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Insights from Certara’s Experts: Navigating DSURs, EUCTR, FDA Guidance, and the Future of AI

Looking for clarity on global safety reporting?

In this Ask the Experts session, Mary Pilkington answers the five biggest questions safety professionals are asking today. From regional DSUR requirements to AI’s evolving role, this video gives you practical, actionable insights to stay compliant and work smarter.

 

What You’ll Learn

How do you master regional DSUR appendix requirements?

  • Understand why appendices are critical for global compliance.
  • Know which R1–R10 appendices are required across the UK, EU, US, China, Canada, and New Zealand.

How should you adapt DSURs to the EU Clinical Trials Regulation (EUCTR)?

  • Apply new EU-specific appendices and GDPR-driven subject ID rules.
  • Align annual RSI updates with DSUR data lock points.

How can you reconcile FDA and ICH DSUR guidance?

  • Recognize that the FDA is shifting toward DSUR-only submissions, replacing IND annual reports.
  • Adjust to differences in waiver requirements and reporting details for global compliance.

How do you create synergy across regulatory documents?

  • Reuse common sections, tables, and analyses across DSURs, RMPs, and PBRERs.
  • Harmonize reporting cycles to improve consistency and save time.

What role will AI play in aggregate safety reporting?

  • Current adoption is limited due to technical challenges with complex files.
  • Emerging tools will soon streamline authoring and automate parts of the process.

 

Why Watch: Three Reasons to Tune In

  1. Stay compliant with the latest global regulatory changes.
  2. Save time by streamlining safety document workflows.
  3. Prepare for the future with insights on AI in regulatory writing.

Clear, practical answers to today’s top 5 safety reporting questions—straight from an expert.

View transcript

So hello and welcome to this month’s episode of Ask the Experts which is dedicated to aggregate reports.

My name is Mary Poveington and I’m the service line head for safety and PV here at Sutalla.

So the first question I received was, what are the regional appendix requirements for D issuers? At last count, there are about ten regional specific appendices for D issuers depending on how your template has been set up. So I’ll break them down for you by region and country. So appendix R1, which is the cumulative summary tabulation of serious adverse reactions, is applicable for the UK, EU and China.

Appendix R2, which is the list of subjects who died during the reporting period and appendix r three which is the list of subjects who dropped out of clinical trials in association with an adverse event during the reporting period are applicable to the US, EU and China.

Appendix r four which is significant phase one protocol modifications.

Appendix r five which is significant manufacturing changes also known as the CNC appendix.

Appendix r six which is the description of general of the general investigational plan for the coming year and appendix r seven which is a log of outstanding business with respect to the US IND as it would suggest or applicable only for the US.

Appendix r eight is the signal log or summary of all new ongoing and closed signals for the reporting period which includes a summary description of the processes used to review worldwide safety data is applicable to the UK EU, and Canada, and potentially New Zealand. Appendix r nine, which is which are the summary tables of changes in the clinical trial protocol or new clinical findings, and both nonclinical and pharmaceutical changes or new findings occurring during the reporting period as well as appendix r ten which is the description of the general investigational plan for clinical trials, long clinical studies, and pharmaceutical studies for the next reporting period are applicable for China only.

And I just wanted to add a note here as well that, the appendices for China can sometimes be provided as an annex, which is separate to the other regional appendices.

So the next question was, how does the EU CTR regulation affect D issuer content? So the CTR regulation affects D issuer content in several ways.

Firstly it highly recommends updating the RSI section of the IB once a year in alignment with the DSUR data lock point.

If this process is followed the RSI in effect at the end of the reporting period will include all safety information as of the data cut at the start of the reporting period.

Second, additional EU specific regional appendices were added in alignment with other countries or regions and I refer you to my previous response.

Third to comply with gdpr subject identifiers should not be included in data listings such as the inter falsial listing or the listings of deaths and dropouts due to AEs. Finally, the cumulative summary tabulations of AEs should include the absolute number of patients that have been treated.

So the next question was, how is the proposed FDA de issuer guidance different from ICH guidance? So, as you know, since twenty eleven, the FDA has accepted de issuer in lieu of IND annual reports.

However, in a recent proposal from the FDA, they have suggested moving forward with just d issuers, albeit with some differences to the d issuer format which is accepted in other ICH regions.

Now the differences between the ICH d issuer and the fda d issuer are minor and straightforward if the DHR is only being submitted to the US.

However, for DHRs being submitted globally care needs to be taken to ensure that all US specific elements are included.

And these are firstly obtaining a waiver from the FDA to use the development international birth date or the DRBD rather than the IND approval date to drive the reporting schedule.

Secondly, in section one of the d s u r, you need to state that the use of mode of action is synonymous with mechanism of action.

In section three, they have added two new requirements to report on regarding actions taken for safety reasons.

In appendix five the FDA would want you to include the NCT number, the date of first subject consent, and any patient demography by study, which is slightly different to the requirement that you have for appendix four.

And finally, in the star line listing, the FDA want you to include the ind safety report reference number.

So as I said, thirty minor changes, but this guidance is still in draft, and so this may change, once it’s finalized.

So the next question I had was what are the synergies between d s u r’s, r m p’s, and p b r e r’s or p v r’s?

So these documents, as you know, are modular, and they’ve been designed as such to facilitate the use of similar or even identical information in all three documents.

However, it is important to ensure that the interval data and the DSUR and PSUR or PD RER align. For example, interval data in an annual DHR may not be appropriate for the P for the PBRER for the six month, two year or three year cycle and vice versa. Of course, if you want to dive deeper into the harmonization of sections of the DHR PBRER, and RMP, please download our white paper, which is entitled DHRs, RMPs, and PHRs, the harmonization of pharmacovigilance documents.

So the final question I received was, can I, can AI be used to support authoring of aggregate safety reports yet?

And the short answer is not quite yet. So many companies from big pharma to small biotechs to CROs are working on implementing their own AI to enhance regulatory writing.

But the focus has really been on clinical and submission documents, but unlike CSR CSRs that have a small number of source documents, for example, your t f l’s, your sap and protocol, all in work format, aggregate reports can have hundreds of source documents in multiple different file formats from, for example, excel, word, pdf, and you can get some information in email.

So currently, AI still struggles with large Excel spreadsheets and PDF seance forms, but it’s improving all the time. So it won’t be long until this is cracked and and we’ll need to be ready. So that just needs me then to, thank you all for joining this episode of ask the experts.

Don’t forget to subscribe to our channel and follow Sotara on LinkedIn, Just to make sure you never miss an update. And thanks again for watching and I’ll see you next time.

Speakers:

Associate Director, Service Line Head, Certara

Mary Pilkington, PhD, has over 20 years of experience in regulatory writing. She is an expert in writing pharmacovigilance documents, including development safety update reports, periodic benefit-risk evaluation reports, periodic adverse drug experience reports, and risk management plans. She is process-driven, having created standard operating procedures and working instructions for pharmacovigilance documents, and is client-oriented, developing long-term governance relationships. She also has proven skills in training and developing junior writers to become pharmacovigilance document subject matter experts. She is an associate director and the service line head for safety/PV at Certara.

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Related Resources

  • DSURs, RMPs, and PSURs: The Harmonization of Pharmacovigilance Documents — Read the white paper
  • Clinical Trials Regulation (EU) No 536/2014: The Impact on Annual Safety Reporting — Read the blog