This is an archived version. Please see the current version here: Q. QUALITY CHANGES – Q.I ACTIVE SUBSTANCE – Q.I.c) Container closure system
B.I.c.1 Change in immediate packaging of the active substance
B.I.c.3 Change in test procedure for the immediate packaging of the active substance
#bic1
| B.I.c.1 Change in immediate packaging of the active substance | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) Qualitative and/or quantitative composition | 1, 2, 3 | 1, 2, 3, 4, 6 | IA |
| b) Qualitative and/or quantitative composition for sterile and non-frozen biological/immunological active substances | II | ||
| c) Liquid active substances (non sterile) | 1, 2, 3, 5, 6 | IB | |
| Conditions | |||
| 1. The proposed packaging material must be at least equivalent to the approved material in respect of its relevant properties. | |||
| 2. Relevant stability studies have been started under ICH/VICH conditions and relevant stability parameters have been assessed in at least two pilot scale or industrial scale batches and at least three months satisfactory stability data are at the disposal of the applicant at time of implementation. However, if the proposed packaging is more resistant than the existing packaging, the three months’ stability data do not yet have to be available. These studies must be finalised and the data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the shelf-life/retest period (with proposed action). | |||
| 3. Sterile, liquid and biological/immunological active substances are excluded. | |||
| 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). | |||
| 2. Appropriate data on the new packaging (e.g. comparative data on permeability e.g. for O2, CO2 moisture), including a confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic materials and objects in contact with foodstuffs. | |||
| 3. Where appropriate, proof must be provided that no interaction between the content and the packaging material occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeia requirements or legislation of the Union on plastic material and objects in contact with foodstuffs. | |||
| 4. A declaration from the marketing authorisation holder or the ASMF holder as appropriate that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. Assurance should also be given that the 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). | |||
| 5. The results of stability studies that have been carried out under ICH/VICH 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 retest period (with proposed action). | |||
| 6. Comparison of the current and proposed immediate packaging specifications, if applicable. | |||
#bic2
| B.I.c.2 Change in the specification parameters and/or limits of the immediate packaging of the active substance | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) Tightening of specification limits | 1, 2, 3, 4 | 1, 2 | IA |
| b) Addition of a new specification parameter to the specification with its corresponding test method | 1, 2, 5 | 1, 2, 3, 4, 6 | IA |
| c) Deletion of a non-significant specification parameter (e.g. deletion of an obsolete parameter) | 1, 2 | 1, 2, 5 | IA |
| d) Addition or replacement of a specification parameter as a result of a safety or quality issue | 1, 2, 3, 4, 6 | IB | |
| Conditions | |||
| 1. The change is not a consequence of any commitment from previous assessments to review specification limits (e.g. made during the procedure for the marketing authorisation application or a type II variation procedure) unless it has been previously assessed and agreed as part of a follow-up measure. | |||
| 2. The change does not result from unexpected events arising during manufacture of the packaging material or during storage of the active substance. | |||
| 3. Any change should be within the range of currently approved limits. | |||
| 4. The test procedure remains the same, or changes in the test procedure are minor. | |||
| 5. Any new test method does not concern a novel non-standard technique or a standard technique used in a novel way. | |||
| 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). | |||
| 2. Comparative table of current and proposed specifications. | |||
| 3. Details of any new analytical method and validation data, where relevant. | |||
| 4. Batch analysis data on two batches of the immediate packaging for all specification parameters. | |||
| 5. Justification/risk assessment from the marketing authorisation holder or the ASMF Holder, as appropriate, that the in-process parameter is non-significant, or that the in-process parameter is obsolete. | |||
| 6. Justification from the marketing authorisation holder or the ASMF Holder, as appropriate, of the new specification parameter and the limits. | |||
#bic3
| B.I.c.3 Change in test procedure for the immediate packaging of the active substance | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) Minor changes to an approved test procedure | 1, 2, 3, | 1, 2 | IA |
| b) Other changes to a test procedure (including replacement or addition) | 1, 3, 4 | 1, 2 | IA |
| c) Deletion of a test procedure if an alternative test procedure is already authorised | 5 | 1 | IA |
| Conditions | |||
| 1. Appropriate validation studies have been performed in accordance with the relevant guidelines and show that the updated test procedure is at least equivalent to the former test procedure. | |||
| 2. The method of analysis should remain the same (e.g. a change in column length or temperature, but not a different type of column or method). | |||
| 3. Any new test method does not concern a novel non-standard technique or a standard technique used in a novel way. | |||
| 4. The active substance/ finished product is not biological/immunological. | |||
| 5. There is still a test procedure registered for the specification parameter and this procedure has not been added through a IA/IA(IN) notification. | |||
| 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), including a description of the analytical methodology, a summary of validation data. | |||
| 2. Comparative validation results or if justified comparative analysis results showing that the current test and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new test procedure. | |||