The Investigational Drug Program: A
for-profit organisation operating under
the umbrella of the BC Cancer Agency,
a Governmental non-profit organisation
Dawn N. Waterhouse, PhD, MBA
To Profit or Not to Profit
That is the question
A Brief History - IDP
• The Investigational Drug Program was established
in 1995 with initial funding and loans by the BC
Ministry of Special Programs and Western
Economic Diversification. The cost of building the
infrastructure was minimal, approximately $350K
• Maximum capacity reached by 1997
• 96 successful parenteral batches to date
• Animal models
• Integration
Mandate
To expedite the development of
promising new therapeutic agents
to the stage where they can be tested
in Phase I and II clinical trials
A For Profit Unit of an NPO
• Non-profit
– Organisation operated for social welfare etc.
– No income may be used for personal benefit (aka “I don’t get a
bonus”)
– 40% of revenues must be government funding
• Profitable unit
– Under the Income Tax Act of Canada, non-profit organisations and
public foundations are permitted to engage in related businesses
that accomplish or promote their goals.
• collection of money in BCCA parkade
• BC Cancer Foundation selling branded materials etc.
• IDP
Drug Development Process Flow
In Vitro
In Vitro
Tests
Tests
Dose
Dose
Range
Range
Finding
Finding
FormuFormulation
lation
Go/No Go
Go/No Go
PK/PD
PK/PD
Go/No Go
Go/No Go
Documentation
Documentation
Assay
Devel.
Efficacy
Efficacy
GLP
GLP
Toxicity
Toxicity
Stability
Stability
Testing
Testing
Documentation
Documentation
GMP
GMP
Manuf.
Manuf.
Phase I
Phase I
Clinical
Clinical
Trial
Trial
Clients/Collaborations
• Studies performed one of four ways:
– Full fee for service (25% O/H)
– Collaborative research agreements (15% O/H)
– Co-application on grants (no O/H)
– Free
• Pharmaceutical/Biotechnology companies
• Academia
• BCCA researchers/oncologists
Drug
Discovery
Drug
Formulation
In vitro
Activity
Preclinical
Testing
Analytical/
Stability
cGMP
Regulatory
Clinical
Trials
Marketing
& Sales
Technology Development Office
Our Staff
• Academic institution
–
–
–
–
–
Union
Non-union
Students
Management – permanent contract employees
casual
Source: http://www.msd.com.hk/health_info/drug_education/e_ddp_introduction.html
In Vitro Assays
• Cytotoxicity
– MTT
– Alamar Blue
• Clonogenicity
• Drug penetration
– Multilayered cell
transport
Minchinton et al. Nature Reviews Cancer 6, 583–592
(August 2006) | doi:10.1038/nrc1893
Anti-Cancer Therapy Research
and Development: In Vivo
•
•
•
•
•
Tolerability
Plasma elimination
Pharmacokinetics
Metabolism
Efficacy
– Murine tumour models
– Human xenograft tumour models
– Hypoxia/vascularization
• Small animal GLP Toxicology
Days post inoculation
1
Ventral
Brain
5
Ventral
Lungs
12
Ventral
Rib cage
19
15
Dorsal
Adrenal
Ventral
Ovary
Dorsal
Ventral
Heart
GLP Toxicology
• SOP driven
• Fulfils requirements for IND or CTA for rodent
studies
• Performed in mice or rats
• Single dose range finding or acute studies
• Repeat dose studies
• Acute, chronic or subchronic toxicity
• Includes comprehensive cbc/diff and chem screen
results and full histopathology report
Anti-Cancer Therapy Research and
Development: Formulation/Analytical
•
•
•
•
•
•
Solubility/formulation
Formulation Scale-up
UV/Vis spectrophotometry
HPLC and LC/MS
GC
Full development and
validation services
Anti-Cancer Therapy Research
and Development: Manufacturing
•
•
•
•
•
GMP Compliant Manufacturing
Health Canada licensed pharmaceutical
clean room
GMP and bench batches of formulated
pharmaceutical agents, both conventional
aqueous-based and emulsions
Product inspection & labelling
Stability protocols
Documentation, Documentation,
Documentation!
Prep Room
Batching Room
Storage & Testing Facilities
• Storage of Raw Materials,
supplies and final drug
products in controlled access
rooms of IDP on the 5th
floor, BCCRC
• Refrigerators, freezers and
incubators are maintained on
emergency power and are
continuously monitored
using a validated monitoring
system with remote 24/7
access and control
• Equipment rooms are
monitored for temperature
and humidity
Stakeholders
Stakeholder
Type
Description of Power/Interest
Clients
Key
High power – revenue source. Greater variety of services would
be desirable.
Dr. Karen Gelmon
Key
Functional head of IDP
BCCA Technology
Development Office
(TDO)
British Columbian cancer
Employees
patients: current and future
Investors
Graduate students and post
doctoral fellows in the
Department of Advanced
Therapeutics
Secondary
Primary
Key
Key
Secondary
Relatively high – will have to structure any deal that happens.
Are interested in optimal business model for maximal
benefit to BCCA
Relatively low power. Will support development of novel
Relatively low power. Want to retain jobs
anticancer therapeutics
High: expansion requires financing
Low power; are currently able to access skill set within IDP
Finances
Salaries
Maintenance
Utilities
Shared costs with academic unit
PHSA accounting
Clinical Trial Development &
Support
• In-house developed novel therapeutics
• Client-developed novel therapeutics
• Consultation with Oncologists and
protocol development
• Resource and research ethics approvals
• Patient sample collection and processing
– Pharmacokinetic sampling and specimen
preparation lab area (in collaboration with
Advanced Therapeutics/Investigational
Drug Products), (dedicated centrifuges, 70 & -20 freezers, etc.)
Qualification, Validation &
Calibration
• Written policies in place for qualifying,
validating and calibrating all critical
equipment and procedures involved in the
production and testing of pharmaceutical
products, the IDP and the Clean Room
facility.
• Instrument maintenance & calibration files
maintained on all equipment
Quality Control
• Approves or rejects manufactured drug products
• Oversees adequate laboratory facilities;
• Qualification and maintenance of equipment &
validation of testing methods;
• Documentation control system;
• Oversees stability testing and reporting;
• Responsible for training related to GxP;
• Development and implementation of SOPs,
validation/study/qualification protocols and
reports.
Quality Assurance
• Assesses the conformance of activities in the IDP
with quality management systems in place,
including:
– conducts audits and inspections (both internal and
external); monitors for compliance with SOPs
– reviews all documentation, both GMP and GLP, for
compliance with FDA and HPFBI regulations;
• Manages archives (5 yrs or longer);
• Issues document review/revision forms for SOPs,
distributes SOPs
• Performs annual review of training records.
Quality Management
• Combined QC/QA
– Plus Continual Quality
Improvement
• To ISO 9001
standards
• IT
– 21 CFR Part 11
ISO 9001:2000 Quality Management Systems - Requirements
25
20
15
Number of Canadian Biotechnology
Companies by Year
10
420
5
0
1921 1931 1941 1951 1961 1971 1981 1991 2001 2011 2021 2031 2041
Year
Seniors, as percentage of the total Canadian
Population (1921 – 2041) (Health Canada, 2002)
Number of Canadian Biotech Companies
Seniors in Canadian Population (% of Total)
Projected Increase in Demand for
CROs
400
380
360
340
320
300
280
260
1997
1998
1999
2000
2001
2002
2003
Year
Adapted from http://www.statcan.ca/cgi-bin/downpub/listpub.cgi?catno=88F0006XIE
BC Cancer Agency Translational
Cancer Research Centre
• By 2010, tripled new patient accrual anticipated
justifying the need for a state of the art clinical
trials treatment centre
• Creation of an accessioning, prep, storage,
shipping and packaging within the new
Translational Clinical Trials Centre
• Creation of four additional clean room facilities
encompassing biological, radiopharmaceutical,
cytotoxic and stem cell capabilities
New Manufacturing Space
•
•
•
Pharmaceutical Technology Oct 2006
Firms highly value oncology
expertise for services that involve
cell-based assay for efficacy,
animal models for efficacy testing
as well as for clinical trials.
Firms do not value expertise in
oncology for services such as
toxicology, PK/PD, pathology; nor
do they value it for manufacturing
services.
Growth of biotechnology is twice
as fast as in the pharmaceutical
sector; and by their nature
Biotechnology firms are more
likely to outsource (50% vs. 15%)