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MAH Responsibilities including the
Management of CMOs
QP Forum 2017 - Workshop
Robert Byrne and Eoin Duff
Quality Assurance
Alexion Pharmaceuticals
25th April 2017
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Alexion Pharmaceuticals in Ireland
Alexion Athlone Manufacturing Facility – • Vial fill-finish facility • Biologics manufacturing facility (under
construction)
Alexion’s Global Supply Chain Headquarters, Dublin - • Laboratories • Packaging facility • Biologics manufacturing facility (under
construction)
A global biopharmaceutical company focused on developing and delivering life-transforming therapies for patients with devastating and rare diseases.
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Workshop content
• Brief overview focussing on –
○ MAH Responsibilities
○ Qualified Person and the MAH
○ Global Manufacturing
○ Compliance Challenge Examples
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Workshop content
• Interactive discussions
○ Management of CMOs
○ Marketing authorisation dossiers
○ Annex 16 - Non-EU marketing authorisations
○ Handling of unexpected deviations
○ Medicines shortages
○ Other topics?
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MAH Responsibilities – Core Principle
‘The ultimate responsibility for the performance of a medicinal product over
its lifetime, its safety, quality and efficacy, lies with the MAH’
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MAH Responsibilities with Respect to GMP
EU Directives
• Maintain MA in line with scientific advances
• Ensure continued and appropriate supply to meet patient need (Topic 4)
EU GMPs
• PQR review
• Outsourcing
• Quality defects, risk-reducing actions, disruption to supply
• Irradiation cycle design approval and location of records
• Sites of QP certification
• Reference and retention samples
Reference: Concept paper on Good Manufacturing Practice and Marketing Authorisation Holders (EMA/582064/2016)
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Qualified Person and the MAH
Registration Dossier
European Regulator or
Not?
Unexpected Deviations
Management of CMOs
Medicines Shortages
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Global Manufacturing of Medicinal Products
DS
DP FP
ACME Pharmaceuticals
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Contract Manufacturing - Regulator Focus?
• Survey - Has management/oversight/disposition of CMO manufactured
batches been requested during audit of MAH site(s) within the last 3
years?
14/24
10/24
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Compliance Challenges
Workshop Focus Topics
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Topic 1. Management of CMOs
• Focus area – What approach works best?
○ Quality Agreement in association with customer
audits
○ 100% oversight – executed batch record review,
change control and deviation review and
approval
○ Risk based approach – Major/Critical deviations
and product/regulatory impacting change
controls etc.
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Survey Results
• Does your company's QA group perform any level of executed batch record review, batch
specific Deviation or batch specific Change Control review for batches (API/Drug
Substance/Drug Product/Finished Product) manufactured by CMO prior to release?
23/24
01/24
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Survey Results
• What oversight is provided by your company for CMO manufactured batches?
Quality Agreement and Customer Audit Only
Other
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Survey Results
• Is certification of any of the following CMO manufactured batches provided by
your company's Qualified Person (QP)?
0%
10%
20%
30%
40%
50%
60%
70%
Drug Substance/API Drug Product Finished Product (PackagedProduct)
No Certification Provided
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Survey Results
• Does your company use a risk based approach to determine the level of
oversight provided for CMO manufactured batches?
60.9%
26.1%
13.0%
Yes
No
All releases are performed byCMO with no batch releaseactivity/review performed bythe MAH
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Survey Results
• In your opinion should the MAH perform batch review/release/certification of
batches manufactured by CMO if the responsibility has been given to the CMO
and is documented in the relevant Quality Agreements?
11/24
13/24
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Topic 2. Marketing Authorisation Dossiers
• Focus – Dealing with MA dossiers
○ Do you have full visibility of the current
version?
○ Is it complete?
○ Is it harmonised across jurisdictions?
• Aspect 1 – Dealing with
manufacturing sites
• Aspect 2 – Dealing with regulatory
authorities
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Topic 3. Annex 16 - Non-EU marketing authorisations
• Focus area - How does Annex 16 apply to non-EU marketing
authorisations outside of EU?
References: • EU GMPs Annex 16 Certification by a Qualified Person and Batch Release • S.I. No. 539 of 2007 Medicinal Products (Control of Manufacture) Regulations 2007
The functions of the qualified person shall be — ……. to ensure that every batch of a medicinal product to which the authorisation relates has been manufactured and checked in compliance with…. (iii) the provisions of the marketing authorisation, certificate of registration, certificate of traditional-use registration or other standard which relates to the said product
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Topic 4. Handling of Unexpected Deviations - ‘QP discretion’
• Aspect 1 – QP is employed by the marketing authorisation holder
• Aspect 2 – QP is employed by a manufacturing/packing/batch release
site that is not the marketing authorisation holder
○ Challenge – Complete visibility of the marketing authorisation is not available to
the QP
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Survey Results
Is final batch certification by Qualified Person (QP) performed by your company or by a subcontracted party?
0% 10% 20% 30% 40% 50% 60% 70% 80%
By my company
Subcontracted to another company
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Topic 5 – Medicines Shortages
• Focus – MAH/Manufacturing site interaction
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Other Topics?
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Thanks to all for your participation
Please complete Eoin’s survey! https://www.surveymonkey.com/r/CJ5TRBZ
Contact details –
