1. Risk induced improvement of
relationship with contractors
Dr. Ingrid Lux, Head Quality Control, Qualified Person
Berlin, 14.02.2012

2. Berlin, 14.02.2012
Dr. Ingrid Lux
05 March 2008 CNN.com
April 28, 2008,
The New York
TimesEDITORIAL
The Frightening
Heparin Case
Researchers Identify Contaminant in Tainted Heparin
April 23, 2008

3. Berlin, 14.02.2012
Dr. Ingrid Lux
How could that occur?
Authority
Counterfeit
FDA
Pharmaceutical
company
Manufacturing
company
API Supplier

4. Quality Agreement
- components -
Berlin, 1402.2012
Dr. Ingrid Lux
Denomination of involved
parties
Scope Definition
Responsibilities listed in a table with clear delimitation
between parties
List of contact persons
Attachments including
technical specifications
Signatures

5. Advantages and Limitations of a Quality Agreement
Berlin, 14.02.2012
Dr. Ingrid Lux
Advantages
Clear denomination of
responsibilities
Clear delimitation of responsibilities
Sound focus on GMP and
standardized norms
Limitations
No knowledge infusion
No protection against accidental failure
or deliberate fraud
No direct impact on operational
transformation

6. FDA findings at concerned API supplier during
inspection in April 2008
- quotations -
• “Your firm lacked an adequate evaluation of the effectiveness
of critical processing steps designed to remove impurities “
• “You state that the firm received and used heparin crude
materials from a workshop that had been designated by your
firm in a pre-audit as “unacceptable”.
• “You have failed to conduct adequate verification of USP
compendial test methods as applied to the production of your
firms API.”
Berlin, 14.02.2012
Dr. Ingrid Lux

7. ICH Q10
- published June 2008 -
Berlin, 14.02.2012
Dr. Ingrid Lux
Pharmaceutical quality system
- Knowledge and quality system
transfer
Management responsibility
- Including resource planning
Continual improvement
- of process performance, product
quality, and pharmaceutical quality
system
International
Conference of
Harmonization

8. GMP-Guide – revised Chapter 7
Outsourced Activities
Berlin, 14.02.2012
Dr. Ingrid Lux
Focus on communication processes
Clear definition of responsibilities
reaching out to market impact
Quality system of CG sustained by
management
Comprehensive assessment
Continuous and documented control
of quality
Audit allowance of CA and its
subcontractors

9. The Supply Chain
Berlin, 14.02.2012
Dr. Ingrid Lux
Excipients
Bulk
Manufacturer Packager:
FDF
Warehousing /
Transportation
Analytics
Distribution to the
market
Active ingredients
Intermediate release
Decisions / Contracts
Final
Release

10. Contractor selection process
Berlin, 14.02.2012
Dr. Ingrid Lux
Fixed procedure: GOP, SOP, to
integrate cross-divisional decision
making
Definition of mandatory steps
Managerial responsibilities:
Time critical operations =>
resource planning !
QA-
AUDIT
SCM
SCM
ChangeControl

11. Evaluation tool
Berlin, 30.11.2011
Dr. Ingrid Lux

12. The Supply Chain
Berlin, 14.02.2012
Dr. Ingrid Lux
Excipients
Bulk
Manufacturer Packager:
FDF
Warehousing /
Transportation
Analytics
Distribution to the
market
Active ingredients
Flow of material
Flow of
samples
Intermediate release
Decisions / Contracts
Final release
Flow of decisions

13. Addressing risk in contract manufacturing
Berlin, 14.02.2012
Dr. Ingrid Lux
Reactive measures
Increase monitoring efforts (re-test,
follow-ups etc.)
Remove Supplier from authorized list
of suppliers
Stop supply / destroy stocks
Recall
Proactive measures
Follow internal process of supplier
identification
Follow-up plan with detailed measures
of contract partner
Assess investment to enable support
Foster strategic decision on
management level

14. Paradox management
Low prices
Berlin, 14.02.2012
Dr. Ingrid Lux
High Quality
Highly regulated
markets
Fierce pace of
changes
Increased
knowledge
demand
Decreasing
development
funds

15. Berlin, 14.02.2012
Dr. Ingrid Lux
Cross-departmental risk classification
Business
Market actions like
distribution stop or recall
affects sales and reputation
=> business vs. quality
Compliance
Dynamic pace of changes
may lead to regulatory
incompliance => Build-up of
strong change control tools
Quality & Efficacy
Lack of tracking may end in
efficacy and safety risk =>
detailed monitoring steps
SAFETY
Immediate action
required!
RELEVANCE FOR THE PATIENT

16. Every
time
In time
Performance
Costs
Standards
Quality
Mission
Berlin, 14.02.2012
Dr. Ingrid Lux
SANDOZ
Platform of contract
manufacturers
MEET EXCEED
Competence Knowledge
Productivity Personal
development
Integrate

17. Berlin, 27 September
2011 Dr. Ingrid Lux
29www.taramtamtam.com/.../images/Surfing_
3.jpg

18. Selection Strategy
Mission: building and integrating a platform of contract
manufacturers in partnerships that meet or exceed the defined
quality, costs and performance standards on time, every time,
achieved by one global process, building competence and
knowledge to ensure maximum productivity and personal
development.
Interdepartmental communication: setting quality into the frame
Quality is not only an intrinsic value, an expected property, but
part of the business This is to be reflected in all supplying
decisions.