To help clairfy expectation, please see a response from the MHRA:

RSI refers to the Reference Safety Information. This is a list of medical terms detailing the Serious Adverse Reactions (SARs) that are expected for the IMP which is to be used by investigators as a reference point when assessing a SAR to determine whether it is a SUSAR. It is not the entire IB or SmPC but rather a section within the document i.e. Section 4.8 Undesirable effects. IB or SmPC changes that do not alter the RSI and have no impact on Risk/Benefit do not need to be submitted to the MHRA as substantial amendments.

Sponsors should be aware that any change to the RSI is a change to the Risk/Benefit and requires that a substantial amendment be submitted to the MHRA and approved before it is implemented in the trial. If you are a non-commercial sponsor using a IB provided by a Pharmaceutical company and they issue an update which contains RSI changes then you have two options. The first is to submit a substantial amendment to the MHRA to update your IB and change your RSI. The second option is to conduct and fully document a risk assessment of the changes and if you feel that you can justify not using the new RSI to again document it and continue with the old IB.

If you are using the SmPC for your RSI then the assessment should be made against the version of the SmPC that was submitted with your initial application as this is your approved RSI. If a new version of the SmPC is released then you should conduct an assessment of the changes and make a documented decision as whether you need to update your RSI or continue with the old version of the SmPC. If you decide you do wish to change to the new version of the SmPC then you will be required to submit a substantial amendment to the MHRA.

We hope this helps clarify expectations as sponsor.
MHRA Super Moderator