Regulatory requirements
Pharmtech:
What are the current regulatory expectations (for example among FDA and EMA) for E&L testing and removal?
Christiaens (Toxikon Europe): Ten years ago, there was a general consensus that leachables were a subset of the list of extractables that could be detected
in a properly designed extractable study. FDA and EMA guidance documents issued based on this assumption placed much emphasis
on performing risk evaluations on extractable results. However, a better understanding on the interactions of drug products
and packaging materials has made it clear that leachables are not always a subset of extractables. As a result, regulators
are requesting more leachables data that better reflect the actual risk to the patient.
Feilden (Smithers Rapra): The basic premise for carrying out E&L testing from both FDA and EMA remains the same whether it is for the container–closure
system or manufacturing environment. However, expectations have increased over the years, but have recently accelerated for
biological formulations because of the possible interactions of leachables with these formulations.
Kesselring (EAG Life Sciences):
There are several areas in which regulatory expectations regarding E&Ls and general impurity assessments are changing.
Through initiatives such as the forthcoming USP General Chapters <232> & <233> involving elemental impurities, regulatory expectations of specificity, accuracy, and control
are being implemented. Also, initiatives such as the recently "published for comment" glass delamination document of USP <1660> and the increase in requests for routine extractables testing of incoming lots of container material demonstrate that
the concept of control and prevention is being driven by regulatory agencies.
Killian (EMD Millipore): Regulatory bodies put the onus on drug companies to demonstrate that E&Ls do not pose a risk to the patient. As a rule, agencies
like to see leachables as low as reasonably achievable. They also like to see that the drug companies have thought out their
approach to E&L.
One noticeable increase in E&L expectations comes with the expanded use of single-use components. In the past, there was little
interest in E&L from process equipment because most facilities used stainless steel. Now, as more stainless steel is replaced
with single-use equipment, regulatory bodies want more E&L data, including data from the same filters that were not a concern
in stainless steel systems.
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