SFDA item 33 · II. Quality changes · II.2 Finished product c) Control of excipients
Change in source of an excipient or reagent with TSE risk
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 33 — official PDF, p. 44 ↗
| Variant | Change | Type |
|---|---|---|
| a.1 | Change from TSE risk material to vegetable or synthetic origin: — For excipients or reagents used in the manufacture of biological active substance or a finished product containing a biological active substance | Type IB |
| a.2 | Change from TSE risk material to vegetable or synthetic origin: — For excipients or reagents not used in the manufacture of biological active substance or a finished product containing a biological active substance | Type IA |
| b | Change or introduction of a TSE risk material or replacement of a TSE risk material from a different TSE risk material, not covered by a TSE certificate of suitability | Type II |
Conditions to be fulfilled and documentation to be supplied: see the official guideline, item 33.
EU European Union
Commission Guidelines C/2025/5045 — EUR-Lex ↗
Q.II.c.3 · Change in source of an excipient or reagent with TSE risk, which is used in the manufacture of an active substance or in a finished product
| Variant | Change | Type |
|---|---|---|
| a | Change in the source of an excipient or reagent from a TSE risk material to a material of vegetable or synthetic origin | Type IA |
| b | Change in the source of an excipient or reagent which is unlikely to present any risk of TSE contamination | Type IA |
| c | Change in the source of a TSE risk material, or introduction of a TSE risk material, not covered by a European Pharmacopoeial TSE certificate of suitability | Type II |
US FDA US Food and Drug Administration
21 CFR 314.70 and FDA guidance — 21 CFR 314.70(b)(1), (d)(1) · 2014 AR Guidance App. B 1.4 (by analogy) · 2004 Guidance §VII.B.3
| Change | Category | Reference |
|---|---|---|
| Animal-derived excipient replaced by a vegetable/synthetic source of the same grade and specification (treated as a supplier change) | Annual report | 2014 App. B 1.4 |
| Introduction of a TSE-risk (ruminant/animal-derived) material, or a switch between TSE-risk sources | Prior approval supplement | 21 CFR 314.70(b)(1) |
| Natural-source product: change in virus/adventitious-agent inactivation for a reagent or excipient | Prior approval supplement | 2004 §VII.B.3 |
Note: FDA has no TSE certificate procedure and no guidance example of a TSE-source switch. Replacing an animal source with a same-grade, same-specification non-animal material has minimal potential for adverse effect (AR, 314.70(d)(1)). Introducing TSE-risk material has substantial potential for a safety effect (PAS, 314.70(b)(1)); confirm with the CDER review division (2004 §I). BLA biologics follow 21 CFR 601.12.
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
- 34 · Change in supplier of an excipient or reagent without TSE risk
- 35 · Change in synthesis or recovery of a non-pharmacopeial excipient (when described in the dossier) or a novel excipient
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.