Toxicological evaluation: the bridge between extractables and leachables
by Paolo Pescio, Eurofins BioPharma Product Testing, PaoloPescio@eurofins.com
During the drug development process, it is important to evaluate the potential for various chemicals to migrate from container closure or manufacturing systems into pharmaceutical products.
Extractables are compounds that can be extracted from the container closure system when in the presence of a solvent while leachables are compounds migrating into the drug product formulation from the container closure as a result of direct contact with the formulation.
On the basis of extractable data, toxicological evaluation gives some advice on how to design a leachable study.
The main question arising from an extractable study is about the safety of the extracted compounds. Tolerable Intake (TI) and Threshold of Toxicological Concern (TTC) concepts can help in answering.
The TI is an estimate of the amount of a substance to which each individual may be exposed over a specified period without appreciable risk.
The TTC concept was developed to define an acceptable intake for any unstudied chemical that will not pose a risk of carcinogenicity or other toxic effects. TTC is a de facto Tolerable Intake. In a practical sense, for a chemical with little or no toxicological data, the TTC approach is used to identify a screening intake level.
When evaluating the data coming from an extractable study, both TTC and TI can be applied.
The first step during the determination of TI is the selection of NOAEL or LOAEL coming from toxicological studies. The next step is the assessment of factors to compensate for uncertainties inherent to extrapolation of in vivo data to a given human situation. Finally, the comparison between the actual release and the TI and/or TTC is an indication about likelihood for adverse systemic effects to occur.
In the event the safety of a compound is in question, Eurofins can perform TI and TCC evaluations in real-life situations through its global leachable/extractable study capabilities. To that, Eurofins has decades of experience in helping Industries by designing and performing leachable/extractable studies and toxicological evaluations as well.
For more information visit www.eurofins.com/biopharm
