Safety concerns (Important identified risks, important potential risks and missing information) in PBRER/PSUR and RMPs

Safety concerns (risks- important identified risks, important potential risks and missing information) can be considered the most scrutinized and most important part of any safety document such as PSUR/PBRER or RMP.

  • Usually we only want to specify something as missing information if we want to study exposure in those patient groups further.
  • Subgroups of the targeted populations that are expected to frequently use the product and are not included in the clinical development program can be considered as missing information, e.g. patients with impaired renal and hepatic function, children, elderly, pregnant and lactating women, off-label use.
  • Exclusion criteria should not automatically translate into missing information.
  • The assessor should rather consider clinical relevance and likely real-world use to be of importance for the missing information.
  • If the indication implies chronic use, long-term use should be considered as missing information if not studied.
  • If studies of relevant drug-drug interaction have not been done, this should be considered as possible missing information.
  • If none of the above is available or CCDS is recently updated and RMP is not as per current safety information, medical reviewer may need to propose safety concerns.
  • Safety sections of the RSI provide the basis for safety concerns in such situations.
  • Check CMDH for the same molecule
  • If safety concerns are available and CMDH is updated recently (let’s say 1–2 years) we can consider the same
  • If not, consider other regulatory website such as EPAR
  • Previous report containing safety concerns such as PSUR or latest RMP
  • If nothing of the above is available, company medical reviewer can provide safety concerns based on applicable RSI, SmPC or CCDS
  • Inclusion of any event in section 4.8 Undesirable events of the RSI/SmPC is the highest degree of PVG by all means!
  • Deriving and providing safety concerns for PSUR/ PBRER or RMP is a scientifically vigorous task and needless to say, highly scrutinized by all stakeholders including QPPV, client and regulators. I hope you liked the article!! Please leave your feedback in the comments and have a great day!
  • Look forward to discussion :-)



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🏳️‍🌈 Aditi Sheth 🏳️‍🌈

🏳️‍🌈📚 Bookworm fueled by curiosity | 750+ Certificates | PBRER | Aggregate reports | Artificial Intelligence | Trained Psychologist | Introvert | ISFJ |MBBS