Q.IV Medical devices

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Valid Version — C/2025/5045 (effective 16.01.2026)

Previous version is available here: Variations Guidelines 2013/C 223/01

Note: changes to medical devices should be submitted under the appropriate Q.IV classification, even if the medical device also acts as container closure system.

Q.IV.1 Changes to a device co-packaged with the medicinal product or referenced in the product information

Q.IV.2 Changes to an integral medical device (part)

Q.IV.3 Changes to the dimensions, specification attributes and/or acceptance criteria or analytical procedures for an integral medical device (part)

#qiv1

Q.IV.1 Changes to a device co-packaged with the medicinal product or referenced in the product information	Conditions to be fulfilled	Documentation to be supplied	Procedure type
(a) Addition or replacement of a co-packaged device or referenced device	1, 2, 3, 5	1, 2, 3	IA_IN
(b) Addition, replacement or other changes of a co-packaged or referenced device that may have a significant impact to the delivery, quality, safety and/or efficacy of the medicinal product			II
(c) Deletion of a co-packaged or referenced device	3, 4, 5	1, 4	IA_IN
(d) Minor change for a co-packaged device or referenced device that does not impact the delivery, quality, safety and/or efficacy of the medicinal product or the usability of the device	3, 5	1	IA
Conditions
1. The change does not have a significant impact on the delivery, quality, safety and/or efficacy of the medicinal product or the usability of the device.
2. Compatibility studies have been finalised and the device is compatible with the medicinal product.
3. The change should not lead to substantial amendments of the product information.
4. The medicinal product can still be safely and accurately delivered.
5. There is no impact to the Risk Management Plan of the medicinal product.
Documentation
1. Amendment of the relevant section(s) of the dossier, including description, drawing and composition of the device material, compatibility and usability studies as appropriate.
2. For the addition or replacement of a co-packaged medical device, evidence that relevant standards have been met e.g. EU declaration of conformity or, where applicable, EU certificate, or other appropriate documentation such as summary information confirming compliance with relevant General Safety and Performance Requirements.
3. Data to demonstrate performance, safety and compatibility of the device, as appropriate.
4. Justification for the deletion of the device.

#qiv2

Q.IV.2 Changes to an integral medical device (part)	Conditions to be fulfilled	Documentation to be supplied	Procedure type
(a) Addition or replacement of an integral device (part) or major change to the materials and/or design and/or performance characteristics of an integral device which may have a significant impact on the delivery or the quality, safety, or efficacy of the medicinal product			II
(b) Addition or replacement of an integral device (part) which does not have a significant impact on the performance, delivery, quality, safety or efficacy of the medicinal product		1, 2	IB
(c) Deletion of an integral medical device (part) that does not lead to the complete deletion of a strength or pharmaceutical form	1, 2	1	IA_IN
(d) Change of a material of a device (part) not in contact with the medicinal product	3, 4	1, 2	IA
(e) Change of a material of a device (part) in contact with the medicinal product that does not have a significant impact on the performance, safety, quality or efficacy of the medicinal product and does not contain materials of human or animal origin for which assessment is required of viral safety data or TSE risk		1, 2, 3, 4	IB
(f) Addition or replacement of a supplier/manufacturer of an existing device (part)	5, 6	1, 2	IA
(g) Addition or replacement of a site responsible for sterilisation of the device (part) and/or change to the sterilisation process of the device (part) when supplied as sterile		1, 2, 5, 6	IB
(h) Other minor change to an integral device (part)	3, 4	1, 2	IA
Conditions
1. The medicinal product can still be safely and accurately delivered.
2. The remaining product presentation(s) must be adequate for the dosing instructions and treatment duration as mentioned in the summary of product characteristics.
3. The change has no impact on the performance, delivery, safety or quality of the finished product. The functionality must remain the same.
4. There is no substantial amendment of the product information.
5. There is no change to the device (part).
6. The supplier/manufacturer does not perform sterilisation.
Documentation
1. Amendment of the relevant section(s) of the dossier, including revised product information as appropriate.
2. Justification for the absence of a Notified Body opinion/EU certificate/EU declaration of conformity, based on the risk-assessment performed, which concluded that the proposed change has no significant impact on the medicinal product.
3. The results of stability studies that have been carried out under ICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action).
4. Where appropriate, proof must be provided that no interaction between the medicinal product and the device (part) occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the device), including confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic material and objects in contact with foodstuffs. Comparative data on permeability e.g. for O₂, CO₂ moisture should be provided as appropriate.
5. Evidence that the sterilisation has been conducted and validated in accordance with GMP and/or relevant ISO standards, as per guideline on the sterilisation of the medicinal product, active substance, excipient and primary container.
6. Description of the sterilisation method and sterilisation cycle. Validation of the sterilisation cycle should be provided if it does not use the reference conditions stated in Ph. Eur..

#qiv3

Q.IV.3 Changes to the dimensions, specification attributes and/or acceptance criteria or analytical procedures for an integral medical device (part)	Conditions to be fulfilled	Documentation to be supplied	Procedure type
(a) Minor change to the dimensions of a medical device (part)	1, 2, 3	1	IA
(b) Change to the specification for a medical device (part) that is not part of the final product specifications
1. Change to the specification acceptance criteria, including amendments to more accurately describe the appearance	1, 2, 4, 5	1	IA
2. Addition of a new specification attribute with its corresponding analytical procedure	1, 2, 8	1, 2, 3	IA
3. Replacement of a specification attribute with its corresponding analytical procedure		1, 2, 3	IB
4. Change outside of a specification acceptance criteria or deletion of a specification attribute that has a significant impact on the quality, safety, performance or usability of the device			II
(c) Change to an analytical procedure for the medical device (part)
1. Addition, replacement or other change to an approved analytical procedure	1, 6	1, 2, 4	IA
2. Deletion of an analytical procedure if an alternative an analytical procedure is already authorised	1, 7	1	IA
Conditions
1. The change does not impact the delivery, use, safety or stability of the finished product.
2. No change in the qualitative or quantitative composition of the device (part).
3. No change in the headspace or in the surface/volume ratio, or minor changes that do not impact the stability of the final product.
4. The change should be in the range of currently approved specification acceptance criteria.
5. The analytical procedure remains the same or changes to the analytical procedure are minor.
6. Appropriate validation studies have been performed in accordance with the relevant guidelines and show that the updated analytical procedure is at least equivalent to the former analytical procedure (when appropriate).
7. An alternative analytical procedure is already authorised for the specification attribute.
8. The change is not the result of a safety or quality issue.
Documentation
1. Amendment of the relevant section(s) of the dossier.
2. Details of any new analytical procedure and validation, where relevant.
3. Justification of the specification attribute and its acceptance criteria.
4. Comparative validation results or if justified comparative analysis results showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure.
Note: Q.IV.3 classification applicable to specifications and analytical procedures for the medical device (part) only (3.2.P.7). Analytical procedures and specifications that are part of the final product specification and control strategy (3.2.P.5) should be classified under the appropriate Q.II category.

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