outsourcing and supplier qualification

Supplier Qualification

and Regulatory Compliance in

International Biopharm

Logistics

November 19th, Copenhagen, 2015

http://www.nordicqaforum.com/

11/12/2015 CONFIDENTIAL 2

Pharmaceutical Quality Management

Partner Selection and Qualification

Outsourcing and Potential Pitfalls


The area of quality management is undergoing a significant change in

the pharmaceutical industry:

Spotlight is falling on the PQS (Pharmaceutical Quality System)

Drive for efficiency within companies

‘Modern’ science and risk-based thinking and guidance

(e.g. ICH* Q8/9/10) instead of one-dimensional compliance focus

The world has changed…

*International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)



GMP is only a part of the lifecycle of a medicinal product and only a part

of an overall effective Pharmaceutical Quality Management System.

Other quality standards are:

ISO 9000

ISO 9000 series on general Quality Management

ISO 1348

ISO 13485/21CFR820 for Medical Devices

ICH Q10

ICH Q10 defining a Pharmaceutical Quality System

It’s not only about the GxP’s…



Quality assurance is a wide ranging concept which covers all

matters which individually or collectively influence the quality of the

product. It is the sum total of the organized arrangements made

with the object of ensuring that medicinal products are of the quality

required for their intended use. Quality assurance therefore

incorporates GMP plus other factors outside the scope of the

GMP Guide such as

03.24.14 CONFIDENTIAL 5

How the regulators see it


Formalised business practices that define management

responsibilities for organisational structure, processes,

procedures and resources needed to fulfil product/service

requirements, customer satisfaction and continual

improvement.

How the regulators see it

03.24.14 CONFIDENTIAL 6


A Quality Management System has to always to look at the big picture.

Is is the sum of all the management arrangements and the top

management’s total approach to quality.

Design of a state-of-the-art QMS


PLAN what they

need to do

DO what they

need to do

CHECK that it

has been

done correctly

ACT on the information

and results to improve

the way it does things


Evolution of regional GMPs 1970s

Evolution of ISO 9000 approaches 1980s

FDA 21st Century initiative 2002

ICH Quality Vision / Q8, Q9, Q10 2003

FDA Quality Systems guide 2006

ICH Q10 Pharmaceutical Quality System 2005/2008

Where are we currently?



ICH Q10 aims to promote a paradigm shift from discrete GMP

compliance procedures at each stage of the product lifecycle to a

comprehensive quality systems approach over the lifecycle of the

product.

The objective is to:

- Achieve product realizations

- Establish and maintain a state of control

- Facilitate continual improvement

Purpose of ICH Q10



ICH Q10

Will expand existing GMPs with specific PQS elements and

management responsibilities

Encourage science and risk based approaches

Be used together with existing GMPs

Cover all stages of the product lifecycle as defined (beyond GMPs)

Outsourced activities/purchased materials should be within the

scope of the PQS

ICH Q10 and GMP’s –How do they go together?




What are the key elements?

GMP ISO 9000 ICH Q10

GMP’s

Management Responsibility

Continual Improvement

Knowledge Management

Quality Risk Management

Lifecycle Approach

Opportunities

Why GxP | A short history of how GMP evolved Important dates


GDP Enters the Scene


From the Introduction: WHO Technical Report No. 937 Annex 5 (2006) → 40 years on…

meanwhile superseded by No. 957 (2010)

“The quality of pharmaceutical products can be affected by a

lack of adequate control over the numerous activities which

occur during the distribution process.”

Courier/Transport companies are therefore the (weakest?) link

in the supply chain between Manufacturer and point of

dispense/use

From the Introduction: WHO

Technical Report No. 937

Annex 5 (2006) → 40 years

on… meanwhile superseded

by No. 957 (2010)

The Shifting Focus in GDP

“Distribution is an important activity in the integrated

supply-chain management of pharmaceutical products.”

“The nature of risks involved is likely to be similar to that

for risks encountered in the Manufacturing environment”

“Counterfeit pharmaceutical products are a real threat to

public health and safety. Consequently, it is essential to

protect the pharmaceutical supply chain against the

penetration of such products.”

“Every activity in the distribution of pharmaceutical

products should be carried out according to the principles

of GMP, (…), GSP (…) and GDP (…).”


From the Introduction: WHO

Technical Report No. 957

Annex 5 (2010)

European Changes


GDP Guideline (2013/C 343/01) - November 23rd 2013

Greatly expanded

10 Chapters

Legal Basis: Article 84 & 85b subs. 3 of Directive 2001/83/EC

New Directive 2011/62/EU to fight Counterfeit Medication

Original GDP Guideline 94/C 63/03 (1994)

Guidelines on Good Distribution Practice of Medicinal Products for Human Use

General Guideline with less than 4 pages

Legal Basis: Article 10 of Council Directive 92/25/EEC

GDP Guideline (2015/C 95/01) for active substances - March19th 2015

Good Distribution Practice of active substances for medicinal products for

human use

Legal Basis: Article 47of Council Directive 2001/83/EC

The Shifting Focus European changes


1. Quality Management

QMS/Risk Mgt/Mgt Review/Change Control

2. Personnel

Responsibilities/Training/Hygiene

Key Concept “Responsible Person

similar to the QP function in GMP (Ch. 2.5)

3. Premises and Equipment

Handling/e-Systems/Qualification

4. Documentation

Signatures/Archiving/SOPs

5. Operations

Storage/Separation/Destruction

FEFO replaces FIFO

GDP Guideline 2013

Malta

Italy Spain

Portugal

Cyprus

Greece

Bulgaria

Romania Slovenia

Austria Hungary

France

Slovakia

Czech

Republik

Luxemburg Belgium

Netherlands

Germany Poland

Lithuania

Latvia

Estonia

Finland

Sweden

Denmark United

Kingdom

Ireland


6. Complaints, Returns, Suspected Falsified

Medicinal Products and Medicinal

Products Recalls

Training for Increased Awareness

7. Outsourced Activities

New Chapter/Qualification

8. Self-Inspections

New Requirement (3rd Party Audits allowed)

9. Transportation

Risk based approached/“Ship as stored“

10. Specific Provisions for Brokers

New/Broker Activities defined


Malta

Italy Spain

Portugal

Cyprus

Greece

Bulgaria

Romania Slovenia

Austria Hungary

France

Slovakia

Czech

Republik

Luxemburg Belgium

Netherlands

Germany Poland

Lithuania

Latvia

Estonia

Finland

Sweden

Denmark United

Kingdom

Ireland

GDP Guideline 2013



Malta

Italy Spain

Portugal

Cyprus

Greece

Bulgaria

Romania Slovenia

Austria Hungary

France

Slovakia

Czech

Republik

Luxemburg Belgium

Netherlands

Germany Poland

Lithuania

Latvia

Estonia

Finland

Sweden

Denmark United

Kingdom

Ireland

Clarification Documents regarding

Temporary storage and

Holding refrigerated goods

(August 2014)

MHRA:* 36 hours

HPRA:** (formerly IMB) 48 hours

For longer holds and for any holds of

Refrigerated Product a WDA is required

* Medicines & Healthcare products Regulatory Agency

** Health Products Regulatory Authority

GDP Guideline 2013


Chapter 7 EU GMP Guideline revised

(Published 11 September 2012)

Review and Control of all

Outsourced Activities

(Risk based approach)

Responsibility to assess

Legality, Suitability and Competence

of subcontractor

Continuous assessment of

Quality and Performance

(identify and implement improvements)

-> Audits!

Review of Records and Results and Conformity

of Services rendered.

European changes

Malta

Italy Spain

Portugal

Cyprus

Greece

Bulgaria

Romania Slovenia

Austria Hungary

France

Slovakia

Czech

Republik

Luxemburg Belgium

Netherlands

Germany Poland

Lithuania

Latvia

Estonia

Finland

Sweden

Denmark United

Kingdom

Ireland

The Shifting Focus

GMP Updates Already Implemented

31 January 2013


The “Holistic Approach” of a PQS and nearly all regulatory guidelines

agreed upon that the management of outsourced activities and

purchased materials must have processes in place which:

Assess suitability of contractors / suppliers before use

Ensure use of approved suppliers and a defined supply chain

Define responsibilities and communication processes for quality

related activities

Review performance and make improvements



1. Define selection parameters

2. Establish weighting criteria for selection parameters

3. Gather information from LSP’s via questionnaire

4. Rate LSP on selection parameters

5. Calculate overall weighted score and overall rank

6. Generate short-list of candidates

7. Perform evaluation audit(s)

8. Appoint LSP

Stepwise approach




• Foreign Corrupt Practices Act

GDP Compliance exception for logistics companies Irish Exporters Association / Life Sciences

Definition of selection parameters (example)

Selection Parameter Description Scoring criteria

Compliance

Certification (SQAS, ISO 9001/14001, CT-PAT, GDP(?),

FCPA*) Certificate

Pharma reference customers # of references

Competency Cold Chain, DGR/ADR, Narcotics # of accounts

Customs Own vs. contracted agencies

Dedicated pharma organization Type of setup

QMS available & implemented in organization Dedicated, shared, none

Commercial Offer Completeness of offer # of covered routes

Quality of data received 1 to 10

Range of possible services # of service modes

Management by KPIs Existing, planned, no

Implementation &

Development Implementation readyness Timeframe

IT Compatibility Full, partly, no

Track & Trace Capabilities / Milestone reporting Own tool, outsourced, none

Innovation / Drive to change 1 to 10

Company Size Turnover

Global Network # of sites

Financial situation Profitable, break-even, non-profitable



Gather information via questionnaire

Question Supplier 1 Supplier 2

1. Compliance 1. Compliance 1. Compliance

1.1. Have you already been certified (SQAS, ISO 9001/14001, CT-PAT, CEP, GxP etc.) and audited by an offical body in Germany? By whom? Certificates are still valid?

1.2. Which pharmaceutical references do you have for distribution out of Germany? May [company] get in contact with them in order to get convinced from your pharmaceutical experience?

1.3. What is the longest duration of an pharmaceutical customer relationship/contract?

1.4. What is your competence in Cold Chain, DGR/ADR, Narcotics and Legalization? Please state the number of accounts per commodity as mentioned before.

1.5.



Establish weighting factors

Score 1-10 (10 highest)

Scoring

Overall

Weighting Selection Criteria 1 2.5 5 7.5 10

Compliance No Partial Yes 35%

Commercial Offer No Partial Yes 30%

Implementation / Future

Development No Partial Yes 20%

Company No Partial Yes 15%

Total 100%



Weighted score and overall rank

0

2

4

6

8

10

12

14

16

18

20

22

Compliance

Commercial Offer

Implementation/FutureDevelopment

Company

LSP Qualification by Selection Criteria (weighted rating)

Supplier 1

Supplier 2

Supplier 3

Supplier 4

Supplier 5

Supplier 6

Supplier 7

Supplier 8

Partner Selection and Qualification Perform evaluation audit


Make sure that any departure & intermediate hubs are integrated as well!

Audit shall be carried out at both headquarters and branch office

Involve contracted GHA’s if applicable

Main observations are:

- Lack of training

- Missing/incomplete documentation

>No/not adequate change control

>No process for deviation of handling

- Non-qualified premises (for GHA’s)

Establish GDP-compliance plan


Quality Agreement

Documentation of processes

and workflows

Change control

Deviation handling

Training

Areas for pre-go live qualification



Contact details

Hours of operation

Public and company

holidays

Products and special

requirements

Packaging components

Documentation

Labeling

Pickup

Re-icing

Documentation of processes and workflows


Topics that should be covered include:

Special requirements at

origin and destination

Pre-alerts

Irregularities

Tracking & tracing

Partner Selection and Qualification Training


Develop training modules for the specific needs

Make sure that both parties talk the same language

Include all staff levels for the trainings

Keep the ball rolling – every change could result in lack

of knowledge

Ongoing performance management: deviations



Partner Selection and Qualification Monthly performance monitoring (examples)


0

2

4

6

8

10

12

14

16

18

Supplier 1 Supplier 2 Supplier 3 Supplier 4 Supplier 5 Supplier 6 Supplier 7 Supplier 8 other

Crosslabelling Customs Damage Handlingtime Loss (partial) Loss (temporarily)Loss (total) Notification other Splitting Wrong destination

Measurement per reason code/carrier

0

20

40

60

80

100

120

=< 5working

days

=< 10working

days

=< 15working

days

=< 20working

days

> 20working

days

open

Co

mp

lain

ts

Measurement of response time

Outsourcing Logistics Services - Pitfalls

Quality should not only be done by the “Q-Team”

The selection and qualification of LSP has to involve

several departments i.e. logistics, clinical, production,

project management, etc.

Be aware if outsourced activities are sourced out

Most audits of potential vendors are performed at

headquarters or nearest branches but clinical trials are

conducted across the world and in remote countries or

locations. It is necessary to evaluate the suitability also

of international branches, agents or drivers.



Don’t get too obsessed with details

Sometimes companies are trying to integrate all details

into a Quality Agreement or are pushing for a

shipment/transport qualification/validation. If

requirements are too tightly defined or get too strict,

there is a risk of being unable to react if setups change

during trials or irregularities occur during transportation.

Don’t be too general either

Although regulatory requirements are seen as largely

compulsory, it is not enough to qualify a vendor once

and for all potential tasks. Each project and trial is

different or has changed requirements and therefore

one should consider to re-qualify vendors for new

projects.



A questionnaire is no real involvement

It is crucial to involve the LSP in project details during

the selection and qualification process.

Clinical trials get more and more complex these days

(i.e. patient recruitment, sample drawing, sensitivity of

the shipped commodities, etc.) and require a good

understanding of the details at an early stage (example

regenerative medicine).

Misunderstandings or unclear requirements often result

in costly delays of the project.

Are all necessary parties

(Sponsor/CRO/Lab/CMO/Packer/etc.) directly involved

in the selection and qualification process?



Share your thoughts and performance reviews

Often performance reviews are not frequently shared

with the LSP – except deviations which require a

feedback, i.e. CAPAs.

Continuous improvement is only possible by open and

frequent exchange among the partners.

Set up a frequent exchange process for reports and

quarterly or half year reviews



Choosing the right Supplier Moving towards GxP compliance

1. Quality Systems:

Processes and SOPs

2. People:

Education/Training/

Experience

3. Technology:

Packaging and Monitoring

Michael Fleischer Director, Quality – Transport GMP Compliance and QA Manager Certified Lead Auditor

Thank you for your attention

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