Transcript Alternative Career Options

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
IND = Investigational New Drug
DRUG DISCOVERY
PRE-CLINICAL
MOI and MOA = Mode of Interest/Action
API Development
(active pharmaceutical ingredient)
preliminary efficacy, toxicity &
pharmacokinetic information
CLINICAL TRAILS
GCP: Safety and Efficacy
GLP Toxicology (Animal)
Safety, Effectiveness, Dose
NCE/NME = New Chemical/Molecular Entity
Prove: identity, strength, purity,
quality, potency
(Healthy)
Dose-Ranging & ADME
Pharmacovigilance, Tolerability,
Pharmacokinetics, &
Pharmacodynamics
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
NDA = New Drug Application; (BLA - Biological License)
Large-Scale
FDA REVIEW
Manufacturing
CLINICAL TRAILS
GCP: Safety and Efficacy
Phase IV
Post Marketing Surveillance
(Diseased)
Randomized
(drug vs. placebo
vs. gold std)
IIA. Dosing Requirement
IIB. Dose Efficacy (phase where most drugs fail)
(Healthy and Diseased)
Key Acronyms
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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 vitro
In vivo
Studies
In vivo
Studies
Analytical
Pre-Formulation Formulation
Pre-Tox.studies, GLP Tox. & PK
Analytical
Analytical
Define
Toxicology
File IND
Clinical Trials
Stability Studies
Evaluate
Molecule
50 mg - 2g
(1L biologic)
Pharmaceutical,
Biotechnology Company
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)
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*
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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/preclinicalresearch.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
Magellan
1999
Cardinal Catalent
Health
Pharma
Solutions
Facility is 21 CFR 210 and 211 (cGMP) and
21 CFR 58 (GLP) compliant
Catalent San Diego Offerings
• Formulation Development
excipients, solutions, stabilizers, emulsions, powders, solubility, stability, aggregation
• Analytical Development & Validation
chromatography, electrophoresis, spectrometry, & spectroscopy methods
• Structural Biomolecular Characterization
proof of structure, monitor modifications, support mfg, authentication, qualification
• Quality Control (QC) / Stability
stability storage & testing, release testing, cGLP, cGMP, ICH & USP guidelines
with Quality Assurance (QA) oversight
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
POTENCY: activity
assays, concentration,
ELISA
PURITY: RP, SEC, SDS-PAGE,
SDS-CGE, CZE, IEF, LC-MS,
GC-MS, MP, KF, Particles
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
LQB-C0025-012009-2 Sm (SG, 2x3)
1: TOF MS ES+
TIC
2.47e5
95.80
105.37
110.48
79.83
76.10
47.83
102.23
93.40
%
82.38 84.96
59.59
125.82
99.32
69.14 75.14
53.98
120.36
128.51
128.95
92.33
39.51
41.28
65.44
87.57
117.12
44.33
30.67
23.61
7.60 9.41
14.56
19.90
36.84
50.44
63.12
123.53
69.89
26.10
1
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Structural
Characterization Services
AMINO ACID ANALYSIS RESULTS REPORT
Project Name CPS_C0016_Validation
S AMP L E
INF O R MAT IO N
•Capillary Electrophoresis (cIEF, SDS-CGE, CZE),
Circular Dichroism, Amino Acid Analysis, Extinction
Coefficient Determination, and N-terminal Sequencing
Sample Name:
Sample Type:
Vial:
Injection #:
Injection Volume:
Run Time:
Sample Set Name:
Cal Std
Unknow n
21
1
50.00 ul
77.0 Minutes
070203_EDE1
Acquired By:
Date Acquired:
Acq. Method Set:
Date Processed:
Processing Method:
Channel Name:
Proc. Chnl. Descr.:
edenton
7/3/2003 12:21:14 AM
AAA Pickering method at 50 C
7/15/2003 12:59:13 PM
AAA Pickering Method at 50 C b
SUM_2487
[2487Channel 1] + 2487Channel 2
•Method Development and Validation
Histidine
Lysine
Tryptophan
0.05
Arginine
Glycine
Alanine
Proline
0.10
Aspartic Acid
Threonine
Serine
Glutamic Acid
AU
0.15
Cysteic Acid
0.20
Valine Cystine
Methionine
Isoleucine
Leucine
Norleucine
Tyrosine
Phenylalanine
Auto-Scaled Chrom atogram
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40.00
Minutes
50.00
60.00
70.00
Catalent Project Work Flow
Administrative
Responsibilities of a
Project Director: Paper &
Customer
Signature
Generate
Quotes
Electronic
Archival
Report sent
to Customer
Write Technical
Report
Write
TTP/ATM
Write SOPS
SOP: standard operating procedures
Sample Receipt
& Tracking
QA Audit
Monthly Responsibilities:
•Client Deadlines
(Lot Release, Stability, IND, NDA)
Data
Review
Compare, Critic
Results
•Catalent Financial Goals
•Approve Analyst Work Hours
•Monitor Analyst Efficiency (time = money)
Request Notebooks
Testing &
Analysis
Direct Analyst
TTP: Protocol
ATM: Method
(TTP, ATM, Phase)
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
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
[email protected]