Leader in Sterile Contract Manufacturing

• Mission Statement

• Corporate Vision

• Corporate Focus

• Aseptic Filling Capabilities

• Current Floor Plan

• Syringe Filling CapabilitiesInova H3-5VInova SV-122

• Vial Filling CapabilitiesInova VFVM-3031

• Lyophilization

Capabilities

• Regulatory

Compliance

• Analytical

Capabilities

• Organizational Chart

• Continued Growth

• Future Facility

Planning

• Working With You

The mission of Hyaluron Contract Manufacturing is to be aleader in aseptic contract manufacturing of parenteral products.

We are committed to quality, innovation, continuous improvementand regulatory compliance.

HCM takes pride in meeting the unique needs of each client.

HCM values each employee and provides a supportive work environment with opportunity for growth.

Mission Statement

Corporate Vision

• Leader in high quality aseptic contract

manufacturing

• Apply creativity and innovation in solving client manufacturing challenges

• Committed to quality, continuous improvement,

regulatory compliance, on time delivery and responsiveness

• Value performance, employee satisfaction, a

supportive work environment, and opportunity for growth

Corporate Focus• Sterile formulation and filling

Pre clinicalClinicalCommercial

• Expertise in Gels Viscous products Suspensions Homogenization Diafiltration

• Hyaluronate products Viscous biopolymer Proprietary sterilization method

• Three aseptic fill suites

• CapabilitiesInova SV122Semi-automatic syringe filler(50,000 units/day)

Inova H3-5VFive head on-line vacuum fill/stoppering syringe filler(100,000 units/day)

Inova VFVM3031Only vial filler in the North East offering class100 capping(75,000 units/day)

Aseptic Filling Capabilities

Inova H3-5V

• First of its kind in the USA

• Online vacuum filling and stoppering, for viscous products and air sensitive compounds

• Fills up to 100,000 syringes per day

• Bubble-free fillingTM

Syringe Filling

SV-122

• Online stoppering

• Offline vacuum stoppering

• Validated 0.5mL long – 20mL syringe

sizes

• Up to 50,000 syringes/day

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Syringe Stoppering Options

• Bubble-free filling™ technology allows for the filling of products with no gas bubbles

• Bubble-free filling ™ may increase stability when:

Dissolved oxygen negatively impacts stabilityof drug solution

Gas-liquid interface causes molecularrearrangements (i.e. proteins)

Bubbles, in conjunction with silicon,cause aggregation (i.e. proteins)

• Bubble-free filling™ increases sterility assurance / microbiological safety by:

Preventing stopper movement during shipping (reduced

pressure)

Inhibiting growth of some microorganisms

Bubble-free fillingTM

Syringe Stoppering Options

• Traditional Online Stoppering

• Offline Vacuum Box Stoppering

• Online Vacuum Filling and Stoppering

• No operator interaction needed• Headspace depth setting• Speed• Relatively simple equipment• Air can be replaced with inert gas(es)• Aids in manual mixing of suspension products

• Removes almost all air / gas• Replaces 99.9% of the remaining air with inert gas• Was stoppering method of choice for viscous products• Compatible with coated stoppers• No operator interaction needed• Ensures reproducible delivered dose• No gas bubble• Vacuum filling helps de-gas the liquid• Prevents some microorganisms from growing• Compatible with coated stoppers

Inova VFVM 3031

• Class 100 Area Capping

• Low Hold Up Volumes

• Single Star-wheel

• Suction Stopper Placement

• 1.0mL – 100mL vial sizes

• Up to 75,000 units/day

• Validation Completed – 1/06

Vial Filling

Lyophilization – BOC Edwards Lyo-Max 3

• cGMP Construction

• Part 11 Compliant Control Software System

• Lyomaster PC Control System

• 316L Electropolished Stainless Steel Chamber

• 36 sq. ft. total shelf area (six adjustable shelves)

• Pure Steam Sterilization Capability

• CIP (clean-in-place) Capability

• Integrated Sterile Filter Integrity test for Sterile Vent Filters

Stability Optimization Service (SOS)

• Stability data comparison

• Variety of containers

• Variety of temperature points

• Full cGMP laboratory support

Regulations

• 21 CFR Part 211 (Drugs)

• 21 CFR Part 820 (Quality System Regs)

• 21 CFR Part 600 (Biologics)

• ISO 9001:2000/13485:2003

• QP Inspected- Approved for clinical supply

into Europe for Phase 1 – Phase 3

• FDA inspected for Drug and Medical Device

Analytical Capabilities• Waters HPLC, with UV and RI Detectors• Thermo Focus GC/Tri-Plus Auto- Sampler/FID, Liquid Sample and Head Space• Thermo Nicolet Avitar 370 FTIR• Pheonix 8000 TOC Analyzer• Beckman DU UV/Visible • AquaStar Coulometric Karl Fischer• Advanced Instruments Osmometer• AR-1000 Rheometer• Brookfield HADV-II+ Viscometer• Brookfield LVDV-E Viscometer

• Ubbelohde L50, L100, L350 Viscometer• pH Meter• Consistometry Measurement• Conductivity Measurement• Pyrogen/LAL/Endotoxin Tests• Bioburden Tests• Growth Promotion Tests• ELSD800 Light Scattering Detector• NiComp380 ZLS Particle Sizer• Gel Electrophoresis

A. Confidentiality AgreementB. Product SurveyC. QuoteD. ContractE. Start Project

I. “Kick-Off Meeting”II. Batch Record (~2-3wks)III Engineering Run (~2wks)IV. Validations (~4wks)

IVa FormulationIVb MixingIVc SterilizationIVd Other

Hyaluron- Working With You

V. Material Release/Component Prep.

VI. Aseptic Fill [Lyo/Aseptic Capping] (~1wk)

VII. Inspect, Label, Test, Package (~1wk)

VIII.Ship (Released [n/a] or Quarantined)

IX. Batch Record Review/Release (5wks)

Thank you for your interest in HCM!