Alkermes Contract Pharma Services specializes in solid oral dosage and sterile fill finish manufacturing, boasting over 40 years of experience and a client roster that includes seven of the world's top ten pharmaceutical companies. Their Athlone, Ireland facility is equipped to handle highly potent compounds and has the capacity to produce 2 billion solid oral dosages annually, employing rigorous safety and risk management practices. The company emphasizes operational excellence through Lean Six Sigma initiatives, ensuring compliance with global regulatory standards while addressing the challenges of high potency manufacturing.

1. © 2014 Alkermes. All rights reserved.© 2014 Alkermes. All rights reserved.
High Potency Manufacturing Capabilities
- Four Decades Providing Outsourcing Solutions to our Partners
March 2014

2. © 2014 Alkermes. All rights reserved.
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Alkermes Contract Pharma Services –
Who we are
As part of Alkermes plc, Alkermes Contract Pharma Services provides solid oral dosage
process development and manufacturing services as well as sterile fill finish capabilities
to the global pharmaceutical market.
With over 40 years in the service business, we have proven expertise in clinical and
commercial scale cGMP manufacturing of solid oral and injectable dosage forms
including high potency manufacture. We have a blue chip client list including 7 of the
world’s top 10 Pharmaceutical Companies.

3. © 2014 Alkermes. All rights reserved.© 2014 Alkermes. All rights reserved.
High Potency Manufacturing
- Facilities
- Processes
- Equipment
- Services

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4Athlone, Ireland
– solid oral dosage facility equipped to manufacture highly potent compounds
Facility on 40-acre site, FDA/EMA licensed
Formulation to scale-up to full-scale manufacturing
Multiple products manufactured and/or packaged
Global markets – supply product to 100+ markets including U.S.,
European, Asian and BRIC territories
Equipped capacity of 2 billion solid oral dosages annually
Currently manufacturing two highly potent compounds for partners
Installed capability to handle APIs to potency of 0.1µg/m3

5. © 2014 Alkermes. All rights reserved.
5Modern Facilities to Fit Your Precise Product
Requirements
Modern Solid Oral Dose Facilities in Athlone
including:
− Milling
− Screening
− Blending
− Wet granulation (high shear and fluid bed) for solvent and
aqueous processing
− Bead coating (organic solvent and aqueous based) using
Wurster FBP, CF granulation and pans
− Tableting
− Film coating and sugar coating
− Encapsulation (powder, bead, dual fill)
− Finished product packaging including cold chain
capability
− Release testing – EU QP Service available for U.S.
clients doing business in Europe

6. © 2014 Alkermes. All rights reserved.
Category 1: Low toxicity
Category 2: Intermediate toxicity
Category 3: Potent
− 3A (default)
− 3B
Category 4: Highly potent
Alkermes Compound Categorization
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7. © 2014 Alkermes. All rights reserved.
Alkermes Compound Categorization
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Understand the risks – toxicity, eco-toxicity,
process safety etc.
Use “banding” systems intelligently to deal
with early stage materials or to direct us to a
control strategy
Design and build well
Use skilled and experienced staff
Measure the effectiveness of our controls
and “verify” that our banding system actually
delivers
Apply a systematic, science-based approach
to safety
Our Approach to Managing Potent Compounds
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Category 3 Criteria*
(default category)
• High acute and chronic
systemic effects
• Irreversible effects
• High potency
• “Genic” materials and/or
sensitizers (Carcinogenic,
Mutagenic, Teratogenic,
Developmental Tox,
Reproductive Tox)
• Poor or no warning
properties
• High degree of medical
intervention required
• Immediate and delayed
onset of symptoms
• Well absorbed by mucous
membranes, via inhalation or
by the skin
* One or more of the above criteria
may place a material into this category

9. © 2014 Alkermes. All rights reserved.
Installed capability to handle APIs to potency of 0.1µg/
m3:
− At commercial high volume scale
− At development scale (discovery to phase III)
All new product introductions (NPIs) assessed and
project managed in an integrated, risk management
lifecycle approach:
− Occupational health, safety & toxicology
− Process safety
− Environmental and sustainability
− Security
Our Approach to Managing Potent Compounds
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New Product Introduction Model Safety Risk Management
– developed and executed on-site
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Closed and Contained Process for Potent
Compounds
Nova Septum
sampler – used to
removed in process
liquid samples in a
contained manner
IH monitoring
results achieved
<0.1µg/m3.
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12. © 2014 Alkermes. All rights reserved.
Products handled at commercial scale
Category Typical OELs
(µg/m3)
Types of technologies applied
1 500 • LAF booths
• LEV
• High shear granulation (aqueous and solvent)
• Bead coating (aqueous and solvent)
• Milling
• Screening
• Blending
• Tablet compression & coating
• Encapsulation
2 10-500
3a 2 • High containment dispensing, transfers & sampling
• NanoCrystal Colloidal Dispersion® (NCD) products
• Dispending, screening, fluid bed coating
• Encapsulation
3b 0.15-0.5 • Isolator, High shear granulation, blending, compression and coating
• NCD products
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Project History
Donor site capacity issue where the company was seeking an
outsourcing manufacturing partner for commercial supply
Product was classed as a highly potent compound and had an
Occupational Exposure Limit (OEL) of 0.5 µg/m3, an Adverse Drug
Event (ADE) level of 5µg/day, and exhibited teratogenic and eco-
toxic properties
The product had a low Minimum Ignition Energy (MIE) of <3mJ
Manufacturing required contained dispensing, high shear
granulation with microwave drying, blending, compression and
coating processes
Case Study: Potent API, High Volume Process
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Procedures
The following steps were undertaken to ensure containment
procedures were in place to manage the safe manufacture of the
HPAPI product:
Determination of OELs and compound categorization scheme
Industrial Hygiene (IH) exposure assessment, control verification
and sensitive IH analytical methods
Engineering controls and maintenance
General and specific handling guidance
Procedures and training
Medical surveillance
Case Study: Potent API, High Volume Process
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15. © 2014 Alkermes. All rights reserved.
The Result
The HPAPI product has been successfully tech-transferred onto
the Alkermes Athlone, Ireland site. From our involvement with
this project, a number of significant milestones were realized.
− Execution of a robust containment strategy:
− Primary: high containment primary processing areas, high containment
transfers and sampling areas were built (or established)
− Secondary: segregated processing rooms were built
− Tertiary: dedicated segregated suite, security access controlled,
Closed Circuit Television (CCTV) remote monitoring, Heating
Ventilation and Air Conditioning (HVAC) single pass air (safe change in
room), double High Efficiency Particulate Air (HEPA) exhaust, pressure
cascade and fogging shower were all put in place
Case Study: Potent API, High Volume Process
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16. © 2014 Alkermes. All rights reserved.
The Result (Continued)
− Organisation of contained and dedicated waste water facilities
− Bringing on-site Personal Protection Equipment (PPE) and Respiratory
Protection Equipment (RPE) suitable for HPAPI handling
− Establishment of segregated, high containment dust extraction systems
− Undertaking of extensive training & competence development for all staff
involved in the manufacture and handling of the highly potent product
− Establishment of medical surveillance, proactive IH & environmental
monitoring
− Enforcement of an integrated life-cycle risk management approach using a
New Product Introduction (NPI) model (Next Slide).
Case Study: Potent API, High Volume Process
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New Product Introduction (NPI) Model Safety Risk Management
– developed and executed on-site
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Success
The Highly Potent API (HPAPI) product has been successfully tech-
transferred onto the Alkermes Athlone, Ireland site
The use of the NPI model allowed for a robust approach to be
followed when bringing HPAPIs onto the site and proved effective in
implementing tech-transfers and commercial manufacture of all
products including highly potent compounds for partners
As a result of this partnership, the Alkermes Athlone site now has
the capability to handle APIs to potency of 0.1 µg/ m3 at
development (Discovery to Phase III) and commercial high volume
scale
Alkermes now successfully handles two commercially available
potent compounds on its multi-product facility in Athlone for partners.
Case Study: Potent API, High Volume Process
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19. © 2014 Alkermes. All rights reserved.
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Our Legacy of Quality
Recent successful regulatory audits from, US FDA, UK MHRA, Brazil’s ANVISA and South Korean KFDA
Exceptional compliance track record no major observations from last set of
audits, including no 483s from last US FDA audit on-site.

20. © 2014 Alkermes. All rights reserved.
Highly skilled workforce
Capability to scale-up and optimize formulation to commercial scale including
difficult to make solid oral products
On-site tech transfer to commercial manufacturing
Experience, proven track record, infrastructure and capacity in solid oral
dosage form manufacture including high potency and difficult to make
compounds
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World-Class Facilities through to Commercial Scale
Process
Optimization
Process
Scale Up
Product
Launch
Commercial
Supply
Manufacturing Services
Quality Assurance

21. © 2014 Alkermes. All rights reserved.
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Analytical Capabilities
We offer a complete range of analytical capabilities
to support CMC activities
Our highly qualified chemists and scientific staff
operate in fully equipped, best-in-class facilities that
include:
− Raw Material, In-Process and Finished Product release
testing laboratories
− Microbiology laboratories
− Bioanalytical laboratories
− Stability incubators and testing facilities
− Physiochemical characterization
− Method Development laboratories
− Method Validation laboratories
Full range of analytical technologies available
Analytical Technologies
Chromatography
• HPLC-UV, HPLC-PDA,
HPLC-RI, UPLC-UV, UPLC-
PDA
• GC-FID, GC-TCD, GC-MS
Dissolution
• Automated UV and HPLC
• Fibre Optic UV and HPLC
Characterization
• Particle Size e.g. Malvern,
Coulter, Camsizer, HIAC
• DSC and TGA
• Viscosity
Physical
• Moisture Analysis –
Volumetric and Coulimetric
• Disintegration, Hardness,
Friability
Microbiological
• Endosafe
• Vitek 2
• Rapid Micro System

22. © 2014 Alkermes. All rights reserved.
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Lean 6 Sigma/Operational Excellence Initiative
- Driving Excellence in Everything We Do
Operational Excellence (OE) Initiatives
− Trained Problem Solvers (Black Belts, Green Belts & Yellow Belts) who anticipate,
overcome and improve workflow challenges
− Value Stream Structure
− Standardized Workflows
− Process Mapping
− Improved Set-Up/Turnaround Times
− Lean Lab
− Energy Conservation
A suite of performance metrics are measured and available to you. OE Program now running for
five years.
4
black
belts
40 green belts
350 yellow belts
Strategic OE Staff Training Plan

23. © 2014 Alkermes. All rights reserved.
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Our Collaborative Approach
– Our Promise to You
Experience and Expertise
• 45 years providing contracting services to our partners
Exceptional Compliance Track Record
• Successful audits from all regulatory agencies including US
FDA, EMA, Anvisa, Japanese regulatory agency
Compliant, Reliable and Cost Efficient Supplier
• Embedded Operational Excellence and Lean 6 Sigma
• Established Key Performance Metrics (KPIs) tracking product
performance
World Class Modern Facility
• Established record in solid oral dosage manufacturing
• Experience in high potency manufacturing
• Located in low tax jurisdiction (LSJ)
Committed to your manufacturing needs
• Long term commitment to manufacturing your outsourcing
requirements
45 years experience and
expertise manufacturing and
developing products for our
partners

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Contact Us
Alkermes Contract Pharma Services
Monksland
Athlone
Co Westmeath
Ireland
Fidelma Callanan
Snr Director Commercial Development
Fidelma.Callanan@alkermes.com
Phone: +353 9064 95126
Website: www.alkermes.com/contract