Extractables and Leachables (E&L) Hazard and Risk Assessments

Bibra provides valuable support to the pharmaceutical, medical device and process equipment industries by producing risk assessment reports relating to extractables and leachables (E&L).

extract&leachDuring manufacture and use, pharmaceutical products are in contact with processing equipment (reaction vessels, tubes, filters, chromatography columns, etc), packaging (glass vials, plastic bags, etc) and delivery device components (needles, catheters, syringes, caps, seals, stoppers etc). Small amounts of chemicals may leach from any or all of these into the pharmaceutical, and subsequently be delivered to the patient along with the dose. It is critical for all parties that such leaching does not occur in quantities that significantly alter the safety, identity, strength or quality of the drug. Extractables and leachables studies play a critical role in quality control and monitoring.

E&L studies are carried out sequentially. First, the contact materials are extracted by various established solvents under exaggerated incubation conditions of time and/or temperature. A range of analytical techniques (e.g. GC-MS, LC-MS, ICP-OES and FTIR) are used to identify extractables (sometimes only tentatively or generically); semi-quantification is often possible at this stage. The risk assessor can use the extractables study to identify those that are critical for confirmation and better quantification in a leachables study.

A leachables analysis is then carried out, identifying and quantifying the chemicals that actually migrate into a drug product under normal conditions of production, storage and use. This may be preceded by accelerated leaching and/or stability studies using the pharmaceutical formulation; these are very useful in the risk assessment process.

Typically, a bibra risk assessment is based on the leachables study results. The client describes the exposure, including treatment dose, dosing route, dosing frequency, and its likely duration. Bibra combines the hazard assessment of the individual chemicals with exposure information to assess whether any significant health risks exist. Worst-case assumptions are made to address uncertainties. Where substance-specific hazard data are inadequate, read-across or a TTC approach may be introduced.

The end product is an independent, expert risk assessment report explaining transparently whether the patients are at any significant health risks or not as a result of leaching substances. This reassures clients or provides the information needed to modify processes, and helps to ensure that patient health is not compromised by the inevitable low level migration from packaging and processing contact materials.

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