Risk Assessment Strategies in Extractables and Leachables

Risks assessments are a key element in extractables and leachables testing. There are many factors involved in ascertaining the specific risks and how this ultimately impacts the biocompatibility of a medical device.

There is a range of scientific, quality control, and regulatory approaches that are employed to regulate and judge the risks of substances that are unknowingly added to products that enter the human body, known as extractables and leachables.

What are Extractables and Leachables

Extractables are substances that extract from a medical device or from pharmaceutical packaging under laboratory conditions. Leachables are chemicals that extract from medical devices and are transferred to the patient or those chemicals from pharmaceutical packaging which extract into the drug product and thus enter the patient.

There are three main problems which can result from introducing extractables and leachables into a pharmaceutical or medical device product. One of these issues is that the leachable may be toxic and could pose an adverse health risk to the consumer. The second is that the leachables may interact with the formulation of the drug product or medical devices properties, which could impact its stability and potency. Finally, the leachables may interfere with an assay that is critical to measuring and understanding a crucial property of the drug product or device. This is why risk assessments must be carried out on products to determine the presence of extractables and leachables.

Risk Assessment Elements to Consider

Dosage

The dosage of a product containing extractables and leachables has a substantial effect on the risk. Larger, more frequent doses create a greater risk of exposure to leachables.

Toxicity Classification

The toxicity of leachables and the equivalent limits are largely dependent on the identification of the leachables. There are some extractables and leachables which are so toxic that the limits are set to be as low as reasonably practicable. For many other extractables and leachables with lower toxicity, a threshold approach can be utilized based on the ICH M7 guidance.

Administration Route

Product categories that have the most significant concern regarding the route of administration are those pertaining to aerosols, sprays, and injectable solutions. For medical devices, it is generally those which are permanent implants.

Material of Construction

Generally speaking, metals and glass have a low risk of harmful extractables and leachables. Plastics and elastomers are higher-risk materials as the more crystalline the materials are, the less likely it is that extractables and leachables will leach from the material.

Extractables and leachables in cured elastomers are far more likely to have direct health risks than those in thermoplastics. To mitigate this risk, contact area and time should be minimized.

The Bottom Line

The goal of all risk assessments should be the safety of the end-users of the drug product or device. The highest risk areas receive the highest scrutiny and to access the risks of extractables and leachables many factors must be considered.

If you would like assistance in your risk assessment strategy or general extractables and leachables testing queries, RQM+ Lab Service has a wealth of knowledge to assist you.

Get in touch with the RQM+ Lab Service team today.