EU guidance states that the ultimate responsibility for the performance of a medicinal product over its lifetime in relation to its safety, quality and efficacy, lies with the Marketing Authorisation Holder (MAH). The MAH must have appropriate controls in place and operate a Quality Management System to support the activities related to these controls. So, what are the obligations of the MAH? This article provides a summary of the specific responsibilities of the MAH.
Ethical Clinical Design:
The MAH must ensure that clinical trials for the medicinal product are designed and developed ethically, in accordance with relevant EU regulations.
Oversight of Manufacturing from API to release to market:
The MAH must have full supply chain oversight and controls in place to ensure continued availability of safe and effective medicinal products for the patient. Controls must be in place to ensure that medicinal products are manufactured and distributed in accordance with GMP and GDP guidance and that falsified medicines are prevented from entering the supply chain.
Identification of the QP:
A Qualified Person (QP), identified by the MAH has responsibility for checking that each individual batch has been manufactured in line with the terms of the marketing authorisation (MA) and with Good Manufacturing Practice (GMP).
Control of Labelling & Packaging:
Current and correct information must be present on medicinal product labelling and packaging to ensure safe and effective use and prescribing.
Supply & Distribution to the Customer:
A safe, controlled and compliant supply-chain from the raw material to the finished medicinal product reaching the customer must be managed and guaranteed by the MAH.
Complaints, Recalls & Quality Defects:
The MAH is obliged to ensure that all medicinal product complaints and quality defects are appropriately investigated. Certain quality defects are reportable to the relevant competent authorities. The MAH, working in conjunction with the competent authority, co-ordinates product recall or further market actions if required.
Pharmacovigilance & appointment of the QPPV:
MAH’s are required to operate a pharmacovigilance system to detect, assess and report adverse events associated with their medicinal products. The pharmacovigilance system should be regularly monitored to ensure compliance with regulatory obligations. All adverse events must be reported in accordance with national and international legislation and relevant guidance to the national competent authority. The MAH is responsible to appoint and have at its disposal permanently and continuously, a qualified person for pharmacovigilance (QPPV) who is responsible for the maintenance of the MAH’s pharmacovigilance system.
Provision of Medical Information:
The timely and regular provision of new and revised medical information to medical information staff is the responsibility of the MAH. Consideration must be given by the MAH to the qualifications and training of medical information staff as well as their access to SPCs.
Control of Responsible Marketing and Promotion:
Promotional activities, including advertising, must comply with the Control of Advertising Regulations, 2007, (S.I. No. 541). Activities must also comply with EU and local codes of practice for the pharmaceutical industry. The MAH must ensure that sales and marketing staff have knowledge of the main aspects of the advertising regulations and that sales representatives have knowledge of the significant elements of the SPCs related to the products which they are promoting. Medicinal product packaging must comply with legislation in relation to requirements for braille and appropriate patient information leaflet formats must be available for partially sighted patients.
Continuity of Supply:
It is the responsibility of the MAH to maintain a continuous supply of the medicinal product to ensure that patient needs are covered. The MAH must notify the relevant competent authority of any medicinal product shortages or disruption of supply.
Take Account of Technical and Scientific Progress:
EU guidance requires the MAH to maintain their marketing authorisations according to technical and scientific developments.
Liaison between MAH’s and Manufacturers:
Additional challenges may exist where the MAH and manufacturer are different companies. However, as MAH you must not forget to:
- Evaluate the results of Product Quality Review Reports
- Communicate regulatory changes to manufacturers, e.g. variation approvals
- Provide abbreviated versions of MA’s to the QP certifying batches of medicinal products
- Regularly review Technical Agreements with manufacturers to ensure their accuracy.
In conclusion, note that some or all of the above activities may be delegated, but the responsibility remains with the MAH.
Source: by Jane Lyons
