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

Berlin, 14.02.2012Dr. Ingrid Lux

05 March 2008 CNN.comApril 28, 2008,

The New York TimesEDITORIAL

The Frightening Heparin Case

Researchers Identify Contaminant in Tainted HeparinApril 23, 2008

Berlin, 14.02.2012Dr. Ingrid Lux

How could that occur?

Authority

Counterfeit

FDA

Pharmaceutical company

Manufacturing company API Supplier

Quality Agreement - components -

Berlin, 1402.2012Dr. 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

Advantages and Limitations of a Quality Agreement

Berlin, 14.02.2012Dr. 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

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, 14.02.2012Dr. Ingrid Lux

ICH Q10- published June 2008 -

Berlin, 14.02.2012Dr. 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

GMP-Guide – revised Chapter 7 Outsourced Activities

Berlin, 14.02.2012Dr. 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

The Supply Chain

Berlin, 14.02.2012Dr. Ingrid Lux

Excipients

BulkManufacturer Packager:

FDF

Warehousing / Transportation

Analytics

Distribution to the market

Active ingredients

Intermediate release Decisions / Contracts

Final Release

Contractor selection process

Berlin, 14.02.2012Dr. 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

Change Control

Evaluation tool

Berlin, 30.11.2011Dr. Ingrid Lux

The Supply Chain

Berlin, 14.02.2012Dr. Ingrid Lux

Excipients

BulkManufacturer 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

Addressing risk in contract manufacturing

Berlin, 14.02.2012Dr. Ingrid Lux

Reactive measuresIncrease 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

Paradox management

Low prices

Berlin, 14.02.2012Dr. Ingrid Lux

High Quality

Highly regulated markets

Fierce pace of changes

Increased knowledge demand

Decreasing development funds

Berlin, 14.02.2012Dr. Ingrid Lux

Cross-departmental risk classification

BusinessMarket actions like distribution stop or recall affects sales and reputation => business vs. quality

ComplianceDynamic pace of changes may lead to regulatory incompliance => Build-up of strong change control tools

Quality & EfficacyLack of tracking may end in efficacy and safety risk => detailed monitoring steps

SAFETYImmediate action required!

RELEVANCE FOR THE PATIENT

Every time

In timePerformance

Costs

Standards

Quality

Mission

Berlin, 14.02.2012Dr. Ingrid Lux

SANDOZ

Platform of contract manufacturers

MEET EXCEED

Competence Knowledge

Productivity Personal development

Integrate

Berlin, 27 September 2011 Dr. Ingrid Lux 29www.taramtamtam.com/.../images/

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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.