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MAH maintenance, Life-cycle-management
MA maintenance and life cycle management of a medicinal product, both, refer to the period starting from the product’s first marketing authorisation and launch into the market until its final withdrawal. During this period, products that have been put on the market change over time and this process must be managed.
It is the responsibility of the marketing authorisation holder (MAH) to update the marketing authorisation granted for its medicinal product as new data emerges. Life cycle management is essential to ensure a constant quality of the product and to guarantee a safe and effective product for patients. This is particularly important for new information that could affect the risk-benefit balance of the medicinal product.
There are several reasons for which post-approval changes are required. It could be either to meet the latest regulatory requirements, to take into account the technical progress, to adapt the product information based on the post-market surveillance information or based on new emerging efficacy data. Therefore, the quality, safety, as well as the efficacy aspects of a medicinal product are subject to change during its life cycle.
Regarding the quality aspect, amendments can be needed following process optimisation or improvements, incorporation of new technologies at the manufacturing site level or following business reasons such as supply issues. Typical post-approval changes affecting the quality of a medicinal products are: changes in the manufacturing site, changes in the manufacturing process, changes in specifications or in analytical procedures, changes in container closure, and changes in shelf-life for active substances or finished products.
Regarding the safety aspect, amendments may be required in the product information following the results of post-marketing surveillance (pharmacovigilance or risk-management plan) of the medicinal product (see also “Pharmacovigilance: Marketing Authorisation” article). Typical post-approval changes affecting the safety of medicinal products could be: addition of precautionary statements, new side-effects, or contraindications.
Regarding the efficacy aspect, amendments may be made following additional clinical investigations on the medicinal product performed to, for example, fulfill a market demand. Typical post-approval changes affecting the efficacy of a medicinal product could be: the addition of a new therapeutic indication, addition of a new strength or change in the dosing regimen.
All these changes impact the content of the documentation submitted to Health Authorities to support an existing marketing authorisation. The MAH will need to submit a variation application to amend the approved registration dossier.
In Europe, Commission Regulation (EC) No 1234/2008 provides the legal basis for the examination of variations to the terms of marketing authorisation for medicinal products. The European Commission has also published guidelines covering the classification of variations, the procedures, and documentation requirements to help the MAH in the submission of variation applications (see also “Variations, renewals and MA transfer” article).
At an international level, the concept of life cycle management is covered by the recent ICH guideline Q12, establishing fundamental tools to support harmonised life cycle management of medicinal products.