Extractables + Leachables
Our work
When patients receive treatment involving any pharmaceutical product or medical device, they can be exposed to small amounts of chemical substances known as "extractables and leachables" (E&L). These compounds can migrate from contact with pharmaceutical container closure systems (CCS), processing equipment, packaging or delivery systems, and subsequently become part of the administered dose.
It is critical for all parties that such leaching does not occur at a level that presents a significant safety or quality issue. Our approach to extractables and leachables risk assessment plays a critical role in this quality control and monitoring.
The E+L process
Extractables and Leachables Screening
Often, a comprehensive extractables and leachables study can return hundreds of compounds, all of which could be of potential health risk to a patient. We have developed a “screening” process where we can prioritise those substances that are more likely to result in a health risk. Compounds present at very low levels, or without inherent toxic hazards, can, with appropriate justification, be excluded from further more detailed and expensive toxicological risk assessment.
Toxicological Risk Assessment
Typically, our health risk assessments are based on E&L study results. The exposure, including details on treatment, would be described to us prior to starting our evaluation. We combine the hazard evaluation of the individual chemicals with exposure information to assess whether any significant health risks exist. Worst-case assumptions are made to address uncertainties. In cases of inadequate data, we use additional strategies such as read-across or a threshold of toxicological concern (TTC) approach. Where substance-specific hazard data are inadequate, read-across or a TTC approach may be introduced. Our risk assessors apply the applicable guidance from ICH or ISO, as well as guidelines developed and published by the Product Quality Research Institute (PQRI) and other expert groups.
Media/Expertise
Our team has been at the forefront of the E&L sector for many years. Pete Watts, one of our Toxicology Directors, along with Principal Toxicologist Chris Waine, is a regular presenter at E&L conferences. Chris is also an expert member of the BSI and ISO committees developing the 10993 series of standards for the biological evaluation of medical devices, including extractables and leachables testing and toxicological risk assessment.
Learn more about how our evaluation of extractables and leachables data can support your product development and meet regulatory guidelines - see case studies below, and please get in touch with us if you'd like further information.
Some of our case studies in this area
NAMs for NGRAs
Blog articles
Traditionally, toxicological risk assessment has involved identifying a point of departure (PoD) such as a NOAEL or LOAEL in a study of small creatures, adjusting it to be relevant to humans (to derive, for example, a TI or DNEL), and then calculating the margin of safety to a measured or estimated external exposure. As part of this process, toxicologists have to account for the uncertainties that arise in moving from the species, route and duration of the laboratory animal study to the real human world.
FDA memoranda: genotoxicity and carcinogenicity assessments of ENDS
Blog articles
As discussed in a previous blog post, the U.S. Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has issued several “scientific policy memoranda” that provide some great insights into the Agency’s evaluation process. In June 2024, the FDA made two new memos available that relate to the genotoxicity and carcinogenicity assessment of chemical constituents of Electronic Nicotine Delivery Systems (ENDS).
FDA memoranda: shedding light on health risk assessment of ENDS in PMTA submissions
Blog articles
In 2016, the United States (US) Food and Drug Administration (FDA) ruled that Electronic Nicotine Delivery Systems (ENDS) were to be regulated just like more traditional tobacco products, meaning that ENDS (e-cigarettes and e-liquids) are subject to premarket review requirements, despite containing no tobacco. ENDS manufacturers must therefore submit a Premarket Tobacco Product Application (PMTA) to the FDA Center for Tobacco Products (CTP) in order to have any chance of legally marketing their products in the US.
