Frequently Asked Questions
4. What is the difference between an extractables and leachables risk assessment and an extractables and leachables safety assessment?
An E&L risk assessment looks at the various unit operations associated with the manufacture of a pharmaceutical, ENDS or e-liquid product, and identifies failure modes associated with leaching of components from the materials involved in each of these unit operations. Using failure mode and effect analysis (FMEA), probability & severity factors are assessed for each failure mode. As a result of the FMEA assessment, each failure mode is defined as being either high, medium or low risk.
As such, the outputs from the risk assessment process drive mitigation activities towards the high and medium risk failure modes (i.e. time, resource and budget is directed at those areas of the manufacturing process most at risk of generating leachables), whilst providing a scientifically robust justification for discharging any risk associated with the low risk failure modes.
An E&L safety assessment is performed on any extractable or leachable that is observed at levels above a predefined threshold from a corresponding extractables or leachables study. The levels observed are reported to a toxicologist, who will then carry out a paper based exercise to determine whether the reported level is likely to present a risk to the health of patients/consumers.
The toxicologist uses a variety of methods to determine whether the reported level of the extractable/leachable observed is acceptable or not, including
a literature search for published data on the extractable/leachable in question
in silico modelling to predict toxicity based on the structure of the extractable/leachable in question (e.g. Toxtree; QSAR; Leadscope; DEREK, etc)
Based on the results of their investigations, the toxicologist is able to provide a scientific justification for whether the extractable or leachable in question is safe at the level reported.
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