When we are unfortunate enough to have to take a drug or to be in contact with some sort of medical device, we are going to be exposed to more than maybe we bargained for. Small amounts of “leachable” chemicals will have probably migrated from that drug’s contact with processing equipment, packaging or delivery systems and that device’s contact with our bodily fluids. In this health precautionary age, the identification, quantitation and toxicological assessment of these unwelcome migrants is essential.

So, what do we mean when we talk about Extractables & Leachables (E&Ls)?

Extractables are those chemicals that are liberated from a drug or device when in contact with an appropriate solvent under exaggerated time and temperature conditions to illustrate the worst-case. Leachables on the other hand are the likely migrating entities under clinically relevant or typical use.

How do we test for them?

When testing for E&Ls, chromatography (in its numerous forms) has become standard industry practice to screen for organic compounds.

Common detection methods & techniques:

  • Volatile Organic Compounds (VOCs): Gas Chromatography and Mass Spectrometry (GC-MS) combined with Headspace sampling
  • Semi-Volatile Organic Compounds (SVOCs) and liquids: “direct” injection gas chromatography
  • Non-volatile Organic Compounds: Liquid Chromatography – Mass Spectrometry (LC-MS)
  • Inorganic Extractables (including metals): Inductively Coupled Plasma – Mass Spectrometry (ICP-MS)

The resulting E&L profiles identify and attempt to chemically characterise every compound present in an extract above a defined and toxicologically justified evaluation or reporting threshold - the Analytical Evaluation Threshold (AET).

What bibra can do to help?

Bibra's core competence in toxicological hazard and risk assessment can be bought fruitfully to bear at all stages of the sometimes tortuous E&L journey. This is most obvious in the assessment of the leachables (and high-priority extractables) where the objective is defensible Tolerable Intake (TI) and Margin of Safety (MoS) values. We also have a value earlier in the game, most usefully with those monstrous extractables reports that have identified far too many compounds, most of which are clearly not going to pose any health risk to patients. To exclude most of these from further, more detailed, and expensive toxicological risk assessment, we have developed a “extractables and leachables screening” process to prioritise substances that are more worthy of this detailed scrutiny. Whilst we profess no similar expertise in analytical chemistry we contend we can also sometimes bring value to the initial project discussions over the planning of the E&L programme itself. Extraction solvents and conditions, for example, can be tailored to suit the product based on its composition and anticipated contact with the patient. In cases where a health risk cannot be ruled out based on the toxicological assessment of an extractables profile and traditional leachables studies are not practical, “simulated leachables” studies can be designed to more closely mimic the typical use of the product, and health risks can therefore be refined using these more relevant data.

To learn more about how bibra can support you with professional advice or further guidance on E&Ls screening, contact us today.

Contact us