alternative career options cros (contract research organizations) suzann hertzler, ph.d. structural...
TRANSCRIPT
Alternative Career Options
CROs(Contract Research Organizations)
SuzAnn Hertzler, Ph.D.
Structural Characterization
Catalent Pharma Solutions
12-29-09
• 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.
DISCLAIMER
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
http://www.phrma.org/publications/publications//2005-03-17.1145.pdf
New Drug Development
Time to Develop a Drug = 10 to 15 years, all aspects will involve CRO support
Drugs and Biologics approved in 2008 = 31Compounds in development in 2009 = 2,900
Development Safety Safety and Efficacy Approval Sell Drug
http://www.phrma.org/publications/publications//2005-03-17.1145.pdf
New Drug DevelopmentIND = Investigational New Drug
GLP Toxicology (Animal)Safety, Effectiveness, Dose
DRUG DISCOVERY PRE-CLINICAL CLINICAL TRAILS
Time to Develop a Drug = 10 to 15 years, all aspects will involve CRO support
Prove: identity, strength, purity, quality, potency
API Development(active pharmaceutical ingredient)
NCE/NME = New Chemical/Molecular Entity
MOI and MOA = Mode of Interest/Action
GCP: Safety and Efficacypreliminary efficacy, toxicity & pharmacokinetic information
Dose-Ranging & ADMEPharmacovigilance, Tolerability, Pharmacokinetics, & Pharmacodynamics
(Healthy)
New Drug DevelopmentNDA = New Drug Application; (BLA - Biological License)
CLINICAL TRAILS FDA REVIEWLarge-Scale Manufacturing
Phase IVPost Marketing Surveillance
GCP: Safety and Efficacy
IIA. Dosing RequirementIIB. Dose Efficacy (phase where most drugs fail)
Randomized (drug vs. placebo vs. gold std)
(Diseased)
(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
Develop Molecule
(synthesize)(clone, harvest)
In vitroIn vivoStudies
In vivoStudiesAnalytical
Pre-FormulationPre-Tox.studies, Analytical
FormulationGLP Tox. & PK Analytical
Define ToxicologyFile IND
Clinical TrialsStability Studies
EvaluateMolecule
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)
Pharmaceutical, Biotechnology Company
Outsourced to Contract Research Organizations (CROs)
• Research and Development
• Analytical Testing
• Manufacturing
• Process Development
• Toxicology studies
• Pharmacokinetics and Pharmacodynamics
• Clinical Support
• Marketing and Distribution
CRO Services*
* 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=16
390– 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
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
Catalent Pharma Solutions
Cabrillo
1999 2002
2006
Magellan
Cardinal Health
CatalentPharmaSolutions
San Diego Analytical Services •Originated as the Analytical Development Laboratory of Amylin Pharmaceuticals
Facility is 21 CFR 210 and 211 (cGMP) and 21 CFR 58 (GLP) compliant
• Formulation Development
• Analytical Development & Validation
• Structural Biomolecular Characterization
• Quality Control (QC) / Stability
with Quality Assurance (QA) oversight
Catalent San Diego Offerings
excipients, solutions, stabilizers, emulsions, powders, solubility, stability, aggregation
proof of structure, monitor modifications, support mfg, authentication, qualification
stability storage & testing, release testing, cGLP, cGMP, ICH & USP guidelines
chromatography, electrophoresis, spectrometry, & spectroscopy methods
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 & 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
Time10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 120.00 130.00 140.00
%
1
LQB-C0025-012009-2 Sm (SG, 2x3) 1: TOF MS ES+ TIC
2.47e595.80
79.83
76.10
47.83
39.51
30.6723.61
7.60 19.909.4114.56 26.10
36.84
41.28
44.33
59.59
53.98
50.44
69.14
65.44
63.12
75.14
69.89
93.40
82.38 84.96
92.33
87.57
105.37
102.23
99.32
110.48
125.82
120.36
117.12 123.53
128.51
128.95
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
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)
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: ProtocolATM: Method
SOP: standard operating procedures
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%)
• 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
Suggested Courses (online)
Q&A
Thank you for you attention
Contact Information SuzAnn Hertzler, Ph.D.Scientist, Project DirectorCatalent Pharma Solutions9240 Trade PlaceSan Diego, CA 92126(858)[email protected]
