SFDA item 12 · II. Quality changes · II.1 Active substance a) Manufacture
Change to in-process tests or limits applied during the manufacture 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 12 — official PDF, p. 20 ↗
| Variant | Change | Type |
|---|---|---|
| a | Tightening of in-process limits | Type IA |
| b | Addition of a new in-process test and limits | Type IA |
| c | Widening of the approved in-process control (IPC) limits, which may have a significant effect on the overall quality of the active substance | Type II |
| d | Deletion of an in-process test which may have a significant effect on the overall quality of the active substance | Type II |
| e | Addition or replacement of an in-process test as a result of a safety or quality issue | Type IB |
| f | Deletion of a non-significant in-process test | Type IA |
Conditions to be fulfilled and documentation to be supplied: see the official guideline, item 12.
EU European Union
Commission Guidelines C/2025/5045 — EUR-Lex ↗
Q.I.a.4 · Change to in-process controls applied during the manufacture of the active substance, intermediate of an active substance or starting materials for biological active substance
| Variant | Change | Type |
|---|---|---|
| a | Minor change of in-process control limits | Type IA |
| b | Addition of new in-process control and limits with its corresponding analytical procedure | Type IA |
| c | Deletion of a non-significant or obsolete in-process control | Type IA |
| d | Widening of the approved in-process control limits, which may have a significant effect on the overall quality of the active substance | Type II |
| e | Deletion of an in-process test which may have a significant effect on the overall quality of the active substance | Type II |
| f | Change of an analytical procedure for an in-process control | Type IA |
| g | Replacement of an in-process control 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 4.5, 4.9 · 21 CFR 314.70(b)(2)(i)
| Change | Category | Reference |
|---|---|---|
| Tightening an in-process acceptance criterion | Annual report | 2014 App. A 4.9; 2004 §VIII.D.3 |
| Adding a new in-process test | Annual report | 2014 App. A 4.5 |
| Replacing the in-process procedure for material after the final intermediate with one of equal or greater assurance | CBE-0 supplement | 2004 §VIII.C.2.b |
| Relaxing or deleting an in-process test or limit for material before the final intermediate | CBE-30 supplement | 2004 §VIII.C.1.b |
| Relaxing or deleting an in-process test or limit at or after the final intermediate | Prior approval supplement | 2004 §VIII.B.1–2; 21 CFR 314.70(b)(2)(i) |
Note: FDA has no annual-report route for deleting an in-process test, however minor: deletion is CBE-30 before the final intermediate (§VIII.C.1.b) and PAS at or after it (§VIII.B.2). Replacing a procedure for material before the final intermediate with one of equal or greater assurance is AR (§VIII.D.4).
Other items in II.1 Active substance a) Manufacture
- 9 · 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
- 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
- 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.