Q.II.d.1 Change in the specification attribute and/or acceptance criteria of the finished product
Q.II.d.2 Change to analytical procedure for the finished product
Q.II.d.3 Variations related to real-time release testing in the manufacture of the finished product
#qiid1
| Q.II.d.1 Change in the specification attribute and/or acceptance criteria of the finished product | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) Change within the specifications acceptance criteria | 1, 2, 4 | 1, 2 | IA |
| (b) Change within the specification acceptance criteria for finished products subject to Official Control Authority Batch Release | 1, 2, 4 | 1, 2 | IAIN |
| (c) Addition of a new specification attribute with its corresponding analytical procedure and acceptance criteria | 1, 2, 5, 6 | 1, 2, 3, 4, 6 | IA |
| (d) Deletion of a non-significant or obsolete specification attribute (e.g. deletion of odour and taste or identification test for a colouring or flavouring material) | 1, 2, 3, 7 | 1, 2, 5 | IA |
| (e) Change outside of the specification acceptance criteria of the finished product | II | ||
| (f) Deletion of a specification attribute which may have a significant effect on the overall quality of the finished product | II | ||
| (g) Update of the dossier to comply with the provisions of an updated general monograph of the Ph. Eur(2). | 1, 2, 4, 6 | 1, 2 | IAIN |
| (h) Ph. Eur. 2.9.40 Uniformity of dosage units is introduced to replace the currently registered method, either Ph. Eur. 2.9.5 (Uniformity of mass) or Ph. Eur. 2.9.6 (Uniformity of content) | 1, 2, 8 | 1, 2, 4 | IA |
| (i) Change in the testing of specification attribute, from routine to skip/periodic testing and vice versa | 1, 2, 7 | IB | |
| (j) Replacement of a specification attribute with its corresponding analytical procedure | 1, 2, 3, 4, 6 | IB | |
| Conditions | |||
| 1. The change is not a consequence of any commitment from previous assessments to review specification acceptance criteria (e.g. made during the procedure for the marketing authorisation application or a Type II variation procedure), unless the supporting documentation has been already assessed and approved within another procedure. | |||
| 2. The change does not result from unexpected events arising during manufacture or because of stability concerns, or as a result of a safety or quality issue, e.g. new unqualified impurity; change in total impurity acceptance criteria. | |||
| 3. The change is not related to a revision of the control strategy with an intention to minimise testing of parameters and attributes (critical or non-critical). | |||
| 4. The analytical procedure remains the same. | |||
| 5. Any new analytical procedure does not concern a novel non-standard technique or a standard technique used in a novel way. | |||
| 6. The change does not concern any impurities (including genotoxic) or dissolution. | |||
| 7. The specification attribute or proposal for the specific dosage form does not concern a critical attribute, for example: – identity, – assay, – purity, – impurities (except solvent is not used in the manufacture of the finished product), – critical physical characteristics (for example: hardness or friability for uncoated tablets, dimensions) – a test that is required for the particular dosage form in accordance with the general notices of the Ph. Eur., – any request for skip testing. | |||
| 8. The proposed control is fully in line with the Table 2.9.40.-1 of Ph. Eur. 2.9.40 monograph, and does not include the alternative proposal for testing uniformity of dosage units by Mass Variation instead of Content Uniformity when the latter is specified in Table 2.9.40.-1. | |||
| Documentation | |||
| 1. Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). | |||
| 2. Comparative table of current and proposed specifications. | |||
| 3. Details of any new analytical procedure and validation data, where relevant. | |||
| 4. Batch analysis data on two production batches (3 production batches (unless otherwise justified) for biologicals) of the finished product for all specification attributes. | |||
| 5. Justification/risk assessment showing that the attribute is non-significant or that it is obsolete. | |||
| 6. Justification of the new specification attribute and the acceptance criteria. | |||
| (2) Note: Upon approval of the variation for the qualification protocol, the introduction of a new reference standard for a biological active substance/finished product or the extension of its re-test period/storage period, according to the approved qualification protocol will be covered by the existing quality assurance system and hence, there will be no need to file a variation as long as all approved acceptance criteria are met. | |||
#qiid2
| Q.II.d.2 Change to analytical procedure for the finished product | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) Minor change to an approved analytical procedure | 1, 2, 3 | 1, 2 | IA |
| (b) Deletion of an analytical procedure if an alternative procedure is already authorised | 4 | 1 | IA |
| (c) Introduction, replacement, or substantial change to a biological/immunological/immunochemical analytical procedure for a finished product | II | ||
| (d) Other change to an analytical procedure for a finished product (including replacement or addition) | 1, 2 | IB | |
| (e) Update of the analytical procedure to comply with the updated general monograph in the Ph. Eur. | 2, 3, 5, 6 | 1 | IA |
| (f) To reflect compliance with the Ph. Eur. and remove reference to the outdated internal analytical procedure and analytical procedure number | 2, 3, 5, 6 | 1 | IA |
| Conditions | |||
| 1. 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 procedure. | |||
| 2. There have been no changes of the total impurity limits; no new unqualified impurities are detected. | |||
| 3. 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). | |||
| 4. An alternative analytical procedure is already authorised for the specification attribute. | |||
| 5. The registered analytical procedure already refers to the general monograph of the Ph. Eur. and any changes are minor in nature and require update of the technical dossier. | |||
| 6. The analytical procedure is not a biological/immunological/immunochemical procedure. | |||
| Documentation | |||
| 1. Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a description of the analytical methodology, a summary of validation data, revised specifications. | |||
| 2. 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 unless the new analytical procedure is added as an alternative procedure to a current one. | |||
#qiid3
| Q.II.d.3 Variations related to real-time release testing in the manufacture of the finished product | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| Introduction, replacement, or substantial change of a real-time release testing procedure | II | ||
| Note: For changes to in-house reference standard/preparation for a biological finished product, refer to category Q.I.b.3 Change to an in-house reference standard/preparation for a biological active substance. | |||
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