Archives: FAQs

What is a Suspected Unexpected Serious Adverse Reaction (SUSAR)

An adverse event requires the evaluation of the presence of the following criteria by the sponsor:

  • Is it a serious event?
  • Is there reason to suspect a causal relationship with the administration of the investigational medicinal product?
  • Is the adverse reaction, by its nature and severity, inconsistent with the reference information for the investigational medicinal product?

If the investigator or the sponsor judges all these criteria to be fulfilled, this constitutes a case of a suspected unexpected serious adverse reaction (SUSAR).

What are the six seriousness criteria for a Serious Adverse Reaction?

  • Death
  • Life-threatening
  • requires inpatient hospitalization or prolongation of existing hospitalization
  • Disability or Permanent Damage
  • Congenital Anomaly/Birth Defect
  • Important Medical Event (IME): when the event does not fit the other outcomes, but the event may jeopardize the patient and may require medical or surgical intervention (treatment) to prevent one of the other outcomes

What is an Unexpected Adverse Drug Reaction?

An adverse reaction, the nature or severity of which is not consistent with the applicable product information.

What is Adverse Drug Reaction (ADR)?

A response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function.

What is an Adverse Event?

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

What is Pharmacovigilance (PV) or Drug Safety?

Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem. (WHO 2002)

Could Occupational Exposure Limits (OELs) or Occupational Exposure Bands (OEBs) be used to support assessment of products to determine whether they may be highly hazardous?

Yes. Extrapolation of an OEL or OEB (lower end of the range) to a preliminary Permitted Daily Exposure (PDE) can be simply done by using the following formula: PDE (µg/day) = OEL (µg/m3) x 10 m3 (the volume air breathed by a worker in 8 hours). Additional adjustment factors may be needed due to potential differences in target population (worker vs patient), route of exposure etc. If the resulting PDE value is 10 µg/day or lower the product should be considered as highly hazardous.

Is the application of the Threshold of Toxicological Concern (TTC) as applied in the guideline of mutagenic products of 1.5 µg/person/day concept an acceptable default approach to establish an HBEL?

Yes, except in the case of highly sensitising active substances and products.

Where products for paediatric populations are manufactured in shared facilities with products intended for administration to adults or to animals, do the HBELs need adjustment?

In such facilities the standard body weight value for adults of 50 kg used for calculating the HBEL should be replaced by a lower body weight value (e.g., children: 10 kg, new-borns: 3.5 kg, prematurely born new-borns: 0.5 kg) and used for HBEL determination for all relevant products in order to reflect the worst case situation.

How can inspectors determine the competency of the Toxicology expert developing the health-based exposure limit?

Inspectors should evaluate the company’s assessment of the competence of their expert in the field by reviewing justification of experience and qualification.