Post on 19-Mar-2020
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Presentation Outline
• Overview of Particle Sciences
• Corporate Partnerships
• Licensed Technologies
• Development Model
• Select Technologies
• Select Current Projects
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Introduction
• CRO servicing Pharmaceutical and Biotech companies
• Providing formulation/drug delivery, analytical services and clinical trial material production
• Founded in 1991, privately held, profitable
• Bethlehem, PA, 15,000 sq ft, 40+ employees
• Comprehensive formulations approach
• State-of-the-art chemical and physical characterization methodologies
• cGLP/cGMP, analytical/bioanalytical laboratories
• cGMP clinical trial materials production for both sterile and non-sterile products
• Full ICH stability programs
• Dedicated highly potent compound handling infrastructure
• DEA licensed, FDA registered
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Broad Base of Experience
• MD and PhD’s in: Physical Chemistry, Medicinal Chemistry, Synthetic Organic Chemistry, Material Science, Biomaterials, Analytical Chemistry, Colloids and Polymers, Physical Bioorganic Chemistry ……
• Director level oversight of analytical, quality, formulation, clinical and cGMP production groups
• Broad industry experience: international, large/small Pharma, biotech, government, not-for-profit
– Small molecules, oligos, peptides, proteins
– Multiple therapeutic areas
• Multiple commercialized technologies
• > 100 patents pending / issued ranging from nanoparticles to medical devices
• Regulatory, US and foreign CMC section support
• Technology transfer of multiple technologies
• Nanoparticle design
• Instrument/device design
• Many peer reviewed publications
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Particle Sciences’ Role
• From post-discovery through clinical development• Work under multiple models• Prefer to be an integrated member of the team• Routine work through true innovation/invention
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Integrated Approach
• Full development program management• Multiple integrated disciplines
– Formulation– Analytical/Characterization– Regulatory support– Production
• Responsive• Interactive / Open• Clients ranging from early venture-backed companies to
not-for-profit to large Pharma• Track record of innovation and of developing
commercializable technologies
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Formulation/Process Equipment
• Hydraulic and electric injection molders (lab and pilot scale)
• Compounder / Extruder (lab and pilot scale)
• Pelletizer
• Class 10,000 and Class 100 clean rooms
• Laminar flow hoods
• Laboratory homogenizer
• Admixer
• Microfluidics® high pressure homogenizer
• Microfluidics Reaction Technology™ system, MRT
• Three ultrasonic dispersers / Homogenizers with in-line capability
• High energy media mill
• Two 1.5 liter jacketed double planetary mixer with vacuum
• Two mini-spray dryers with organic solvent capability
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Formulation/Process Equipment
• Several micronizers with sanitary collector capability
• Augmented Drip Casting ADC™
• Roller mill
• Laboratory homogenizers
• Lyophilizers
• Bench-scale tangential flow filtration unit
• Three 500 gallon jacketed stainless tanks
• Three 100 gallon self-fired stainless tanks
• Glass-lined jacketed and pressurized reactor
• Cooling tower with 2 heat exchangers
• USP water treatment system
• Multiple stability chambers
• Autoclave
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Analytical / Bioanalytical Tools
• HPLC, UPLC• Microwave extraction• LC/MS Ion Trap• LC/MS Triple Quads• NMR, SEM, XRPD by third parties• UV/Vis• FTIR• DSC• Microscopic image analysis• Raman imaging with particle size/morphology integration • Fluorophotometer• Percutaneous absorption (IVRT)• ELISA• USP Dissolution Apparatus• Karl Fischer – Volumetric and Coulometric
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Physical Characterization
• Particle Sizing– Laser light scattering (DLS)– Fraunhofer diffraction (wet/dry)– X-ray and photo disc centrifuge sedimentometry– Optical counting (SPOS)– Image analysis
• High Throughput Particle Size Analysis (DLS)– Screening for protein stability / aggregation
• Zeta Potential– Electrophoretic light scattering– Phase analysis light scattering– Streaming potential
• Rheology– Oscillating rheometer– Rotational viscometer– Tack & compressive force
• Raman with particle size/morphology analysis• Advanced Instruments 3320 Osmometer• Shimadzu DSC-60• Kruss Contact Angle/Surface Energy Measuring
System G10• Turbiscan sedimentation-stability analyzer
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ICH Stability
• ICH Stability– Long term & accelerated conditions (T/RH controlled chambers)
• 25 °C/60% RH, 30 °C/65% RH, 40 °C/75% RH
– Photostability
– Stress stability 50 °C/85% RH
– Freeze / Thaw
• Custom Programs
• Developmental Stability Studies– Homogeneity via Raman spectroscopy
– Forced degradation
• MSn structure elucidation
• API/Drug Product
– API/Excipient compatibility via
• DSC
• HPLC
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Corporate Partnerships
Through partnerships, PSI strives to bring best of breed technology to bear on Clients’ projects. For example:
• Leading medical polymer supplier to streamline supply chain and offer new chemistries
• Microfluidics:
– Best in class high pressure homogenizers
– MRT for controlled precipitation of nanoparticles
• Horiba: collaborating to integrate optical microscopic imaging system (Clemex) with Raman spectroscopy (XploRA) to meet coming regulatory demands
• Malvern: collaborating on high throughput DLS system (APS) to speed large molecule formulation and stability screening
• IES Engineers: serve as PSI’s Chemical Hygiene Office, band compounds, and evaluate new processes from an EHS perspective
• Lehigh University: Development of novel bio-based surfactants to enhance drug solubility and penetration
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Licensed Technologies
• PSI believes in a multi-platform approach to best address our client’s challenges.
• PSI uses standard technologies, actively develops its own delivery technologies and in-licenses where strategic.
• Examples of recently in-licensed technologies include:
– Proprietary solid solution technology using GRAS amphiphilic polymers
– PEGylated cationic polymers: family of compounds with a wide range of uses – freedom to operate an important aspect of this portfolio
– Naturally derived biodegradable polymers: green materials suitable for sustained release IM/SC/IP dosage forms
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Development Model
• Technology centered to drive efficiency
– PSI has developed a skill/knowledge set around various technologies that enhance drug delivery
– PSI applies these technologies to a variety of dosage forms
• Solubility Program: leveraging Hansen Solubility Parameters and a proprietary solvent database spanning a wide range to accurately determine HSP values for a given material
• Design of Experiments: PSI has institutionalized use of JMP software for screening, characterization, and optimization studies as part of QbD program
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Particle/Microcapsule Design
• Extensive experience in particulate
design
• Company-wide core competency for
15 years
– Multiple successful efforts with large
commercial entities
– Ph.D. work of several staff members
– Both physical and chemical methods
• Production
– Scaled to 100,000’s kg per year
– Nanoparticle production
– Surface modification
– Microencapsulation
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Select Technologies- Spray Drying
• Bucchi B-290 (2)• Capable of handling aqueous and non-aqueous
systems
• Increases bioavailability by converting API into amorphous state, nanoparticles, or a combination of these two forms
• Good for Biopharmaceutical Classification Systems II and IV molecules
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Select Technologies- Augmented Drip Casting
• Applications: taste masking, capsules, pediatric dosage forms, combination products, highly controlled IM/SQ release
• Uniform, solid microspheres or core-shell microcapsules
• 10’s to 100’s in diameter
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Select Technologies- Hot Melt Extrusion
• Haake compounder/extruder
• Leistritz 18 mm twin screw extruder
• Increases bioavailability by converting API into amorphous state, molecular solution, nanoparticles, or a combination of all three
• Good for Biopharmaceutical Classification Systems II and IV molecules
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Select Technologies- Drug Eluting Devices
• Increasing demand
– Patent extension
– Local and systemic delivery
– Improved pharmacokinetics• Chronic systemic
• Local high concentrations
– Improved compliance
• Thermoplastic (EVA, PU)
• Thermoset (reactive silicones)
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Select Current Projects
ANDA program for intravaginal ring
• Multinational Pharma contracted PSI to conduct complete
development program for contraceptive intravaginal ring
– PSI has infrastructure to handle highly potent compounds,
including hormones
• After scale up, PSI will transfer manufacturing technology
to Client
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Select Current Projects
Pediculicide: Phase I (III in 2010)
• Complete formulation semi-solid (on/off shampoo)– High aesthetic demand
– Desired increase in efficacy
• API method development
• Drug product method development
• Participate in preclinical and clinical testing protocol design
• Production of GLP and GMP materials
• Full stability program
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Mucosal delivery of ARV’s: Phase II (III in 2011)• Complete formulation of multiple semi-solid formats
– High aesthetic demand• Multiple consumer tests
– Expensive API(s)• Inexpensive formula/applicator
– Demanding stability profile
• Scale up and all analytical method development
• Production of tox and clinical materials
• Full stability program
• Extensive regulatory support
• Extensive external laboratory coordination
Select Current Projects
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Select Current Projects
Novel ophthalmic excipient
• PSI developed novel cationic PEGylated excipients for
multiple applications, including ophthalmic
• Phase I for dry eye has demonstrated statistically significant
advantage for tear break up compared to commercial
product
• Several Companies are interested in a variety of potential
applications – dry eye, incorporation of excipient into
devices, stabilization of antibodies…
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Novel Dermal Filler
• Issue: Novel modified polysaccharide technology for sub-
dermal filler gel containing biodegradable microparticles
• Resolution: Transferred in polymer technology (chemistry
and processing), and developed prototype gel formulations
and microparticles.
• Outcome: GLP formulations prepared for mini-pig tolerability
study. Good study outcome. Technology available for
license.
Select Current Projects
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Select Current Projects
Improved bioavailability of an oral chemotherapeutic
• Issue: Repurposed potent, BCS II API with poor (1%) oral
bioavailability, CTM required for P1 trial, and route to
conversion of dosage form to an oral solid
• Resolution: Reformulate using both nanoparticle and
microemulsion approaches for eventual conversion into
solid dosage form
• Outcome: Produced CTM from successful candidates
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Select Current Projects
Oncology agent with novel MOA for IV administration
• Issue: toxicity of particulate formulations developed by three
different academic institutions
– Full characterization of academic formulations showed they
were not what they were purported to be
• Resolution: filled in gaps in preformulation studies which
guided evaluation of several nanoparticulate approaches
• Outcome: two lead formulations are in tox testing and look
promising with best tox profile of any formulation to date.
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Select Current Projects
Oncology agent for IV/oral administration use
• Issues: API has liver toxicity; Client requested development of
IV product that could be ultimately administered orally
– Home run is reduced liver tox and good oral BA
• Resolution: target nanoparticle formulation with stealth coating
• Outcome: Six formulations ready for in vitro testing.
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Select Current Projects
Taste-masking of pediatric oral Neuroblastoma agent
• Issues: API (BCS II) may have bad taste and is susceptible
to acid hydrolysis
• Resolution: evaluated several methods for taste masking
and enteric coating
• Outcome: formulations based on complex coacervation,
emulsion, and augmented drip casting methods are ready
for Client in vitro testing.
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Select Current Projects
Oncology agent for IV administration
• Issues: API is BCS II and intravenous administration is
required; Client’s original drug delivery CRO was
unresponsive, expensive, did not freely share data, and
would not supply tox batch
• Resolution: Nanocrystal approach evaluated
• Outcome: formulation at requested concentration (25%
API) developed with mean particle size of ~100 nm, with
good stability and amenable to lyophilization – evaluation
of gamma sterilization of lyophile underway.
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Select Current Projects
Cytotoxic agent for SC administration
• Issues: Client wants to match innovator IV PK profile with
SC administration. API is highly potent, BCS II, and
susceptible to hydrolysis. Client wants to incorporate
proprietary polymer into formulation.
• Resolution: nanoparticle approaches for this API including
milling in non-aqueous vehicles and production of
lyophilized material that can be reconstituted with vehicle
containing proprietary polymer
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Select Current Projects
Anti-neoplastic nanoparticle for intrathecal delivery
• Process characterization and scale up of University-
originated technology
– Develop analytic methods
– Characterize product
– Support CMC of compassionate use IND
– Produce sterile CTM