Question 1

What type of variation is “Change(s) in the summary of product characteristics, labeling and patient information leaflet related to post authorization safety study (PASS), periodic safety update report, risk management plan or SFDA drug safety monitoring activities.” under the SFDA Guidelines for Variation Requirements?

Accepted Answer

SFDA Guidelines for Variation Requirements v6.3, item 56 (III. Safety, efficacy, pharmacovigilance changes): a.1) Implementation of change(s) requested by SFDA following the assessment of post authorization safety studies (PASS), periodic safety update reports, risk management plans, or SFDA drug safety monitoring activities. — Implementation of agreed wording change(s) for which no new additional data are submitted by the MAH — Type IB; a.2) Implementation of change(s) requested by SFDA following the assessment of post authorization safety studies (PASS), periodic safety update reports, risk management plans, or SFDA drug safety monitoring activities. — Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH — Type II; b) Change(s) proposed by the MAH with the submission of a periodic safety update report, risk management plan, or post-authorization safety study (PASS) — Type II.

Question 2

How is “Change(s) in the summary of product characteristics, labeling and patient information leaflet related to post authorization safety study (PASS), periodic safety update report, risk management plan or SFDA drug safety monitoring activities.” classified in the EU?

Accepted Answer

Commission Guidelines C/2025/5045: C.3 Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Article 45 or 46 of Regulation (EC) No 1901/2006, or the outcome of a PRAC signal recommendation, or to adapt to a joint recommendation of EU competent authorities (e.g. a Core SmPC, or following the assessment of an Urgent Safety Restriction etc.): a) Implementation of the agreed wording — Type IA(IN); b) Implementation of the agreed wording that requires additional minor assessment (e.g. translations are not yet agreed upon) — Type IB; c) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH — Type II C.4 Change(s) in the summary of product characteristics, labelling or package leaflet due to new quality, preclinical, clinical or pharmacovigilance data.: -) Change(s) in the summary of product characteristics, labelling or package leaflet due to new quality, preclinical, clinical or pharmacovigilance data. — Type II C.9 Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the risk management plan: a) Implementation of changes to reflect the outcome of previous assessment — Type IA(IN); b) Implementation of changes which require additional minor assessment (e.g. change to the due date of obligations and conditions of a marketing authorisation and required pharmacovigilance activities in the risk management plan, including changes to the due date of study milestones, and template updates) — Type IB; c) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the holder where significant assessment by the competent authority is required — Type II

Question 3

How is “Change(s) in the summary of product characteristics, labeling and patient information leaflet related to post authorization safety study (PASS), periodic safety update report, risk management plan or SFDA drug safety monitoring activities.” reported to the US FDA?

Accepted Answer

21 CFR 314.70 and FDA guidance: Implement safety wording that FDA asks for, with no new data from the holder — CBE-0 supplement (21 CFR 314.70(c)(6)(iii)(E)); Holder adds or strengthens a warning, precaution or adverse reaction based on postmarketing data — CBE-0 supplement (2004 §X.C.2; 21 CFR 314.70(c)(6)(iii)(A)); Other labeling changes based on postmarketing study results (e.g., revised clinical sections, weakening or removing safety text) — Prior approval supplement (2004 §X.B.1). Periodic safety reports (21 CFR 314.80) do not themselves change labeling; the change goes in a labeling supplement, and anything touching PLR Highlights is PAS (314.70(b)(2)(v)(C)). FDA can also require safety labeling changes under FDCA 505(o)(4); the holder must respond within 30 days.

Change(s) in the summary of product characteristics, labeling and patient information leaflet related to post authorization safety study (PASS), periodic safety update report, risk management plan or SFDA drug safety monitoring activities.

SFDA Saudi Food and Drug Authority

EU European Union

C.4 · Change(s) in the summary of product characteristics, labelling or package leaflet due to new quality, preclinical, clinical or pharmacovigilance data.

C.9 · Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the risk management plan

US FDA US Food and Drug Administration

Other items in III. Safety, efficacy, pharmacovigilance changes

Variant	Change	Type
a.1	Implementation of change(s) requested by SFDA following the assessment of post authorization safety studies (PASS), periodic safety update reports, risk management plans, or SFDA drug safety monitoring activities. — Implementation of agreed wording change(s) for which no new additional data are submitted by the MAH	Type IB
a.2	Implementation of change(s) requested by SFDA following the assessment of post authorization safety studies (PASS), periodic safety update reports, risk management plans, or SFDA drug safety monitoring activities. — Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH	Type II
b	Change(s) proposed by the MAH with the submission of a periodic safety update report, risk management plan, or post-authorization safety study (PASS)	Type II

Variant	Change	Type
a	Implementation of the agreed wording	Type IA(IN)
b	Implementation of the agreed wording that requires additional minor assessment (e.g. translations are not yet agreed upon)	Type IB
c	Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH	Type II

Variant	Change	Type
a	Implementation of changes to reflect the outcome of previous assessment	Type IA(IN)
b	Implementation of changes which require additional minor assessment (e.g. change to the due date of obligations and conditions of a marketing authorisation and required pharmacovigilance activities in the risk management plan, including changes to the due date of study milestones, and template updates)	Type IB
c	Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the holder where significant assessment by the competent authority is required	Type II

Change	Category	Reference
Implement safety wording that FDA asks for, with no new data from the holder	CBE-0 supplement	21 CFR 314.70(c)(6)(iii)(E)
Holder adds or strengthens a warning, precaution or adverse reaction based on postmarketing data	CBE-0 supplement	2004 §X.C.2; 21 CFR 314.70(c)(6)(iii)(A)
Other labeling changes based on postmarketing study results (e.g., revised clinical sections, weakening or removing safety text)	Prior approval supplement	2004 §X.B.1