Rushing (ABC Laboratories):
Regulatory expectations continue to increase. Drug–device combinations that historically garnered little regulatory attention
in regards to E&L are now receiving more in-depth scrutiny. Over the past couple of years, several oral and dermal solution
formulations have received either deficiency letters or specific information requests from FDA asking for in-depth E&L information
for drug products. It is likely that this trend will soon spread to affect products that were traditionally considered to
be at a lower risk of E&Ls as emphasis in this area continues.
How do regulatory expectations for E&L testing and toxicological assessments vary between EMA and FDA?
Christiaens (Toxikon Europe):
The regulatory expectations in Europe (EMA) and the US (FDA) are very similar. However, in my experience, variability
between different reviewers within the same authority regarding what level of documentation they expect is higher than the
difference in official standpoints concerning what documentation to submit with regard to the qualification of the pharmaceutical
packaging materials between FDA and EMA.
Feilden (Smithers Rapra): The significant differences between the two regulatory authorities are in the amount of information supplied on how to conduct
testing. FDA points to the Product Quality Research Institute (PQRI) recommendations, but the EMA guidance is a lot shorter
and doesn't go into specifics. Generally, PQRI recommendations tend to be followed because they are more stringent than EMA.
PQRI has a level of 0.15 µg/day for identifying species whereas the EMA has 1.5 µg/day. There doesn't appear to be any difference
between toxicological assessments for either regulators, but a toxicologist would be able to confirm this.
Kesselring (EAG Life Sciences): Although it is difficult to predict how developing regulatory requirements may contrast, I have found the current expectations
for E&L testing between EMA and FDA to be more similar than different. I believe the background that has allowed this to occur
is that the development of industry E&L study concepts has coincided closely with the development of the International Conference
on Harmonization. It is also notable that the E&L industry driving force of the PQRI has been a multinational effort both
in its recommendation development, as well as its promotion of the developed concepts.
Killian (EMD Millipore): There are some differences between EMA and FDA. EMA is quicker to incorporate ICH documents and is more willing to put out
guidance documents (e.g., the 2009 CHMP Guideline on the Limits of Genotoxic Impurities). FDA is more noncommittal, leaving
it up to the drug company to demonstrate that E&Ls do not pose a risk to the patient.