Presentation of Capabilities

Capabilities

Penn Pharma’s Core Competencies include:

• Formulation Development

• Analytical Services

• Clinical Trial Supply

• Commercial Manufacturing

• Packaging & Labeling

• Logistics

• Contract Manufacture and Packaging

• CMC and QP Consulting

Capabilities

Formulate, test & manufacture pharmaceutical products for clinical or commercial useTabletsCapsules LiquidsOintments/creamsSuppositoriesGranules

Pack, store & distribute ALL forms of pharmaceutical products for clinical and commercial use Import & release pharmaceutical products into the EU

Bldg 23

Bldg 24

‘Border’

Facilities

Penn operates from a primary site of three hectares (323,000sq.ft.) in Tredegar and a new (75,000sq.ft.) storage facility in Oakdale, South Wales. (2.5 hours west of London)

Custom Manufacture and Packing

16 class 100,000 GMP rooms

Low humidity suites

One pot processing for

blending, granulating and

drying

Packing facilities

Contained ManufactureDedicated Containment Facility (DCF)

• Fully contained Suiteo Handling of teratogenic compounds

Contained ManufactureSmall Scale HCO Operations

Operation• Since January 2008

Containment Room• class 100,000 • negative pressure• double airlock• single-pass HVAC• safe-change EU 13 HEPA filters

Validation• airborne containment by Lactose handling

trials

Standards• conforms to ISO Class 8 (100,000); BS EN

ISO 14644-1 (1999) & EU GMP volume IV

Closed manufacturing system

• Isolator stage for dispensing highly potent API

• ChargePoint valves for contained transfer of API (powder

or solution) to a Zanchetta P10 one-pot high-shear

mixer/granulator/dryer, or dry blender.

• Contained transfers to milling & final blending stages

• Contained transfer to tablet press, or capsule filler

• Batch sizes currently ~ 3.5kg (wet) or 6.0kg (dry)

• Process validated to OEL >1<10mcg/m3, OEB 4

(occupational exposure band)

• In addition operators can wear positive pressure air suits

(if necessary according to risk assessment)

Contained ManufactureSmall Scale HCO Operations

We offer a complete range of Formulation Development Services including:• Pre-formulation studies.• Formulation of a wide variety of dosage forms.• Formulation and manufacture of batches for stability testing.• Scale up and production of pilot batches.• Formulation of clinical trials supplies from Phase l through to Phase lV.• Process validation and technology transfer.

The dosage forms on which we work include:• Solid Dose: Tablets, hard gelatin capsules, granules and powders.• Liquids: Oral and topical liquids, suspensions and emulsions. • Semi-solids: Creams, ointments and gels.• Parenterals

The types of dosage form technologies that we are familiar with include:-• Immediate release matrices• Sustained and controlled release formats.• Hot melt filling of capsules.• Film coating (particles and tablets).• Melt granulation

Formulation Development

We have particular specialist expertise in formulating for poorly water soluble drugs using a range of non-proprietary solubility enhancement techniques.Advances in combinatorial chemistry and high throughput screening techniques are producing more drug candidates with greater specificity towards biological targets. However, a great many of the compounds now coming through the development pipelines are Class II drugs according to the BCS classification, which means they exhibit good permeability through biological membranes, are lipophilic and, hence, poorly water soluble. There are often problems associated with oral administration of this category of drug due to the limited solubility in the aqueous environment within the gastrointestinal tract. The prime objective for Penn’s formulation scientists is to improve the water solubility of these drugs for our clients.

Analytical Services

35 Station Lab• 32 HPLC’s

o 1 UPLC with UV, RI, EC & ELSD detection• 2 GC headspace systems• Waters LCMS• 2 containment labs (teratogenic/cytotoxic)• Dark room facility• Full dissolution capabilities• Full range of ICH stability storage including photo-stability

Stability Volumes• ICH light cabinet (refrigerated), 0.2m3• 2-8°c, 3.3m3• 25/60, 18m3• 30/60, 1.2m3• 30/65, 2.4m3• 40/75, 2.0m3

Clinical Trial Manufacture

Part of Penn’s Formulation Development Team

Scalabilityo Direct scalability for one pot

processing from 300g batch size to >300kg scale

o Mi-Pro mini scale equipment allows early process development using gram quantities of API

Capabilities same as Contract Manufacture

Clinical Trial Supplies

Packaging & LabellingInvestigational Initiated StudiesCommercial Product Sourcing for Clinical TrialsFastTrack CTS

Dedicated team for early phase and Phase I clinical trial projects Seamless, integrated approach in line with Penn's other services Each team member is experienced in protocol interpretation to the dispatch of supplies to investigator site No transfer project between departments or groups which reduces miscommunication and loss of valuable time. Simplicity of documentation reduces the amount of paperwork created but procedures still remains regulatory compliant Many projects are completed within a 3 week period or less

Product Sourcing for CTS

• Comparators• Rescue Medications• Non-Investigational Medicinal

Products• Investigational Medicinal Product

Penn sources from the most appropriate source and ensures QP input, assuring supply chain integrity.

Understanding the difference between these categories and ensuring supply chain integrity is critical for any clinical trial. Many “comparator sourcing” companies do not understand the importance of these issues.

LogisticsTemperature Controlled Warehousing

• Ambiento 2,650 pallet locations

• Refrigeratedo 200m3

• Frozen (-20°c)o 32m3

• Controlled drugso 22m3

• Serge demand secure @o Movianto, Bedford, UK

2-8°c, -20°c, Ambient & CD

o Biotec, Wales -20°c & -80°c

QP Services / Consulting• Five-strong team of QPs

• Diverse experience covering all dosage forms

• Certify both IMP and licensed products

• Undertake familiarisation audits of non-EU facilities

• Large portfolio of audited manufacturing sites

• Support EU Pharmaceutical Portal Service

• Advise on all aspects of CMC

o API to commercial products

• IMPD Review and Advice

• Online CMC consultancy service

• Hosting various regulatory authority inspections

o MHRA, FDA, ANVISA

Why Penn Pharma?Penn Pharma provides an unparalleled suite of pharmaceutical development, clinical trial supply and manufacturing capabilities. Our flexible and personal approach ensures our clients are listened to and we offer cost effective and time saving solutions. Due to the volume and varied nature of the projects and the wide variety of clients we work with, our depth of knowledge and breadth of experience is unmatched.

Penn Pharma provides a suite of drug development, clinical trial supply, manufacturing and consultancy services. Our core services include formulation development, analytical development, clinical trial manufacture, packing, labeling, storage and distribution, returns reconciliation and destruction, custom manufacture, specials manufacture, hi-potency capabilities and CMC and QP release consultancy services.

Contact UsHead Office:Penn Pharma, 23-24 Tafarnaubach Industrial Estate, Tredegar, Gwent, NP22 3AA, UKMain Telephone: +44 (0) 1495 711 222www.pennpharm.com

Michael Kruidenier, Business Development ManagerTel: +44 (0) 1495 713 650Mobile: +44 (0) 7791 751302Email: michael.kruidenier@pennpharm.com