principles, empirical, and digital twin simulations from lab to commercial scale.
  • Eliminating or minimizing scale-up by use of the small batch or semi-continuous processes for functional coatings.



PK modelling has long been used to generate the target in-vivo release and PK profiles.  The drug delivery technology is then selected or matched with the biopharmaceutical objectives and patient medical need.  Formulation models have enabled digital design for initial prototype key attributes (e.g., functional coating weight gain) to achieve the target in-vitro dissolution profile.  More recently coating models have advanced to guide in scale-up from lab through commercial scale via first principles, empirical models and more comprehensive digital twins coupling the discrete element method (DEM) and computational fluid dynamics (CFD).  These models and new process analytical technology (PAT) are helpful to maintain consistent product performance by reducing variability in functional coating amounts or changes in coating morphology with process scale (e.g., batch size) or equipment design.  Additionally, there are new, small scale coating equipment designs that can be leveraged to reduce or avoid scale-up altogether.

Biologics

Accelerating Discovery to FIH through Early Formulation Risk Assessments of Novel Biologics

Suman Luthra, Director Discovery Pharmaceutical Sciences, Merck

  • Inform candidate selection by evaluation of structural liabilities of lead candidates​ against target candidate profile
  • Develop prototype product concepts to accelerate clinical formulation development

Device Development

Development of Drug Delivery and Photoactivation Devices for the Treatment of Bladder Cancer

Keith Faucher, Senior Director Device Development and Innovation, Aura Biosciences

  • Performing front end research to understand the clinical environment for administering combination product therapy.
  • Defining device development requirements based on the limitations of clinical and drug product characteristics.
  • Importance of obtaining early user feedback on device prototypes and procedures.
  • Strategies for device sourcing and testing to speed evaluation of combination products in clinical trials.

2:20 PM - 2:50 PM - Case Studies

Small Molecules

Pediatric Formulation Design – From Adult to Children

Curtis Leung, Senior Scientist, Agios

  • Agios’ approach for pediatric formulation design
  • Pediatric formulation platform selection
  • Palatability and excipient selection
  • Manufacturing and packaging consideration

Biologics

Characterization of the Hydrolytic Activity of Polysorbate Degrading Host Cell Proteins

Anthony Tomlinson, Technical Development Principal Scientist

  • Polysorbate degradation as a topic will be introduced
  • The identification and purification of polysorbate degrading hydrolases
  • Screening of these enzymes for their degradation activity
  • Characterization of enzyme kinetics and specificity on a subset of hydrolases

 Polysorbate degradation is an industry-wide issue for biopharmaceutical drug product development. This degradation can be catalysed by the low-level presence of hydrolytic host cell proteins which co-purify with the target molecule in bioprocessing. The degradation of this key excipient can cause a variety of issues, including loss of surfactant activity and the formation of subvisible or visible products in liquid formulations. In this work, we aimed to purify and characterize several CHO cell host cell proteins with respect to their ability to degrade polysorbate.
 

Device Development

Evaluation of External Technologies for Device and Delivery Technologies

Ajit D'Souza, Director, Combination Product Development, Kiniksa Pharmaceuticals

2:50 PM - 3:40 PM

Networking & 1-2-1 Meetings

3:40 PM - 4:10 PM - Solution Spotlights

Small Molecules

Solution Spotlight by Ligand Pharmaceuticals

Biologics

Solution Spotlight by Precision NanoSystems

Device Development

Solution Spotlight by EdgeOne Medical

4:15 PM - 4:45 PM - Case Studies

Small Molecules

The Future of Assessing Oral Absorption Potential and Developability Risk in Drug Discovery

Maya Lipert, Principal Scientist

  • An overview of common developability assessment tools utilized to differentiate molecules based on oral absorption potential during drug discovery.
  • Novel computational approaches to augment in silico developability assessment including quick crystal structure predictions and crystalline solubility predictions.
  • Use of automated platforms for robust in vitro physicochemical profiling data to facilitate developability assessment on limited material.    

Developability assessment related to determining the oral absorption potential of small molecules is not a new concept.  The Dose Number (Do) concept was published by Amidon and coauthors in the 1990’s and the Developability Classification System (DCS) by Butler and Dressman followed in the 2000’s.   It is established how to use these concepts that rely on human dose and simple in vitro parameters like solubility and permeability to assess oral absorption risk and provide guidance on formulation strategy.  What has evolved is usage of such concepts earlier in the drug discovery process to differentiate molecules, influence chemical series prioritization, and guide chemical design.  However, gathering high-quality data on the volume of molecules present this early in the discovery process remains a barrier to leveraging Do and DCS to influence chemical design.  Here, we discuss emerging computational approaches that can predict properties relevant to oral absorption and automated platforms that enable teams to get robust data at the right time enabling earlier developability assessment.

Biologics

A Biopharmaceutics Perspective on Oral Delivery of Peptides, Proteins and Oligonucleotides

Manuel Sanchez-Felix, Associate Director, Novartis Institute for BioMedical Research

The following topics will be discussed related to oral bioavailability of large molecules

  • Barriers to oral absorption of large molecules
  • Oral biopharmaceutic mechanisms applied in formulation approaches
  • Review of the oral formulation approaches will be discussed
  • Recent formulation advancements

Device Development

Formulation and Device Considerations for Subcutaneous Delivery

Steven C. Persak, Director, Device Development/MRL , Merck

Will Forrest, Principal Scientist, Sterile & Specialty Products, Merck

  • Overview of subcutaneous delivery in the current market
  • Considerations when developing a target product profile for subcutaneous delivery
  • Identifying early challenges and opportunities in formulation and device development
  • Technology down selection and moving forward towards the target image

4:50 PM - 5:20 PM - Case Studies

Small Molecules

Small Molecule Crystallographic and Modeling Strategies to Improve Solubility

Tina Xiong, Associate Principal Scientist, Merck

Show more

Biologics

Topic TBC

Device Development

Topic TBC

5:20 PM - 6:00 PM - Panel Discussion

Technology & Innovation

Preparing for Patient-Centric Drug Development Regulations

Nélio Drumond, Associate Director, Lead Process Scientist, Global Manufacturing Sciences, Drug Product, Takeda

  • What do the recent FDA Guidelines on Patient-Focused Drug Development (PFDD) mean to us?
  • Why do we need more patient focussed thinking and design of drug products, medical devices and combination products?
  • How will become more patient focussed shake up the industry and make us more competitive

6:00 PM - 6:10 PM

American DDF Poster Presentation Award & Chair's Closing Remarks

6:10 PM - 7:10 PM

Drinks Reception

8:00 AM - 8:15 AM

Registration & Refreshments

8:15 AM - 8:20 AM

Chair’s Opening Remarks

9:10 AM - 9:40 AM - Case Studies

Small Molecules

Impact of Crystallinity on Performance of Amorphous Solid Dispersions

James DiNunzio, Director, Merck

  • Origins of crystallinity in amorphous solid dispersions
  • Detection approach and control strategies to minimize risk
  • Assessing impact of crystallinity on in vitro and in vivo performance of amorphous solid dispersions.

Biologics

Peptide Nanoparticles as an Approach for Stable High Concentration Formulations

Dennis  Leung, Director and Manager of the Discovery Pharmaceutics and Preformulation , Genentech

  • Peptides have emerged as a promising therapeutic modality, but present unique challenges are involved in formulation development, particularly at high concentrations that may be required for convenient administration routes such as subcutaneous injectable delivery, including:  variable and potentially low solubility, precipitation, aggregation, high viscosity, among others
  • Stable peptide nanoparticles in water can enable stable and doseable formulations without the need for harsh excipients
  • A novel and general process has been identified for preparing peptide nanoparticles at high concentrations without causing stability risks or degradation, which works on a wide range of diverse peptide species.

Technology & Innovation

Inflammation-Responsive Supramolecular Gels for Controlled Drug Delivery

Nitin Joshi, Assistant Professor , Harvard Medical School

9:45 AM - 10:15 AM - Solution Spotlights

Small Molecules

Solution Spotlight by Nanoform

Biologics

Solution Spotlight by TBC

Technology & Innovation

Solution Spotlight by Ardena

10:20 AM - 10:50 AM - Case Studies

Small Molecules

HPBCD as an Excipient in Low Dose Protein Formulations

Shreya Kulkarni, Senior Scientist II, AbbVie Biotherapeutics

  • HPBCD as an excipient to improve protein stability
  • Use of HPBCD in lyophilized protein formulations
  • Interaction of HPBCD with formulation excipients like surfactants

 

Biologics

Developability Assessment of Biologics and Formulation of Novel Molecules

Luis Brito, VP Delivery Platform, Beam Therapeutics

Technology & Innovation

Fixed-Dose Combination (FDC) Drug Production Development

Zhi Chen, Associate Scientific Director, Bristol Myers Squibb

10:50 AM - 11:40 AM

Networking & 1-2-1 Meetings

11:40 AM - 12:10 PM - Case Studies

Small Molecules

Enabling or Not? – A Journey of FIH Formulation Development for a Poorly Water-Soluble Deuterated Weak Basic Development Candidate

Yan  He, Head of Early Formulation Development, Sanofi

  • Bioperformance driven and physico-chemical properties-based formulation development
  • Spring effect in conventional formulation - Evaluation and selection of acidic excipients to provide a micro-environment to offer higher solubility in gastric fluid
  • Parachute effect in conventional formulation - Evaluation and selection of polymers to sustain the dissolved molecules in intestine fluid
  • Prototype formulation development using pentagastrin treated dog exposures to help select the best performer
  • Enabling formulation, Amorphous solid dispersion formulation, development to be a backup option
  • Stability evaluation using ASAPprime® for shelf-life determination and packaging configuration selection

Biologics

Formulation & Process Development Considerations for Non-Viral Gene Delivery

Amey Bandekar, Associate Director - Biologics Drug Product Development & Manufacturing , Sanofi

Comirnaty® and Spikevax® along with siRNA-LNP based Onpattro® have demonstrated the manufacturability and clinical viability of LNP based nanocarriers. In development of LNP based drug product, the choice of each lipid component and the manufacturing technology is one of the key factors for success. The choice of lipid matrix can be modulated to maneuver and change the biodistribution of LNPs depending on the organ of interest and type of nucleic acid. The manufacturing technology can have significant impact on the biophysical properties, structural characteristics, colloidal stability, and efficacy of the LNP. This study describes the key considerations for designing LNP formulations and impact of different manufacturing parameters and the scale up consideration to enable successful LNP drug product manufacturing.

Technology & Innovation

Development of ASD Formulation for Clinical Studies – From Amorphous Theoretical Solubility Calculation to ASD Tablet Development

Wei Zhang, Principal Scientist, Small Molecule Pharmaceutics , Genentech

Amorphous formulation becomes an attractive strategy to deliver poorly water soluble drugs owing to its higher solubility. This presentation will cover three major topics for amorphous drug product development to support clinical studies – (1) theoretical solubility calculation for amorphous drugs; (2) effect of ASD composition on the disintegration and drug release of ASD tablets; (3) a case study of developing an ASD formulation to improve bioavailability and mitigate mechanical instability risk of crystalline form for early phase clinical studies. The first topic will discuss different methods of calculating amorphous drug solubility and the experimental evaluation of these equations. Based on the evaluation, one calculation equation was recommended based on the overall accuracy and complexity. The validated amorphous solubility calculation provides a guidance for ASD composition screening and developing ASD formulation. To successfully apply ASD formulation in clinics, final dosage form (e.g. ASD tablets) is usually needed. Owing to great amount of polymers in the ASD composition, the disintegration and drug release usually become an issue for ASD tablets especially when ASD loading increases. The second topic will discuss how polymer type, ASD loading in tablet and polymer-drug ratio affect the disintegration and drug release of ASD tablets. At last, the third topic will present a case study of developing an ASD tablet, guided by amorphous solubility calculation, to improve the drug bioavailability and mitigate mechanical instability risk of the selected crystalline form. To summarize, the overall goal of this presentation is to provide an industrial perspective for the design and formulation of amorphous drug products based on fundamental understanding of amorphous materials.

12:15 PM - 12:45 PM - Solution Spotlights

Small Molecules

Solution Spotlight by WuXi STA

Biologics

Solution Spotlight by Hovione

Device Development

Solution Spotlight by Gerresheimer

12:45 PM - 1:45 PM

Networking Lunch

1:45 PM - 2:15 PM - Case Studies

Biologics

Physiologically-Based Biopharmaceutics Modelling to Inform Drug Product Quality and Clinical Decisions

Filippos Kesisoglou, Distinguished Scientist, Pharmaceutical Sciences and Clinical Supply, Merck

  • Recent developments on application of PBPK/PBBM models to inform bioequivalence decisions
  • Linking dissolution to clinically relevant specifications
  • Use of PBPK modelling to understand food effect after formulation changes
  • Emerging use of PBPK modelling to understand excipient interactions

Device Development

Microneedles Based Drug Delivery System

Harshil Parikh, Principal Scientist Formulations, Actavis

2:20 PM - 2:50 PM - Solution Spotlights

Small Molecules

Solution Spotlight by Lubrizol

Biologics

Solution Spotlight by TBC

Device Development

Solution Spotlight by TBC

2:50 PM - 3:30 PM

Networking & 1-2-1 Meetings

3:30 PM - 4:00 PM - Case Studies

Small Molecules

Integrated Pre-Formulation and Drug Product Characterization Efforts Leading to Nimble Advancement of Drug Candidates to Human Clinical Trials

Gaauri Naik, Director, Pharmaceutics, Relay Therapeutics

The development cost and timeline for a new drug is increasing due to high attrition rates caused by inadequate physicochemical and biopharmaceutical attributes, unacceptable safety, and sub-marginal efficacy. This development attrition rate can be reduced by strengthening non-clinical formulation screening process and establishing a drug product developability assessment plan to enable nimble selection of developable compounds to move to the clinic. It is critical to select the right formulation principles, and equally important to run developability screens by:
  • Physiochemical characterization of new chemical entities’
  • Salt form and polymorph form selection
  • Preclinical formulation development
  • Integrated non-clinical formulation testing and profiling
  • Drug delivery technologies to enable oral bioavailability of poorly water-soluble compounds 

Technology & Innovation

Current Challenges During CMC Development and Delivery of Novel Modalities

Cesar Calero, Senior Scientist Biologics Drug Product Development & Manufacturing, Sanofi

The expansion of biopharmaceuticals into so called “novel modalities” have encountered new challenges and opportunities during CMC development and clinical administration/drug delivery. This presentation will cover some of the pain points for novel modalities and highly potent (low dose) biotherapeutics, considerations for Drug Product design, formulation, manufacturing, and compatibility in-use studies, and case studies for early clinical studies

4:00 PM - 4:30 PM - Keynote

Technology & Innovation

4:45 PM - 4:50 PM

Chair’s Closing Remarks