SFDA item 35 · II. Quality changes · II.2 Finished product c) Control of excipients
Change in synthesis or recovery of a non-pharmacopeial excipient (when described in the dossier) or a novel excipient
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 35 — official PDF, p. 45 ↗
| Variant | Change | Type |
|---|---|---|
| a | Minor change in synthesis or recovery of a non-pharmacopeial excipient or a novel excipient | Type IA |
| b | The specifications are affected or there is a change in physicochemical properties of the excipient which may affect the quality of the finished product. | Type II |
| c | The excipient is a biological/immunological substance | Type II |
Conditions to be fulfilled and documentation to be supplied: see the official guideline, item 35.
EU European Union
Commission Guidelines C/2025/5045 — EUR-Lex ↗
Q.II.c.4 · Change in synthesis, manufacturing or recovery of an excipient (when described in the dossier)
| Variant | Change | Type |
|---|---|---|
| a | Minor change in synthesis, manufacturing or recovery of an excipient | Type IA |
| b | Change in the manufacturing site, synthesis, manufacturing or recovery of the excipient which may affect the quality, safety or efficacy of the finished product | Type II |
| c | Deletion of one manufacturing process of an excipient | Type IA |
| d | Addition or replacement of a site responsible for the manufacture or testing of an excipient, when required to be described in the dossier | Type IB |
US FDA US Food and Drug Administration
21 CFR 314.70 and FDA guidance — 21 CFR 314.70(b)(1), (b)(2)(iv), (d)(1) · 2004 Guidance §V, §VII.C.1.b, §VII.B.3 (by analogy)
| Change | Category | Reference |
|---|---|---|
| Established non-compendial excipient: minor synthesis/recovery change, specification, impurity profile and physicochemical properties unchanged | Annual report | 21 CFR 314.70(d)(1) |
| Novel excipient: process or process-parameter change with no effect on specification (drug-substance analogy) | CBE-30 supplement | 2004 §VII.C.1.b |
| Change that may alter the excipient's impurity profile or physicochemical properties, or its specification | Prior approval supplement | 21 CFR 314.70(b)(2)(iv) |
| Biological/natural-source excipient: change in virus or adventitious-agent removal/inactivation | Prior approval supplement | 2004 §VII.B.3 |
Note: The 2004 and 2014 guidances give no examples for excipient manufacturing changes (§V defers components to SUPAC). Under 314.70(a)(2) the applicant assesses the change and classifies it by its potential for adverse effect, using the drug-substance categories as a guide. Where the excipient is covered by a DMF, the holder amends the DMF and the applicant reports under these categories.
Other items in II.2 Finished product c) Control of excipients
- 31 · Change in the specification parameters and/or limits of an excipient
- 32 · Change in test procedure for an excipient
- 33 · Change in source of an excipient or reagent with TSE risk
- 34 · Change in supplier of an excipient or reagent without TSE risk
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.