Variations Guidelines

Guidelines on the details of the various categories of variations

ANNEX

A. Administrative changes

B. Quality changes

B.I ACTIVE SUBSTANCE

B.I.a) Manufacture

B.I.b) Control of active substance

B.I.c) Container closure system

B.I.d) Stability

B.I.e) Design Space and post-approval change management protocols

B.II FINISHED PRODUCT

B.II.a) Description and composition

B.II.b) Manufacture

B.II.c) Control of excipients

B.II.d) Control of finished product

B.II.e) Container closure system

B.II.f) Stability

B.II.g) Design Space and post approval change management protocol

B.II.h) Adventitious Agents Safety

B.III CEP/TSE/Monographs

B.IV Medical Devices

B.V. Changes to a marketing authorisation resulting from other regulatory procedures

B.V.a) PMF/VAMF

B.V.b) Referral

C. Safety, efficacy, pharmacovigilance changes

C.I Human and veterinary medicinal products

C.II Veterinary medicinal product – specific changes

D. PMF / VAMF

Version dated 02.08.2013, includung Addendum to the Variations Guidelines (2021/C 215 I/01).
Current status: Obsolete, superseded by version Variations Guidelines C/2025/5045

B. QUALITY CHANGES – B.II FINISHED PRODUCT – B.II.f) Stability (obsolete version)

This is an archived version. Please see the current version here: Q. QUALITY CHANGES – Q.II. FINISHED PRODUCT – Q.II.f) Stability

B.II.f.1 Change in the shelf-life or storage conditions of the finished product

#biif1

B.II.f.1 Change in the shelf-life or storage conditions of the finished productConditions to be fulfilledDocumentation to be suppliedProcedure type
a) Reduction of the shelf life of the finished product   
1. As packaged for sale11, 2, 3IAIN
2. After first opening11, 2, 3IAIN
3. After dilution or reconstitution11, 2, 3IAIN
b) Extension of the shelf life of the finished product   
1. As packaged for sale (supported by real time data) 1, 2, 3IB
2. After first opening (supported by real time data) 1, 2, 3IB
3. After dilution or reconstitution (supported by real time data) 1, 2, 3IB
4. Extension of the shelf-life based on extrapolation of stability data not in accordance with ICH/VICH guidelines*  II
5. Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol. 1, 2, 3IB
c) Change in storage conditions for biological medicinal products, when the stability studies have not been performed in accordance with an approved stability protocol  II
d) Change in storage conditions of the finished product or the diluted/reconstituted product 1, 2, 3IB
e) Change to an approved stability protocol1, 21, 4IA
Conditions
1. The change should not be the result of unexpected events arising during manufacture or because of stability concerns.
2. The change does not concern a widening of the acceptance criteria in the parameters tested, a removal of stability indicating parameters or a reduction in the frequency of testing.
Documentation
1. Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate). This must contain results of appropriate real time stability studies (covering the entire shelf life) conducted in accordance with the relevant stability guidelines on at least two pilot scale batches1 of the finished product in the authorised packaging material and/or after first opening or reconstitution, as appropriate; where applicable, results of appropriate microbiological testing should be included.
1Pilot scale batches can be accepted with a commitment to verify the shelf life on production scale batches.
2. Revised product information
3. Copy of approved end of shelf life finished product specification and where applicable, specifications after dilution/reconstitution or first opening.
4. Justification for the proposed change(s).
*Note: extrapolation not applicable for biological/immunological medicinal product.