20 Pacific DriveQuakertown, PA 18951

Tel: 215-536-5605 • Fax 215-536-6630www.powdersize.com • sales@powdersize.com

COMPANY HISTORY

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FACILITY OVERVIEW

Established in 1993, Powdersize, Inc. is a privately held company with the vision to “set the benchmark” within thepharmaceutical contract manufacturing marketplace. Within the first year of operation, the plant was registered and approvedby the FDA to process pharmaceutical drug substances and food grade materials. Routine FDA audits have resulted in anexemplary record of regulatory compliance. This in turn, provides our clients with confidence that the purity, identity, andstrength of their pharmaceutical powders will be maintained during cGMP processing. Over the years, our micronizationcapacity has been expanded to include the ability to process gram and kilogram (pilot) level scales for R&D and clinical trialsrespectively. Commercial scale processing capability and the qualification of containment isolators to process high potencyAPIs (HP-APIs) have been added to keep pace with the growing industry demand for our services.

Production Suites:The Powdersize facility offers 6 commercial suites and 1 clinical/pilot scale suite of cGMP design featuring:

• Segregated Processing Suites

• Dedicated HVAC Systems

• HEPA Filtration

• Positive Pressure Airlocks/Gowning Rooms

• Availability of R&D, Clinical or CommercialScale Equipment Trains

• Capabilities to Facilitate either Continuous orBatch Mode Processing

Quality Control Laboratory:A fully equipped Quality Control Laboratory is maintained on site to perform particle size analyses on all in-process and finishedproduct release samples via laser diffraction or US mesh sieve fractionation. Additionally, analytical instrumentation such asHPLC and TOC are available to measure product residual levels associated with validated cleaning methods.

TYPICAL DEVELOPMENTAL PATH

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Material Evaluation:A small sample will be requested to evaluate the starting particle size distribution and physical properties such as friability,hardness and feedability. The safety of the compound in terms of toxicity, occupational exposure limits (OELs), and explosivityis also evaluated.

A non-GMP trial is recommended to provide a low cost, immediate turn-around processing event in which a “proof of

concept” sample will be returned to the client to evaluate the benefit of the milling, micronization or classification servicedeveloped for the client’s application. Additional outcomes of a non-GMP trial will be estimations of throughput, cost andprocess parameters required for commerical scale cGMP processing.

A GMP production event will require cGMP documentation to be drafted and approved prior to a production campaign.

The documentation will include a Customer Standard Batch Procedure (CSBP) to document the necessary client, Powdersize, Inc.and cGMP processing requirements. Additionally, analytical method(s) are transferred to Powdersize, Inc. for use in post-runcleaning verification.

Safety & Feasibility

Evaluation

NonGMP

Trial

Gram Scale or

KG Scale

MSDS Material Sample(gram level)

CleaningValidation

CustomerStandard Batch

Procedure

GMP

Production

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Capabilities:• Micronization (jet milling) • Vibratory, Ultrasonic and Air Swept Screening • Mechanical Milling • Air Classification• Isolator Containment for Processing Highly Potent Compounds

cGMP Markets Served:• Pharmaceutical APIs & Excipients • Nutraceuticals • FDA Approved Food Grade Powders• DEA Controlled Substances

Processing Scales Available:• R&D Scale---starting at 5-10 grams • Clinical/Pilot Scale---starting at 1 kilogram • Commercial Scale---starting at 400 kilogram

Particle size is an important characteristic for many

dosage forms. Stability, flowability, dissolution rate

and bioavailability are among the parameters

affected by the size distribution of particles.

Applications of Micronization:

• Generate particles fine enough to be properly delivered to the lungs (for inhalation product development).

• Enhance bioavailability of oral drugs across the intestinal epithelium (in the development of tablets and capsules).

• Help enhance absorption of a drug across the skin (in the development of transdermal products).

• Help with solubilizing poorly soluble compounds as in the development of emulsions and suspensions or microparticulatesystems.

• Speed the dissolution rate of a drug. Enhance flow characteristics of powders.

• Enhance wetting properties to improve solubility. Improve drug stability and the taste properties of a compound.

THE IMPORTANCE OF MICRONIZATION

CAPABILITY OVERVIEW

QUALITY POLICY

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• We strive to provide the highest quality contract particle size reduction and/or classification services to thepharmaceutical, food and medical device marketplaces.

• This will be achieved by the application of a sound Quality Management System and compliance with current GoodManufacturing Practices as defined by 21CFR part 210/211 and ICH Q7 Guidance for Pharmaceutical API manufacture.

• While doing so we shall keep in mind the safety of our employees, all work processes, as well as our natural environment.

• The company shall develop robust manufacturing processes that provide products of consistent particle size which aresafe for use in applications which require human consumption or treatment of disease.

• Human resources are one of our biggest assets. Our qualified and trained staff is provided continual training to upgradetheir knowledge and stay conversant with state of art technology.

• The company will actively evaluate and reward personnel for continuous improvement efforts that strengthen the qualitycontrol & assurance functions that are critical to our success.

• It is the obligation of the company to share in the responsibility of quality assurance by keeping vigil while purchasing,maintaining, manufacturing, testing, and the distribution of our clients’ products.

• The company shall make available all the requisite measures and resources to achieve the above goals.

Validation

SOPReview

QualitySystems

QualityReview

CAPA

BatchRecordAudits

AnalyticalMethod

Development

CleaningVerification

OutgoingQC

Inspections

InternalAudit

PestControl

IOQVendorApproval

EmployeeTraining

LabelTracking/Accounting

IncomingQC

Inspections

Calibration

QUALITY SYSTEMS

A robust set of quality systems are in place to comply with regulations defined in 21 CFR part 210/211 and the expectationsdescribed in ICH’s Q7 Guidance for API manufacturing. Continuous dialog with FDA, clients’ quality assurance personnel andvarious industry associations allow Powdersize, Inc. to benchmark internal quality systems against current thinking to continuallyreduce patient risk.

TECHNOLOGY OVERVIEW

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Particle Size ReductionJet Milling: Material is fed into a grinding chamber where particles are accelerated via compressedgas to create a tornado-like flow path. Large particles migrate to the outside of the mill via centrifugalforce where particle attrition occurs over time from continuous particle collisions and inner-particleabrasion. Micronized particles migrate to the center of the mill via drag force pulled at the milloutlet. Mill pressure, feed rate, grinding chamber design and feed angle can be varied to influencethe size of the particles created.

Pin Milling: Material is fed into a grinding chamber where a spinning disk with varying sized pinscreates a torturous flow path. Particles are directly impacted by the pins and sheered against fixedchamber surfaces leading to size reduction. The size of the screen mesh at the mill outlet, rotationalspeed of pin disk and design of the pin disk can be varied to influence the size of the particles created.

Hammer Milling: Material is fed into a grinding chamber where a series of spinning blades impactparticles creating sheer against fixed chamber surfaces and/or direct particle fracture leading to sizereduction. The size of the screen mesh at the mill outlet, rotational speed of blades and blade designcan be varied to influence the size of the particles created.

Powder ClassificationPneumatic Screen Classification: Material is conveyed and presented pneumatically to ascreen of certain mesh size. Oversize particles are physically blocked from passing through thescreen and are directed to an oversize chute for collection. Particles below the mesh size of the screenpass through the screen and are conveyed to a product collector. Screens are continually swept witha rotating wand utilizing high pressure air to clean the screen and maintain high separationefficiencies between oversize and fine particles. Mesh size of classification screens can be varied toinfluence the particle size cut required.

Vibratory Screen Classification: Material is fed to the center of a horizontal circular screenor stack of screens. The screen(s) vibrate about their center of mass, accomplished by eccentricweights on the upper and lower ends of the motion-generator shaft. Rotation of the top weight createsvibration in the horizontal plane, which causes material to move across the screen cloth to theperiphery. The lower weight acts to tilt the machine, causing vibration in the vertical and tangentialplanes. The lead angle of the lower weight in relation to the upper weight provides variable controlof the spiral screening pattern. Speed and spiral travel pattern of the material over the screen cloth

can be set by the operator to achieve maximum throughput and screening efficiency. Ultrasonic modulators can be added toscreens to further improve screen efficiencies with fine powders.

Air Classification: Material is fed into a classification chamber where powder is de-agglomeratedand classified through centrifugal force created by a classifier wheel. Fines are separated fromoversize via rotational speed of the spinning classifier wheel and an exit gate setting. Feed rate, airflow and rotor speed can be adjusted to vary the “cut size” of the fractions.

High Potency Containment

High Potency (HP-API) Milling: Various mechanical and jet milling capabilities describedabove are available within an isolator designed to meet containment levels down to Category 4OEL limits as defined by Safebridge. The isolator provides a negative pressure Nitrogenenvironment, double HEPA filtration, RTP transfer ports, CIP capability and the ability to processgram to 100 KG quantities.

20 Pacific DriveQuakertown, PA 18951

Tel: 215-536-5605 • Fax 215-536-6630www.powdersize.com • sales@powdersize.com