Frequently asked questions (FAQ)

Answer: The requirements stipulated by Article 78 are applicable to type IB and type II variations to marketing authorisation documentation, as classified according to the European Commission Regulation (EC) No. 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (hereinafter – Regulation 1234/2008) and European Commission Guidelines No. 2013/C 223/01 “Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No. 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures”.

Requirements pursuant to Article 78 are not applicable to:

• Type IA variations to marketing authorisation documentation as they are so called “do and tell” variations according to Regulation 1234/2008 which the marketing authorisation holder introduces first and only then notifies the competent authority;
• Change of marketing authorization holder (hereinafter – MAH). Change of MAH is not subjected to the requirements of Regulation 1234/2008. Requirements for change of MAH are stipulated by Article 82 of the Cabinet of Ministers regulation No. 376 of 9 May 2006 “Procedures for the Registration of Medicinal Products”. Upon submission of application for change of MAH, the date when the person applying for the issuance of a marketing authorisation takes over the responsibilities of the previous marketing authorisation holder must be indicated. After MAH change approval, information on product information about manufacturing of the medicinal product should start in next 6 months or with next manufacturing of the product series, in case manufacturing is not planned in 6 months after MAH change approval.

Answer: During the time period from approval of variations until the implementation of variations indicated in the application form medicines may be manufactured* and their series may be released pursuant to the previously approved marketing authorisation documentation, except situations described in Subparagraphs 78.1 and 78.2 of Regulation No. 416.

Example 1. For type IB variations, to extend the storage time of a medicinal product from 2 to 3 years, the date of variation implementation is indicated in the application form as “within 6 months from variation approval”, e.g., until 15.12.2024. Situations described in Subparagraphs 78.1 and 78.2 are not applicable to this example. The medicinal product with the previously approved marketing authorization documentation, i.e., storage time (2 years), may be manufactured and their series may be released until 14.12.2024.

Example 2. For type IB variations, to decrease storage time from 3 to 2 years due to quality deficiencies (defects) identified, the variations implementation date in the application form is indicated “within 6 months from variation approval”, e.g., it would be until 15.12.2024. Together with the approval of variations, a deadline has been set for distribution of remaining stock of medicinal product. The medicinal product with the previously approved marketing authorisation documentation, i.e., storage time (3 years), may not be manufactured due to the situation described in subparagraph 78.2. Variations with respect to the decreased storage time (i.e., 2 years) must be implemented with the next manufacturing run. Medicinal product series manufactured prior to variation approval may be released, but the deadline for distribution of remaining stock of medicinal product must be followed.

* Explanation regarding the start date for manufacturing of medicinal product series is provided in the guideline CPMP/QWP/072/96 NfG on start of shelf-life of the finished dosage form.

Answer: As the application has been submitted for grouped type IA and IB variations, then this variation group is considered as a type IB variation. Therefore, the updated product information must be implemented starting from 30.11.2024.

** Examples of grouping of type IA and IB variations in a single application are provided in the CMDh (Co-ordination Group for Mutual Recognition and Decentralised procedures - Human) document Examples for acceptable and not acceptable groupings for MRP/DCP products.

Answer: A deadline for distribution of remaining stock of medicinal products is set in cases where the quality, safety and/or effectiveness of medicinal products may be affected. Most frequent examples:

• Decrease of medicinal product storage time and/or narrowing of medicinal product storage conditions (more stringent conditions for medicinal product storage) due to quality concerns (e.g., medicinal product stability, identified impurities, quality defects);
• Substantial changes in drug formulation (contents) and/or resulting substantial changes in medicinal product manufacturing process;
• Change of medicinal product prescription status from non-prescription to prescription medicinal products.

Answer: Distribution of remaining stock of medicinal product is not permitted, if the variation approval entails approval of substantial limitations related to the safe use of medicinal product and they affect the package leaflet. For example:

• Annulment of approved indications;
• Substantial changes in medicinal product dosing;
• Addition of new contraindications;
• Medicinal product use is limited in a particular patient group (in children, pregnant women, special patient groups).

Distribution of remaining stock of medicinal products is also not permitted in cases when urgent limitations related to medicinal product safety, safeguarding of public health are necessary.

Answer: Considering that the Agency has set a deadline for distribution of remaining stock of a medicinal product in its decision regarding annulment of marketing authorisation and withdrawal of the aforementioned medicines from the Medicinal Product Register of Latvia or suspension or annulment of permit for distribution of parallel imported medicines in accordance with the requirements of Article 81 and 81.1, as well as the fact that normative acts do not stipulate an option to distribute remaining stock of medicinal products for more than 6 months after withdrawal of medicines from the Medicinal Product Register of Latvia or annulment of permit for distribution of parallel imported medicines, the Agency has no legal justification to extend the deadline for distribution of remaining stock of medicines.