outsourcing and supplier qualification
TRANSCRIPT
Supplier Qualification
and Regulatory Compliance in
International Biopharm
Logistics
November 19th, Copenhagen, 2015
11/12/2015 CONFIDENTIAL 2
Pharmaceutical Quality Management
Partner Selection and Qualification
Outsourcing and Potential Pitfalls
Pharmaceutical Quality Management
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)
11/12/2015 CONFIDENTIAL 3
Pharmaceutical Quality Management
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…
11/12/2015 CONFIDENTIAL 4
Pharmaceutical Quality Management
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
Pharmaceutical Quality Management
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
Pharmaceutical Quality Management
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
11/12/2015 CONFIDENTIAL 7
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
Pharmaceutical Quality Management
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?
11/12/2015 CONFIDENTIAL 8
Pharmaceutical Quality Management
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
11/12/2015 CONFIDENTIAL 9
Pharmaceutical Quality Management
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?
11/12/2015 CONFIDENTIAL 10
Pharmaceutical Quality Management
11/12/2015 CONFIDENTIAL 11
What are the key elements?
GMP ISO 9000 ICH Q10
GMP’s
Management Responsibility
Continual Improvement
Knowledge Management
Quality Risk Management
Lifecycle Approach
Opportunities
GDP Enters the Scene
11/12/2015 CONFIDENTIAL 13
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 (…).”
11/12/2015 CONFIDENTIAL 14
From the Introduction: WHO
Technical Report No. 957
Annex 5 (2010)
European Changes
11/12/2015 CONFIDENTIAL 15
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
11/12/2015 CONFIDENTIAL 16
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
11/12/2015 CONFIDENTIAL 17
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
The Shifting Focus 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
GDP Guideline 2013
The Shifting Focus European changes
11/12/2015 CONFIDENTIAL 18
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
11/12/2015 CONFIDENTIAL 19
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
11/12/2015 CONFIDENTIAL 20
Pharmaceutical Quality Management
Partner Selection and Qualification
Outsourcing and Potential Pitfalls
Partner Selection and Qualification
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
11/12/2015 CONFIDENTIAL 21
Partner Selection and Qualification
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
11/12/2015 CONFIDENTIAL 22
Partner Selection and Qualification
11/12/2015 CONFIDENTIAL 23
• 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
Partner Selection and Qualification
11/12/2015 CONFIDENTIAL 24
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.
Partner Selection and Qualification
11/12/2015 CONFIDENTIAL 25
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%
Partner Selection and Qualification
11/12/2015 CONFIDENTIAL 26
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
11/12/2015 CONFIDENTIAL 27
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
Partner Selection and Qualification
Quality Agreement
Documentation of processes
and workflows
Change control
Deviation handling
Training
Areas for pre-go live qualification
11/12/2015 CONFIDENTIAL 28
Partner Selection and 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
11/12/2015 CONFIDENTIAL 29
Topics that should be covered include:
Special requirements at
origin and destination
Pre-alerts
Irregularities
Tracking & tracing
Partner Selection and Qualification Training
11/12/2015 CONFIDENTIAL 30
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
11/12/2015 CONFIDENTIAL 31
Partner Selection and Qualification
Partner Selection and Qualification Monthly performance monitoring (examples)
11/12/2015 CONFIDENTIAL 32
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
11/12/2015 CONFIDENTIAL 33
Pharmaceutical Quality Management
Partner Selection and Qualification
Outsourcing and Potential Pitfalls
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.
11/12/2015 CONFIDENTIAL 34
Outsourcing Logistics Services - Pitfalls
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.
11/12/2015 CONFIDENTIAL 35
Outsourcing Logistics Services - Pitfalls
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?
11/12/2015 CONFIDENTIAL 36
Outsourcing Logistics Services - Pitfalls
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
11/12/2015 CONFIDENTIAL 37
11/12/2015 CONFIDENTIAL 38
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