MAH Responsibilities and the Role of the QP Ann McGee Managing Director Pharmalex Ireland QP Forum 12th April 2018 © PharmaLex

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MAH Responsibilities and the Role of the QP Who is the Marketing Authorisation Holder (MAH)? The Company or other legal entity in whose name the Marketing Authorisation has been granted Typically a legal entity with no organisational structure Often the MAH is the Regulatory function of an affiliate MAH responsibilities cannot be delegated. Activities can be delegated but still require oversight by the MAH Role of QP?? Who takes responsibility for what? How many MAHs have a structured QMS, for example a structured change management system? What does all this mean? © PharmaLex

MAH Responsibilities and the Role of the QP What is the level of QP in organisation? Who do they report to? Are they involved in decision making? Have they got the required visibility? Are they kept informed of MA variations? Do they have input into significant change controls; new product introduction? © PharmaLex

MAH Responsibilities and the Role of the QP 1. Control of Clinical Trials / Studies (pre and post marketing 10. Control of responsible Marketing and Promotion 2. Oversight of manufacturing from API to QP release to market 9. Provision of Medical information Legal Obligations of Marketing Authorisation Holder (EU) Related activities may be delegated but responsibility is retained by MAH 3. QP Arrangements 8. Pharmacovigilance & QPPV 4. Control of Labelling and Packaging 5. Supply and Distribution 7. Complaints, Quality Defects and Recall 6. RP Arrangements © PharmaLex

MAH Responsibilities and the Role of the QP Responsible for ethical clinical trial design and execution 1. Control of Clinical Trials / Studies (pre and post marketing MAH MAH Clinical trials/studies must be managed in compliance with GCP Considerations for the QP What clinical trials is the organisation conducting? QP review of batch record Release of batch according to Annex 13 © PharmaLex

MAH Responsibilities and the Role of the QP Oversight of the supply chain to ensure medicinal products are manufactured and distributed in accordance with GMP and GDP and to ensure that falsified medicines are prevented from entering the supply chain 2. Oversight of manufacturing from API to QP release to market MAH EudraLex Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use Annex 16: Certification by a Qualified Person and Batch Release © PharmaLex

MAH Responsibilities and the Role of the QP © PharmaLex

MAH Responsibilities and the Role of the QP QP – review of the documented supply chain How can the QP gain assurance? Who are the stakeholders in supply chain? What about physical transport considerations? What about storage considerations? What about product ownership? What about financial transactions? What about compliance status? Knowledge of control of supply chain Vendor qualification and management Quality agreements with stakeholders External audits Change management © PharmaLex

MAH Responsibilities and the Role of the QP Provision of a QP QP as the eyes and ears of the MAH & structures to enable this to operate 3. QP Arrangements MAH Considerations Multiple QPs in the chain QP at a CMO QP to QP agreements How to ensure that Contract QPs are kept current? Is the QP satisfied that they have connections with the right people – RP, QPPV? © PharmaLex

MAH Responsibilities and the Role of the QP Must be current and correct Liaison between MAH and manufacturing/batch release sites Regular review of finished packs from batch release sites 4. Control of Labelling and Packaging MAH Incorrect labelling is the source of many product recalls How is the QP kept up-to-date on current labelling? Is QP involved in change management process? Does the QP have a relationship with Regulatory Affairs? © PharmaLex

MAH Responsibilities and the Role of the QP GDP requirements Management and control of procuring, supply, distribution, storage, transportation RP roles & responsibilities 5. Supply & Distribution 6. RP Arrangements MAH QP RP © PharmaLex

MAH Responsibilities and the Role of the QP QPPV appointed by MAH Involvement of PhV function? Reporting requirements to authorities 7. Complaints, Quality Defects & Recall 8. Pharmacovigilance & QPPV MAH Relationships QP QP QP RP QPPV QP How are these relationships built and maintained? What is the level of trust? © PharmaLex

MAH Responsibilities and the Role of the QP Contracted activities MAH must ensure an appropriate standard of quality and compliance exists at third party organisations Activities may include: Manufacturing & distribution Logistics Testing and QP release of manufactured product Pharmacovigilance services Regulatory affairs services Management of safety information Supply chain services Contract clinical trial/GCP services Representatives in local markets receiving and forwarding product quality complaints and ADR reports Complaint coordination and investigation at contract manufacturing/distribution sites Recall management at contract manufacturing/distribution sites WHERE DOES THE QP COME INTO THIS?? © PharmaLex

Ms. Ann McGee +353 1 846 4742 Ann.mcgee@pharmalex.com Suite 2 Stafford House Strand Road Portmarnock Co Dubllin D13 H525 © PharmaLex

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9. Provision of Medical Information Medical Information function Establish a scientific service to compile and collate all information relating to product 9. Provision of Medical Information MAH © PharmaLex

10. Control of responsible Marketing & Promotion Back-up slide Activities to be conducted in compliance with IPHA Code of Practice and SI541 (Control of Advertising) Training in these codes/regulations required for relevant personnel MAH 10. Control of responsible Marketing & Promotion Promotional materials Procedures to manage development, approval, distribution, update Ensure only current promotional materials and SmPCs are provided to HCPs MAH MAH Management and control of free medical samples Training for Sales Reps regarding product information, complaint and adverse reactions report handling © PharmaLex