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

A visual representation of how bibra approaches the E&L risk assessment 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.


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

ISO 18562 evaluation of a medical device in contact with the breathing gas pathway

Case study

As part of a large programme of work in evaluating the safety of a new endotracheal tube device, bibra was asked to evaluate the health risks posed by exposure to potentially hazardous substances that may be transferred to the patient via the gas stream during device use.

PDE for a leachable in an intravenous pharmaceutical

Case study

ICH defines a Permitted Daily Exposure (PDE) as a pharmaceutically acceptable intake “protective of public health for all patient populations” and provides specific guidance on the derivation of PDEs for threshold toxins identified as residual solvents (Q3C guideline) and elemental impurities (Q3D guideline) in pharmaceuticals.

Derivation of an intravenous PDE for a common leachable

Case study

Chemicals that leach into drug products from processing or manufacturing equipment, drug delivery systems and/or packaging may pose a health risk to patients.

Biocompatibility review under ISO 18562 guidelines

Case study

The client commissioned bibra to review a biocompatibility report following feedback from US FDA.

Evaluating the health risks posed by extractables and leachables from an ENDS device

Case study

In order to market their latest product in the United States, the client was intending to submit a Premarket Tobacco Product Application (PMTA) for a pod-based ENDS device.

Toxicological risk assessment of leachables from a syringe medical device

Case study

The company had commissioned leachables studies on a syringe medical device intended for flushing of intravenous catheters/tubing with saline. The leachables profile was examined at two time points (day 0 and about 2 months) and numerous substances were detected at low concentrations.

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