SFDA item 14 · II. Quality changes · II.1 Active substance b) Control of active substance
Change in the specification parameters and/or limits of an active substance, starting material/intermediate/reagent used in the manufacturing process of the active substance
Variation category under SFDA, EU and US FDA rules for this change, with the variant wording as published.
SFDA Saudi Food and Drug Authority
Guidelines for Variation Requirements v6.3 (DS-G-006), item 14 — official PDF, p. 22 ↗
| Variant | Change | Type |
|---|---|---|
| a | Tightening of specification limits | Type IA(IN) |
| b | Addition of a new specification parameter to the specification with its corresponding test method | Type IA |
| c | Change outside the approved specifications limits range for the active substance | Type II |
| d | Widening of the approved specifications limits for starting materials/reagents/intermediates, which may have a significant effect on the overall quality of the active substance and/or the finished product | Type II |
| e | Deletion of a specification parameter which may have a significant effect on the overall quality of the active substance and/or the finished product | Type II |
| f | Addition or replacement (excluding biological or immunological substance) of a specification parameter as a result of a safety or quality issue | Type IB |
| g | Deletion of a non-significant specification parameter (e.g. deletion of an obsolete parameter) | Type IA |
| h | a change in specification from in-house to a non-official Pharmacopoeia | Type IB |
Conditions to be fulfilled and documentation to be supplied: see the official guideline, item 14.
EU European Union
Commission Guidelines C/2025/5045 — EUR-Lex ↗
Q.I.b.1 · Change in the specification attribute and/or acceptance criteria of an active substance, starting material/reagent/intermediate used in the manufacturing process of the active substance
| Variant | Change | Type |
|---|---|---|
| a | Change within the specification acceptance criteria for finished product subject to Official Control Authority Batch Release | Type IA(IN) |
| b | Change within the specification acceptance criteria | Type IA |
| c | Addition of a new specification attribute with its corresponding analytical procedure and acceptance criteria | Type IA |
| d | Deletion of a non-significant or an obsolete specification attribute | Type IA |
| e | Deletion of a specification attribute which may have a significant effect on the overall quality of the active substance and/or the finished product | Type II |
| f | Change outside of the specification acceptance criteria for the active substance | Type II |
| g | Change outside of the specification acceptance criteria for starting material/reagent/intermediate which may have a significant effect on the overall quality of the active substance and/or the finished product | Type II |
| h | Change outside of the specification acceptance criteria for starting material/reagent/intermediate | Type IB |
| i | Change in specification attribute for the active substance from in-house to a non-official Pharmacopoeia/Pharmacopoeia of a third country where there is no monograph in the European Pharmacopoeia or the national pharmacopoeia of a Member State | Type IB |
| j | Change of the analytical marker or widening of the acceptance criteria of the analytical marker (other extracts) for a herbal active substance | Type IB |
| k | Change in the testing of specification attribute of the active substance, from routine to skip/periodic testing and vice versa | Type IB |
| l | Replacement of a specification attribute with its corresponding analytical procedure | Type IB |
US FDA US Food and Drug Administration
21 CFR 314.70 and FDA guidance — 2004 Guidance §VIII.B–D · 2014 AR Guidance App. A 4.9 · 21 CFR 314.70(b)(2)(i), (c)(6)(i)
| Change | Category | Reference |
|---|---|---|
| Tightening an acceptance criterion | Annual report | 2014 App. A 4.9; 2004 §VIII.D.3 |
| Adding a new test with its procedure and acceptance criterion | CBE-0 supplement | 2004 §VIII.C.2.a; 21 CFR 314.70(c)(6)(i) |
| Relaxing or deleting a test for raw materials, starting materials or intermediates before the final intermediate | CBE-30 supplement | 2004 §VIII.C.1.b |
| Relaxing or deleting a test for the drug substance or final intermediate | Prior approval supplement | 2004 §VIII.B.1–2; 21 CFR 314.70(b)(2)(i) |
Note: Relaxing or deleting a test to comply with USP/NF is CBE-30 (314.70(c)(2)(iii)); other compendial alignment is AR (2014 App. A 4.2). The official compendium is USP/NF, so adopting another pharmacopoeia is assessed test by test. Deleting an obsolete drug substance test has no annual-report route (PAS, §VIII.B.2).
Other items in II.1 Active substance b) Control of active substance
Not regulatory advice. The binding text is each regulator's current official document; confirm the category with the authority before filing. FDA publishes no classification table: the US category follows FDA guidance or, where the guidance does not name the change, the closest example under 21 CFR 314.70.