Q. During leachable testing pharmaceutical companies often deals with targeted leachables and unknown leachables. In order to propose acceptance criteria's for targeted leachables you can come across leachables where no toxicological information exists. How do you as a toxicologist then propose acceptance criteria for such a targeted leachable?
My favoured approach is to use the Threshold of Toxicological Concern.
Q. During toxicological evaluations an important factor is the dosage regime of the drug product. What is your recommendation with respect to dose regime - to use clinical maximum doses, maximum doses according to product recommendation and packaging leaflet or other dosing?
Preferably, the maximum recommended daily dose in the packaging leaflet. Otherwise try to rationalise a dose to cover 95% of the actual clinical use.
Q. As a toxicologist involved in the ICH M7 genotoxic compounds guideline process, what are your thoughts on the on the proposed Safety Concern Threshold (SCT) from the PQRI tox group for Parenterals and Opthalmics (PODP's) being identical to the Threshold of Toxicological Concern (TTC) for genotoxic compounds?
I completely agree. From a patient's perspective the source of impurities should not matter.
Q. Furthermore what are your thoughts on the differentiation of the PQRI tox group for Oral Inhaled Nasal and Pulmonary Drug Products (OINDP's) compared to the TTC level?
The rationale for the difference between OINDP and PODP is well explained in the publication by Paskiet et. al. http://journal.pda.org/content/67/5/430
Q. Working as a toxicologist and performing E&L toxicological evaluations within in the area of packaging, devices and SUS what is your experience and thoughts for the risk of having critical leachables in packaging, devices and SUS systems?
Generally, the levels of observed leachables from materials, we use, are very low, therefore (usually) the potential risk for an adverse effect for the patient is also very low. Some PODPs may have a high daily dose level and therefore theoretical exposure may also be higher and more challenging to justify.
Q. Many pharmaceutical companies perform risk based evaluations as a screening tool to choose which SUS systems to document with respect to extractables and leachables. As a toxicologist what are your thoughts for the most critical parameters in the risk evaluation of SUS systems?
The most critical parameters are the sizes of batches versus surface area and material type and quality grade
Q. What are you most looking forward to about joining the E&L conference again this year?
I look forward to discussing some multi-disciplinary challenges in setting acceptance criteria for leachable substances. I also look forward to receiving an update on the PQRI recommendations and networking with all the attendees.