This is an archived version. Please see the current version here: Q. QUALITY CHANGES – Q.I ACTIVE SUBSTANCE – Q.I.e) Additional regulatory tools
B.I.e.2 Introduction of a post approval change management protocol related to the active substance
B.I.e.3 Deletion of an approved change management protocol related to the active substance
B.I.e.4 Changes to an approved change management protocol
B.I.e.5 Implementation of changes foreseen in an approved change management protocol
#bie1
| B.I.e.1 Introduction of a new design space or extension of an approved design space for the active substance, concerning: | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) One unit operation in the manufacturing process of the active substance including the resulting in- process controls and/or test procedures | 1, 2, 3 | II | |
| b) Test procedures for starting materials/reagents/ intermediates and/or the active substance | 1, 2, 3 | II | |
| Documentation | |||
| 1. The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies (e.g. interaction of the different parameters forming the design space have to be studied, including risk assessment and multivariate studies, as appropriate) demonstrating where relevant that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the active substance has been achieved. | |||
| 2. Description of the Design space in tabular format, including the variables (material attributes and process parameters, as appropriate) and their proposed ranges. | |||
| 3. 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). | |||
#bie2
| B.I.e.2 Introduction of a post approval change management protocol related to the active substance | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| 1, 2, 3 | II | ||
| Documentation | |||
| 1. Detailed description for the proposed change. | |||
| 2. Change management protocol related to the active substance. | |||
| 3. 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). | |||
#bie3
| B.I.e.3 Deletion of an approved change management protocol related to the active substance | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| 1 | 1, 2 | IAIN | |
| Conditions | |||
| 1. The deletion of the approved change management protocol related to the active substance is not a result of unexpected events or out of specification results during the implementation of the change (s) described in the protocol and does not have any effect on the already approved information in the dossier. | |||
| Documentation | |||
| 1. Justification for the proposed deletion. | |||
| 2. 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). | |||
#bie4
| B.I.e.4 Changes to an approved change management protocol | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) Major changes to an approved change management protocol | II | ||
| b) Minor changes to an approved change management protocol that do not change the strategy defined in the protocol | 1 | IB | |
| Documentation | |||
| 1. Declaration that any change should be within the range of currently approved limits. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. | |||
#bie5
| B.I.e.5 Implementation of changes foreseen in an approved change management protocol | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) The implementation of the change requires no further supportive data | 1 | 1, 2, 4 | IAIN |
| b) The implementation of the change requires further supportive data | 1, 2, 3, 4 | IB | |
| c) Implementation of a change for a biological/immunological medicinal product | 1, 2, 3, 4, 5 | IB | |
| Conditions | |||
| 1. The proposed change has been performed fully in line with the approved change management protocol. | |||
| Documentation | |||
| 1. Reference to the approved change management protocol. | |||
| 2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. | |||
| 3. Results of the studies performed in accordance with the approved change management protocol. | |||
| 4. 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). | |||
| 5. Copy of approved specifications of the active substance. | |||