mah responsibilities including the management of cmos qp … ·  · 2018-02-08mah responsibilities...

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?

5

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 –

Robert.Byrne@alexion.com

Eoin.Duff@alexion.com