Marketing Authorisation Holder Responsibilities

Background

MA Holding entities are subject to Market Compliance Inspections by any Health Authority, in any EU country where they hold an MA. The HPRA carry out multiple MAH Market compliance inspections each year. These inspections are in addition to GxP inspections of manufacturing sites (GMP/GDP) or PV (GVP inspections). Market Compliance Inspections can encompass all RA/QA/PV aspects of the MAHs business and can involve any ‘customer-facing staff’.

In January 2022 EMA published its “Reflection paper on Good Manufacturing Practice and Marketing Authorisation Holders”. The paper has taken in to consideration those MAHs not involved in manufacturing activities and so-called “virtual MA Holders”.

Acorn Regulatory has worked with a number of MAHs including “virtual MAHs” to help them understand their responsibilities and develop a QMS suitable for their needs and to support them with each of these responsibilities.

Overview

Regulatory Responsibilities

1. Marketing Status/Supply Notifications to Regulatory Authorities
2. Have systems in place for the Maintenance of an up-to-date MA, including regulatory tracking
3. Have procedures in place to carry out Variations to MA
4. Responsible Marketing and Advertising of the Medicinal Product in line with the IPHA code of practice
5. Establishment of a Scientific Service and medical information
6. Facilitate Regulatory Compliance inspection of MAH by Component Authority

Pharmacovigilance Responsibilities

1. Provision of EU-based Qualified Person Responsible for Pharmacovigilance (QPPV)
2. Management of Pharmacovigilance System Master File (PSMF) and Eudravigilance database
3. Global & Local Literature Review
4. Adverse Event Case Processing and Reporting
5. Signal Detection
6. Risk Management Plan
7. Generate & Submit Periodic Safety Update Reports in line with EU Data lock point
8. Carry out Internal Audits of PV system
9. Facilitate PV Inspections by Competent Authority
10. PV Training of all customer-facing staff

Quality Responsibilities

1. Oversight of contract sites and Technical Agreements, including tracking system and reviews
2.  Audits and qualification activities, including GMP status of the API manufacturer and risk-based supplier/service provider qualification
3. MAH Communication with manufacturing sites in relation to the MA content, variations and regulatory commitments
4. Product Quality Reviews (PQR), regulatory input, writing and review
5. Procedure to manage Quality defects, Complaints and Product Recalls
6. Continual improvement activities
7. Falsified Medicines Directive – Confirmation of GMP status of the API, Safety Features (Tamper Evidence) & Repository Update (Serialisation), EMVO/NMVO agreements

Recommendations

Acorn advises all of our clients that are the MA holding legal entity to:

• Review the list of MAH responsibilities and identify who is carrying these out on your behalf
• Ensure there is MAH quality management system (QMS) to manage these responsibilities
• Ensure MAH has appropriate procedures in place to manage any responsibilities carried out in-house and a system for ensuring the appropriate staff are trained on these procedures
• Ensure for any responsibilities outsourced to a 3rd party (including a parent company) that there is a technical agreement in place to cover these responsibilities and supplier is qualified

Next Steps

If you have any questions on your responsibilities as MA Holder, get in with us at info@acornregulatory.com and we’ll be happy to discuss it with you.