Alternative Career Options CROs (Contract Research Organizations) SuzAnn Hertzler, Ph.D. Structural Characterization Catalent Pharma Solutions 12-29-09

DISCLAIMER The views reflected in this presentation are solely those of the presenter and do not necessarily reflect the position of my company, any of its clients, or any of my friends and colleagues that contributed to the presentation.

Overview Overview of the drug development process Importance of CROs to drug development Catalent Pharma Solutions overview Catalent San Diego services overview Catalent Structural (biomolecular) services My roles as a Scientist and Project Director

New Drug Development Development Safety Safety and Efficacy Approval Sell Drug http://www.phrma.org/publications/publications//2005-03-17.1145.pdf Time to Develop a Drug = 10 to 15 years, all aspects will involve CRO support Drugs and Biologics approved in 2008 = 31 Compounds in development in 2009 = 2,900

New Drug Development DRUG DISCOVERY PRE-CLINICAL CLINICAL TRAILS IND = Investigational New Drug DRUG DISCOVERY PRE-CLINICAL CLINICAL TRAILS MOI and MOA = Mode of Interest/Action API Development (active pharmaceutical ingredient) preliminary efficacy, toxicity & pharmacokinetic information GCP: Safety and Efficacy GLP Toxicology (Animal) Safety, Effectiveness, Dose (Healthy) Dose-Ranging & ADME Pharmacovigilance, Tolerability, Pharmacokinetics, & Pharmacodynamics Prove: identity, strength, purity, quality, potency NCE/NME = New Chemical/Molecular Entity http://www.phrma.org/publications/publications//2005-03-17.1145.pdf Time to Develop a Drug = 10 to 15 years, all aspects will involve CRO support

New Drug Development CLINICAL TRAILS FDA REVIEW NDA = New Drug Application; (BLA - Biological License) Large-Scale Manufacturing CLINICAL TRAILS FDA REVIEW GCP: Safety and Efficacy Phase IV Post Marketing Surveillance Randomized (drug vs. placebo vs. gold std) (Diseased) IIA. Dosing Requirement IIB. Dose Efficacy (phase where most drugs fail) (Healthy and Diseased)

Key Acronyms CRO, CMO: Contract Research (Manufacturing) Organization MOI, MOA: Mode of Interest, Most of Action NCE, NME: New Chemical Entity, New Molecular Entity API: Active Pharmaceutical Ingredient DS: Drug Substance (API plus inactive ingredients of formulation) DP: Drug Product: Finished Dose Form (all ingredients, solvents, fillers, containers, closures, packaging, and labeling) IND: Investigational New Drug NDA (BLA): New Drug (Bioloigic License) Application cGXPs: current good practices according to FDA CFRs GLP: laboratory (tox. and animal studies); GMP: manufacturing (CMC, analytical testing); GCP: clinical trials ADME: Absorption, Distribution, Metabolism, Excretion

Importance of CROs CROs are integral to the drug development process Molecule (synthesize) (clone, harvest) In vitro In vivo Studies In vivo Studies Analytical Pre-Formulation Pre-Tox.studies, Analytical Formulation GLP Tox. & PK Analytical Define Toxicology File IND Clinical Trials Stability Studies Evaluate Molecule 50 mg - 2g (1L biologic) 2 – 25 g (10L biologic) 100 – 400 g (50L biologic) 1 – 10 kg (200L biologic) 10 - 500 kg (2,000L biologic) Outsourced to Contract Research Organizations (CROs) Pharmaceutical, Biotechnology Company

CRO Services* Research and Development Analytical Testing Manufacturing Process Development Toxicology studies Pharmacokinetics and Pharmacodynamics Clinical Support Marketing and Distribution * Not an extensive list of support

CROs in Massachusetts* http://www.blueskybiotech.com/ http://www.abtassociates.com/index.cfm http://www.apredica.com/ http://www.asischem.com/ http://www.biotrofix.com/ http://www.gwathmey.com/ http://www.idexx.com/view/xhtml/en_us/preclinical-research.jsf?conversationId=16390 http://neuromorphometrics.com/ http://www.phylonix.com/ http://www.wolfelabs.com/ http://www.xtalbiostructures.com/ http://www.criver.com/en-US/Pages/home.aspx http://www.synomicspharma.com/ http://www.gvkbio.com/ http://www.averionintl.com/ * Not an extensive list. There are many with a range of support services

Catalent Pharma Solutions Employs approximately 10,000 at more than 30 facilities worldwide Drug Delivery Systems (oral, inhaled, sterile) Manufacturing (oral dose and sterile) Packaging (contract, printed, specialty) Development (biopharm, product, clinical supply) Biopharm: Gene exp, Bio Mfg, Analytical, Biosafety, Bioassay,

Catalent Pharma Solutions San Diego Analytical Services Originated as the Analytical Development Laboratory of Amylin Pharmaceuticals Cabrillo 1999 2002 2006 Magellan Cardinal Health Catalent Pharma Solutions Facility is 21 CFR 210 and 211 (cGMP) and 21 CFR 58 (GLP) compliant

Catalent San Diego Offerings Formulation Development Analytical Development & Validation Structural Biomolecular Characterization Quality Control (QC) / Stability with Quality Assurance (QA) oversight excipients, solutions, stabilizers, emulsions, powders, solubility, stability, aggregation chromatography, electrophoresis, spectrometry, & spectroscopy methods proof of structure, monitor modifications, support mfg, authentication, qualification stability storage & testing, release testing, cGLP, cGMP, ICH & USP guidelines

Catalent San Diego Offerings API, DS, DP Characterization & Quality Every Lot (phase 0 to phase IV) prove: Identity, Purity, Potency, Strength, Safety IDENTITY: NMR, MS, IR, WB, characterization assays, appearance PURITY: RP, SEC, SDS-PAGE, SDS-CGE, CZE, IEF, LC-MS, GC-MS, MP, KF, Particles POTENCY: activity assays, concentration, ELISA SAFETY: Bioburden, Endotoxin, Particulate, Sterility, Residuals *Assays will vary by compound & client

Structural Characterization Services Structural characterization & analysis of proteins, peptides, small molecules and oligonucleotides Glycosylation analysis (Quantitative Monosaccharide and Sialic acid analysis, Oligosaccharide profiling, Glycoprofiling including site occupancy by LC-MS)

Structural Characterization Services Peptide Mapping, Disulfide Bond Mapping, Analysis of PTM’s, and Intact Molecular Weight by LC-MS Small molecule elemental composition and impurity analysis by LC-MS and GC-MS

Structural Characterization Services Capillary Electrophoresis (cIEF, SDS-CGE, CZE), Circular Dichroism, Amino Acid Analysis, Extinction Coefficient Determination, and N-terminal Sequencing Method Development and Validation

Catalent Project Work Flow Write TTP/ATM Sample Receipt & Tracking Paper & Electronic Archival Write Technical Report QA Audit Testing & Analysis Direct Analyst Request Notebooks (TTP, ATM, Phase) Data Review Compare, Critic Results Report sent to Customer Generate Quotes Customer Signature Write SOPS TTP: Protocol ATM: Method SOP: standard operating procedures Administrative Responsibilities of a Project Director: Monthly Responsibilities: Client Deadlines (Lot Release, Stability, IND, NDA) Catalent Financial Goals Approve Analyst Work Hours Monitor Analyst Efficiency (time = money)

Project Director/Manager Point of Contact for the Client Participate in project planning, decision-making, developing implementation strategies, and leading efforts for projects (quoting prices for services; writing protocols, methods, SOPs, and analysis reports) Work with team to create & maintain project plans and timelines Direct analyst to deliver projects on track & on budget Direct OOS or Aberrant Data Investigations Responsibilities: Project director (~ 40%), Analytical lab work (~ 60%)

Suggested Courses (online) UCSD Extension Program Regulatory Affairs Essentials (6 courses) Regulatory Requirements for Drugs & Biologics Regulatory Compliance for Drugs & Biologics Good Clinical Practices Good Laboratory Practices Good Manufacturing Practices Overview of Regulatory Affairs for Medical Devices Biotech & Pharmaceutical Manufacturing courses Drug Discovery & Development Courses www.fda.gov/cder or /cber or /chrh

Thank you for you attention Q&A Thank you for you attention Contact Information SuzAnn Hertzler, Ph.D. Scientist, Project Director Catalent Pharma Solutions 9240 Trade Place San Diego, CA 92126 (858)547-7907 suzann.hertzler@catalent.com