SFDA item 15 · II. Quality changes · II.1 Active substance b) Control of active substance
Change in test procedure for active substance or starting material/reagent/intermediate 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 15 — official PDF, p. 23 ↗
| Variant | Change | Type |
|---|---|---|
| a | Minor changes to an approved test procedure | Type IA |
| b | Change (including replacement or addition) to a biological/immunological/immunochemical test method or a method using a biological reagent for a biological active substance. | Type II |
| c | Other changes to a test procedure (including replacement or addition) for the active substance or a starting material/intermediate | Type IB |
| d | Other changes to a test procedure (including replacement or addition) for a reagent, which does not have a significant effect on the overall quality of the active substance | Type IA |
| e | Deletion of a test procedure for the active substance or a starting material/intermediate, if an alternative test procedure is already authorized | Type IA |
Conditions to be fulfilled and documentation to be supplied: see the official guideline, item 15.
EU European Union
Commission Guidelines C/2025/5045 — EUR-Lex ↗
Q.I.b.2 · Change to analytical procedure for active substance or starting material/reagent/intermediate used in the manufacturing process of the active substance
| Variant | Change | Type |
|---|---|---|
| a | Minor change to an analytical procedure for the active substance | Type IA |
| b | Deletion of an analytical procedure for the active substance if an alternative procedure is already authorised | Type IA |
| c | Introduction, replacement or substantial change to a biological/immunological/immunochemical analytical procedure for an active substance | Type II |
| d | Other change to an analytical procedure (including replacement or addition) for the active substance | Type IB |
| e | Minor change to an analytical procedure for starting material/reagent/intermediate | Type IA |
| f | Deletion of an analytical procedure for a starting material/reagent/intermediate, if an alternative analytical procedure is already authorised | Type IA |
| g | Introduction, replacement or change to a biological/immunological/immunochemical analytical procedure for starting material /reagent /intermediate, used in the manufacturing process of an active substance | Type IB |
| h | Other change to an analytical procedure (including replacement or addition) for a starting material/reagent/intermediate | Type IA |
US FDA US Food and Drug Administration
21 CFR 314.70 and FDA guidance — 2004 Guidance §VIII.B.3–5, §VIII.C.1.a, §VIII.C.2.b, §VIII.D.2, §VIII.D.4 · 2014 AR Guidance App. A 4.3
| Change | Category | Reference |
|---|---|---|
| Minor revision of an approved procedure that keeps the methodology and acceptance criteria (e.g., HPLC flow rate, sample preparation) | Annual report | 2014 App. A 4.3 |
| Procedure change for reagents, raw materials, early starting materials or non-final intermediates with equal or greater assurance; adding, revising or deleting an alternative procedure | Annual report | 2004 §VIII.D.4, §VIII.D.2 |
| Procedure change for the final intermediate or later starting materials with equal or greater assurance | CBE-0 supplement | 2004 §VIII.C.2.b |
| Any other change to the drug substance regulatory analytical procedure (not major, not editorial) | CBE-30 supplement | 2004 §VIII.C.1.a |
| New regulatory procedure (incl. making an alternative the regulatory one), or a change that lowers assurance | Prior approval supplement | 2004 §VIII.B.3–5 |
Note: Deleting the regulatory procedure in favour of an approved alternative makes that alternative the regulatory procedure, which is PAS (§VIII.B.3). Deleting only an alternative procedure is AR (§VIII.D.2). Procedure changes for raw materials or early intermediates that lower assurance are CBE-30 (§VIII.C.1.c). Biological assays for protein substances follow BLA rules (21 CFR 601.12).
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.