Variations – changes that may take place relevant to an already registered medicine

Changes may be required to the content of particulars related to the medicine that were submitted at the time of applying for registration, due to various reasons such as technical and scientific advances, new findings that affects its quality, safety, efficacy, or simply changes of administrative nature. Marketing authorization holder is legally bound to inform any such changes to the National Medicines Regulatory Authority.

Regulation 16 of the Medicine Regulations No. 2145/1 of 14.10.2019 requires the marketing authorization holder to comply with variation guidelines published by NMRA, and to inform forthwith the following:  

• information received that casts doubt on the continued validity of the data which was submitted with, or in connection with the application for the registration of the medicine;
• decision to withdraw the medicine from Sri Lanka and the reasons for such decision;
• decision not to market any registered medicine; and
• decision to terminate his activities as the holder of certificate.

 For biotherapeutic products and vaccines, the following WHO guidelines apply:

• Guidelines on procedures and data requirements for changes to approved biotherapeutic products, Annex 3, WHO TRS 1011, 2018
• Guidelines on procedures and data requirements for changes to approved vaccines, Annex 4, WHO TRS 993, 2015

For multisource products, ‘Guideline for Variations of Medicines’ published by NMRA applies

Marketing authorization holders for relevant products are required to submit a variation application to NMRA with the prescribed form when there is any material change, procedural change, change to labeling, any other changes that would affect product’s quality, safety, or efficacy.

Variations are categorized as follow;

Major Variations (MAV)
Proposed changes that may affect directly and/or significantly the aspects of its quality, safety and efficacy of a registered medicine and they do not fall within the definition of a minor variation or a new registration. Prior to implementation of such changes, approval of the NMRA is necessary

Minor variations requiring approval (MIV1)
Proposed changes may have minimum impact on the quality, safety, and efficacy of a registered medicine. NMRA approval for the change is still required prior to implementation.

Minor variations requiring notification (MIV2)
These changes are mainly of administrative nature with no significant impact on quality, safety, and efficacy of the registered medicine. Marketing authorization holder requires only notifying the change to the NMRA.