SFDA item 9 · II. Quality changes · II.1 Active substance a) Manufacture
Change in the manufacturer of a starting material/reagent/intermediate used in the manufacturing process of the active substance or change in the manufacturer of the active substance, where no Certificate of Suitability is available
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 9 — official PDF, p. 16 ↗
| Variant | Change | Type |
|---|---|---|
| a | The proposed manufacturer is part of the same organization as the currently approved manufacturer. | Type IA(IN) |
| b | Introduction of a manufacturer of the active substance supported by a DMF. | Type II |
| c | The proposed manufacturer uses a substantially different route of synthesis or manufacturing conditions, which may have a potential to change important quality characteristics of the active substance, such as qualitative and/or quantitative impurity profile requiring qualification, or physico-chemical properties impacting on bioavailability. | Type II |
| d | New manufacturer of material for which an assessment is required of viral safety and/or TSE risk | Type II |
| e | The change relates to a biological active substance or a starting material/reagent/intermediate used in the manufacture of a biological/immunological product | Type II |
| f | Changes to quality control testing arrangements for the active substance-replacement or addition of a site where batch control/testing takes place | Type IA |
| g | Addition of an alternative sterilization site for the active substance using a pharmacopeial method | Type IB |
| h | Introduction of a new manufacturer of the active substance that is not supported by a DMF and requires significant update to the relevant active substance section of the dossier. | Type II |
| i | Introduction of a new site of micronisation | Type IA |
| j | Changes to quality control testing arrangements for a biological active substance: replacement or addition of a site where batch control/testing including a biological/immunological/immunochemical method takes place | Type II |
| k | New storage site of Master Cell Bank and/or Working Cell Banks | Type IB |
| l | Addition/change to an API supplier that has already been approved | Type IA(IN) |
Conditions to be fulfilled and documentation to be supplied: see the official guideline, item 9.
EU European Union
Commission Guidelines C/2025/5045 — EUR-Lex ↗
Q.I.a.1 · Change in the manufacturing site of a starting material/intermediate used in the manufacturing process of the active substance or change in the manufacturing site (including where relevant quality control testing sites) of the active substance
| Variant | Change | Type |
|---|---|---|
| a | Addition or replacement of a manufacturing site of an active substance or intermediate | Type IA(IN) |
| b | Addition or replacement of a manufacturing site of an active substance or intermediate that requires significant update to the relevant active substance section of the dossier, e.g. where a substantially different route of synthesis or manufacturing conditions is used, which may have a potential to change important quality characteristics of the active substance, such as qualitative and/or quantitative impurity profile requiring qualification, or physico-chemical properties impacting on bioavailability | Type II |
| c | Addition or replacement of a manufacturing site of a starting material used in the manufacture of the active substance or reagent required to be mentioned in the dossier | Type IA |
| d | Addition or replacement of a manufacturing site of — a biological active substance or — a biological starting material/reagent/raw material/intermediate used in the manufacture of a biological active substance which may have a significant impact on the quality, safety or efficacy of the finished product or — a material for which an assessment is required of viral safety and/or TSE risk | Type II |
| e | Addition or replacement of a new herbal starting material supplier or of a new herbal active substance manufacturing site using the same or different plant production (i.e. cultivated or wild collection) | Type IB |
| f | Addition of a manufacturing site of the active substance that is supported by an Active Substance Master File (ASMF) | Type II |
| g | Addition or replacement of a manufacturing site responsible for sterilisation of the active substance using a Ph. Eur. method | Type IB |
| h | Addition or replacement of a manufacturing site responsible for micronisation of the active substance | Type IA |
| i | Addition or replacement of a batch control/testing site of the active substance or starting material/intermediate used in the manufacturing of a biological active substance, applying a biological/immunological/immunochemical analytical procedure | Type IB |
| j | Addition or replacement of a batch control/testing site of the — the active substance or — intermediate of an active substance or — starting material of a biological active substance applying physicochemical and/or microbiological analytical procedures | Type IA |
| k | Addition or replacement of a storage site of the Master Cell Bank and/or Working Cell Banks | Type IA |
US FDA US Food and Drug Administration
21 CFR 314.70 and FDA guidance — 2004 Guidance §VI (Manufacturing Sites), §VII.B.3–5 · 21 CFR 314.70(b)(2)(iv), (c)(1), (d)(1)
| Change | Category | Reference |
|---|---|---|
| New or alternate site making a drug substance intermediate other than the final intermediate | Annual report | 2004 §VI.D.3 |
| New or alternate site making the final intermediate | CBE-0 supplement | 2004 §VI.C.2 |
| New or alternate drug substance manufacturing/processing site (incl. micronisation or contract sterilization), same route, process and specs, satisfactory CGMP status | CBE-30 supplement | 2004 §VI.C.1.a |
| New or alternate drug substance testing site using the approved test procedures | CBE-30 supplement | 2004 §VI.C.1.d |
| New source with a different route of synthesis or a process that may change the impurity profile or physical properties; or any new site without a satisfactory CGMP inspection | Prior approval supplement | 21 CFR 314.70(b)(2)(iv); 2004 §VII.B.4.b, §VI.B.1–2 |
| Natural-product drug substance: new source material, cell line or seed | Prior approval supplement | 2004 §VII.B.3; 21 CFR 314.70(b)(2)(vii) |
Note: The category depends on the operation type and CGMP status, not corporate affiliation. A new site without a satisfactory CGMP inspection is PAS (§VI.B.1–2; intermediate sites excepted). A new API source is usually covered by the supplier's Type II DMF; the supplement is PAS if the route or impurity profile differs. Biological substances and cell-bank sites follow 21 CFR 601.12.
Other items in II.1 Active substance a) Manufacture
- 10 · Changes in the manufacturing process of the active substance
- 11 · Change in batch size (including batch size ranges) of active substance or intermediate used in the manufacturing process of the active substance
- 12 · Change to in-process tests or limits applied during the manufacture of the active substance
- 13 · Changes to the active substance of a seasonal, prepandemic or pandemic vaccine against human influenza
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.