Title: Organization of Clinical Operations at a CRO
1- Organization of Clinical Operations at a CRO
- Anil Kane, Ph.D
- Patheon Inc.
- akane_at_patheon.com
2Outsourcing Clinical Manufacturing
- Outsourcing Pharmaceutical Industrys strategic
- tool
- Outsourcing increased dramatically since 1990s
- Today pharma companies outsource 20-40
- of the development budget
- Approx. 60 of R D spent on clinical trials
- hence clinical supply management critical to
- development budget / time.
2
3Outsourcing - Clinical Manufacturing
Pharmaceutical outsourcing in the US is now
over US 30 billion - Arthur D.Little
3
4Outsourcing Clinical Manufacturing
Sponsor / contractor relationship
- Past
- Master / slave relationship
- CROs at the whim of sponsors
- Today a paradigm shift
- Sponsor / CRO strategic partnership
- stronger and long term relationship
- risk / profit sharing opportunities
4
5Drivers to Outsourcing Clinical Manufacturing
- to accelerate drug development
- enhance competitiveness
-
- access world class technology / global
manufacturing - infrastructure
- utilize expertise / experience of a CRO
- focus internally on core competencies
5
6Drivers to Outsourcing Clinical Manufacturing
- Lower capital investment, higher ROI (capital
risk) - cover gaps in capacity
- access to focused flexible manufacturing
infrastructure - ensure a more tidy regulatory process
6
7Drivers to Outsourcing Clinical Manufacturing
- Contractors have a vast experience working with
many more - molecules and complexities than many individual
- pharmaceutical houses.
- Contractors offer creative solutions to their
sponsors - Contractors have approved vendors resulting in
better quality - assurance of RMs / PMs
- Contractors have regulatory experiences
- sites are FDA approved
7
8Drivers to Outsourcing Clinical Manufacturing
- Logistics of procurement advantage with a
contractor - Bulk procurement of RMs / PMs reduce overall
costs for - small clinical supplies
8
9Drivers to Outsourcing Clinical Manufacturing
- 55 Companies outsource to improve company focus
- 54 Companies rely on outsourcing to reduce or
control - operating costs
- 38 to free internal resources for other purposes
- 36 to gain access to world class capabilities
- 18 to reduce time to market
- 12 for risk sharing
- Survey The Outsourcing Institute
- a report Interphex 2004
9
10Outsourcing Clinical Manufacturing
- Disadvantages
- reduce organizational innovation
- shift knowledge to suppliers organization
- reduce control over activities
- need a close monitor
- regulatory risk
- Leaking Intellectual property pr being boxed
in by third party - providers
10
11Outsourcing Clinical Manufacturing
Sponsors
- Big Pharma
- Medium size pharmaceutical houses
- Biotech companies
- Virtual to small companies
11
12Outsourcing Clinical Manufacturing
- Evaluating a potential outsourcing partner a
checklist - Capability
- Experience
- Expertise
- Speed
- Track Record
- Capacity
- Right resources (equipment, personnel)
- Responsiveness to changing requirement
12
13Outsourcing Clinical Manufacturing
- Evaluating a potential outsourcing partner a
checklist - Quality
- Quality control procedures and processes in
place. - Continuous monitoring
- Compliance
- understanding of applicable regulations
- established QA plan
- archiving system
13
14Outsourcing Clinical Manufacturing
- Evaluating a potential outsourcing partner a
checklist - Financial considerations
- financial stability
- long term viability
- cost of services
- Culture
- ability to build a lasting, mutually profitable
relationship - with sponsor
14
15Outsourcing Services at CRO
- API characterization
- API Stability
- Preformulation
- Analytical Methods development
- Dosage Form Development
- Dosage form Stability
- Packaging Development
- Clinical Manufacturing
- Packaging
- Shipping
- Storage Distribution
15
16Clinical Supply
Active or placebo preparation used in clinical
programs for the determination of safety and /
or efficacy of a pharmaceutical formulation.
- Material for Toxicology studies / animal PK
study - Phase I II supply
- Phase III trials
- Phase IV supplies (generally from commercial
supplies)
16
17Clinical Manufacturing Operations
Formulation Dev.
Project Management
Analytical Dev.
Business Dev.
Sales, Marketing
Manufacturing Packaging
Materials Mgt.
Quality Control
Services-IT Eng.
Quality Assurance
Regulatory CMC Group
17
18Clinical Manufacturing Operations
QC/ Release Testing
Project Planning
Clinical Manufacturing/ Packaging - GMP facility
Materials
Clinical Stability
Info from FD/AD
Shipment
Documentation
18
19Critical Steps in Outsourcing Clinical
Manufacturing
- Confidentiality Disclosure Agreement (CDA)
- prerequisite for any project discussion
- reviewed and signed by both parties legal
counsel - evaluate project feasibility
19
20Critical Steps in Outsourcing Clinical
Manufacturing
- Intellectual Property Rights
- ownership of IP
- Importance of contracts, assignments and
licenses - addressed through diligence and Good Contractual
Practices
20
21Critical Steps in Outsourcing Clinical
Manufacturing
- Quality Audits
- Self Audit by contractors
- Sponsor audits
- cGMPs
- IQ/OQ/PQs of equipment, HVACs, Water etc.
- Training
- Corrective Action / Preventive action (CAPA)
Plan - Regulatory Inspection track records
- References
21
22Critical Steps in Outsourcing Clinical
Manufacturing
- Project Questionnaire
- completed by sponsor
- clear definition of project scope (activities,
responsibilities - timelines)
- useful tool to communicate project requirement /
expectations - to contractor
- Alternatively this is captured in Request for
Proposal (RFP)
22
23Critical Steps in Outsourcing Clinical
Manufacturing
- Project Questionnaire should answer the following
questions - drug classification (toxicity, therapeutic class
etc) - availability of MSDS
- handling procedures / precautions
- special storage conditions / requirements
- phase of the clinical program
- cleaning verification requirement
- requirement of analytical method/s development,
formulation - development
23
24Clinical Manufacturing Plan / Proposal / Quote
- well laid out steps in the project execution
- detailed timeline for deliverables
- assumptions
- back up plan
- cost estimate for the project
-
24
25Clinical Manufacturing Operations
- Cleaning Verification Program - Master
Validation Plan - Product specific -
Contractor responsibility for compliance
25
26Clinical Manufacturing Operations
Effective Project Management key to a successful
partnership key to a successful execution /
timely completion key to building long term
relationship / future collaboration
26
27Clinical Manufacturing Operations
- Analytical Development Laboratories
- strong team of experienced analytical chemists
- skills in Preformulation to Analytical support
for routine testing - complete, flexible infrastructure to meet a
variety of client / project - requirement
27
28Clinical Manufacturing Operations
- Formulation Development / Process Development
- most projects need some development / tech
transfer work - prior to clinical manufacturing hence the
requirement for - formulation development infrastructure / pilot
plant - trained, experienced formulators / process
development staff
28
29Clinical Manufacturing Operations
- Materials Management / Sourcing
- procurement of raw materials
- procurement of packaging materials
- experienced staff a key to sourcing materials
in a timely - manner
29
30Clinical Manufacturing Operations
- Manufacturing set up
- systems planning / scheduling manufacturing
jobs - feasibility of manufacturing a variety of dosage
forms - equipment / process trains for different scale
of operations - skilled, trained experienced operators for
manufacturing / - packaging
-
30
31Clinical Manufacturing Operations
- Packaging
- flexibility in packaging different dosage forms
- primary packaging
- secondary packaging
- clinical kit - packaging
31
32Clinical Manufacturing Operations
- Quality Assurance / Compliance
- SOPs
- Training Curriculum
- cGMP compliance
- Approval of documents Master Batch Records,
Deviation - reports, change controls, Reports etc.
32
33Clinical Manufacturing Operations
- Quality Control / Analytical Release Testing
- In-process Testing
- Bulk product release
- Packaged product release
- Generation of CofAs
33
34Clinical Manufacturing Operations
- Shipment of Clinical supplies
- experienced staff
- export procedures where applicable
- special requirements for shipment (refrigeration
etc.)
34
35Outsourcing Clinical Manufacturing
Its all about building TRUST and long term
strategic relationship
Contractor
Sponsor C
Sponsor A
Sponsor B
35
36Outsourcing Clinical Manufacturing
- Myths about CROs
- Outsourcing to a CRO is more expensive
- Large CROs do not care about small companies.
- Big Pharma gets a priority
- Large CROs do not communicate effectively
- CROs are training grounds hence high turnover.
- CRO does not have the same passion for my
development / - clinical program
36
37Outsourcing Clinical Manufacturing
- Myths about Sponsors
- Large companies do not communicate effectively
- Small companies use the bidding process as a way
of - getting free consulting.
- Small companies always ask for more than they
are willing - to pay for.
37
38Outsourcing Clinical Manufacturing
Key Partnership Elements
- Dos
- Understand each others wants and needs
- Establish project milestones and/or service
model - Develop a sense of common purpose
- Donts
- Underestimate the need for information exchange
- Assume that information flows perfectly
- Keep apart functions that need to be
co-ordinated - Keep trouble a secret
38
39Sponsor CRO Relationship
- Key Elements for Success
- Mutual Trust and Respect
-
- Clarity in Responsibilities
-
- Clarity in contractual and payment terms
-
- Channel of Communication
-
- Minimal changes to team
-
39
40Sponsor CRO Relationship
Key Elements for Success
- Tolerance in diversity of opinion
- Efficient Project Management Tools
- Open / honest discussion for problem
- resolution
- Measure Progress
40
41The Right Capacity
The Right Services
The Right People
Outsourcing Clinical Manufacturing
41
42Outsourcing Clinical Manufacturing
- Good Clinical Trial Manufacturing Contractor has
facilities and systems - equivalent to those in Big Pharma
- Reasons for outsourcing time, capacity,
infrastructure etc. - Key to Success - Information Flow
- - Effective Project Management
- Repeat Business TRUST / RELATIONSHIP
42