Highly Potent APIs The right platform, people and procedures for successful development and manufacturing



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Pharma&Biotech Highly Potent APIs The right platform, people and procedures for successful development and manufacturing Custom Manufacturing and Development Services for Highly Potent APIs

Pharma&Biotech Highly Potent APIs In Safe & Expert Hands Highly potent active pharmaceutical ingredients (HPAPIs) represent a significant change in the way pharmaceutical innovators are using small molecules to deliver new patient therapies. This shift toward highly potent APIs has not only led to a pipeline of more effective medicines that require lower doses and lead to fewer side effects, but also to new manufacturing challenges. With 15 years of experience and over 10 products taken from early development to late development or commercialization, Lonza understands the challenges that come with producing such high potency APIs, and we look forward to tackling them with you. Together your in-depth product knowledge and our development and manufacturing experience, technical know-how, reliable procedures, and cutting-edge facilities we can safely take your highly potent compound to the next level. For more information, or to tour our facilities, please feel free to contact one of our experts at highlypotents@lonza.com 2

Overview Chemical, microreactor, peptide, fermentation and antibody drug conjugate capabilities 15-year, multi-product track record Dedicated safety, health and environmental (SHE) experts to assess compound potency, evaluate production and monitor procedures State-of-the-art Equipment: R&D and QC laboratories, production facilities, equipment, engineering control Trusted Procedures: Maintenance, experience and training, specifically designed for handling of HPAPIs Waste management in place SafeBridge certified: Visp, Switzerland, ADC facilities, laboratory and quality control Customer Benefits Cost Reduction: A wide range of production scales, from lab scale to 10 m 3, means we can take your product from early development to launch to in-market supply without additional technology transfer costs. Time Savings: A valuable track record with scores of highly potent APIs and over 10 products scaled up, experience with a wide variety of compounds, and the right process, plants and highly trained people can minimize errors, reduce rework and improve time to market. Peace of Mind: Our cutting-edge facilities, extensive product experience, and expert evaluation and training procedures help you rest assured that your highly potent API is in safe hands. 3

Pharma&Biotech Highly Potent APIs In Safe & Expert Hands The Right Capabilities The successful and safe manufacture of high potency APIs requires a highly skilled team, the proper evaluation and training procedures, state-of-the-art facilities, and the right experience. Collectively, these attributes offer our customers a unique platform for safe and effective high potency API production. A Unique Platform Technology Complex chemistry tool box Biotechnology Backwards integration of Biopharmaceutical and Small Molecule product groups Plant Set-up Multi-purpose / product Clean-in-place set-up / decontamination Containment / Environment Biopharma Small Molecule Synergy Infrastructure Hazardous waste handling and disposal with on-site incineration Existing infrastructure Resources Handling of toxic substances cgmp experience In-house design capabilities Highly skilled personnel 4

Manufacturing Capabilities Chemical Synthesis (Visp, Switzerland) All standard chemical reactions Lab to 10 m 3 scale Target OEL 0.1 1 µg/m 3 MicroReactor Technology (Visp, Switzerland) Microbial Fermentation (Kouřim, Czech Republic and Visp, Switzerland) up to 15 m 3 Experience You Can Trust Lonza has over 110 years of chemistry know-how and an API development and production track record few contract manufacturers can match. Our experience in producing highly potent APIs goes back over 15 years. Over the past decade we ve invested $150 million to build cutting-edge facilities for highly potent API success. Today, we are able to offer a wide range of advance capabilities, from process development to large-scale manufacturing, with the potential for expansion and improvements to meet customer demand. At the heart of our high potency capabilities is our Visp, Switzerland, site. Here a dedicated high potency team is able to leverage all of Lonza s resources for highly potent API manufacturing success. Peptides (Braine, Belgium and Visp, Switzerland) Antibody Drug Conjugates (Visp, Switzerland) OEL down to 40 ng/m 3 of air Lab to 600 L scale Other Specifics Dedicated and Specialized labs in R&D and Analytical Clean room facility Air classified clean rooms 5

Pharma&Biotech Highly Potent APIs In Safe & Expert Hands Extensive Track Record Historical expertise in handling hazardous compounds Over 15 years of experience of HPAPI manufacturing at various production scales (laboratory to 10 m 3 scale) First peptide project in 2008 with Class 5 OEL Antibody drug conjugates unit with lab to plant scale experience since 2004 (OEL down to 40 ng/m 3 of air) Currently, active projects with OEL ranging from 5 to 0.04 mg/m 3 oncology immuno-suppression veterinary Production Facilities Several multi-purpose trains 250L, 630L, 2 500L, 10 m 3 target OEL 0.1 1 µg/m 3 Scale up from lab to > 500 kg per batch Hydrogenation capabilities Highly motivated and well trained operators permanent training Concept Isolators Big bags handling Dedicated clean room Cleaning in Place Cleaning based on MAC concept Validated cleaning procedures Effective cross-contamination prevention Potential Expansion Reserve (lead time 12 18 months) R&D Laboratories 4 separate labs for chemical synthesis 4 separate labs for peptides and antibody drug conjugates Lab-scale production up to 10L Class 4 and 5 (down to OEL 30 ng/m 3 ) SafeBridge certification Operating under cgmp Concept Glove box Dedicated HVAC system a1-safetech hoods Laminar flow type work benches equipped with HEPA filters enabling efficient lab work Preparatory HPLC/chromatography Lyophilization Experienced chemists with track record in scale-up and tech transfer from lab to 10 m 3 scale Dedicated, specialized training program 6

QC Laboratories 2 dedicated and fully equipped laboratories Class 4 and 5 analysis, solid handling OEL minimal 40 ng/m 3 Methods available HPLC / GC CE / icief ELISA Cell-Based Assays UV TOC Endotoxin Bioburden Osmolality Moisture by KF Turbidity Particle Testing Ion Mobility Spectroscopy / LC / MS / MS Solid state: PSD, TGA, NIR (up to Class 4) SafeBridge Certified Quality Assurance Safety Health Environment (SHE) Compliance SHE assessment made by experts in occupational hygiene and toxicology and pharmacology Extensive infrastructure for Waste Management on site SafeBridge certification (2008) Lonza classification system compared to SafeBridge Lonza Class 1 6 1 10 mg 1 mg 100 µg 10 µg 100 ng 1 ng OEL (mg, µg / m 3 ) Manufacturing Standard trains 2 R&D and QC labs Standard Hoods/Labs 3 HPAPI trains Highly Active / Potents ADC * Specialty Hoods/Labs Isolators Containment 4 5 6 Fully cgmp-certified sites Regular inspections from authorities (FDA, Swissmedic, etc.) Frequent customer audits 1 SafeBridge Categories 1 4 * antibody drug conjugate 2 3 4 7

www.lonza.com For more information, please contact: highlypotents@lonza.com North America +1 888 403 8772 Europe & Rest of World +32 87 321 687 The information contained herein is believed to be correct and corresponds to the latest state of scientific and technical knowledge. However, no warranty is made, either express or implied, regarding its accuracy or the results to be obtained from the use of such information. No statement is intended or should be construed as a recommendation to infringe any existing patent. 2010 Lonza Ltd Printed in the USA