EXTRACTABLES AND LEACHABLES TESTING OF POLYMER DEVICE COMPONENTS

The examination of extractables and leachables from2.1. Safety Thresholds
medical products and devices is growing in importance.The PQRI Leachables and Extractables Working
This has arisen from ISO 10993 Standard BiologicalGroup have recommended two safety evaluation
Evaluation of Medical Devices - Part 18 Chemicalthresholds which have been justified from a
Characterisation of Materials and also from varioustoxicological or safety perspective:
guidelines produced by the FDA1,2. These guidelines· A Safety Concern Threshold (SCT) of 1.5
are concerned with various drug delivery devices, suchµg per day, which is defined as the threshold
as meter dose inhalers (MDI) and dry powder inhalersbelow which an individual leachable would have a dose
(DPI), and cover a wide range of aspects includingso low as to present negligible safety concerns from
extractables and leachables from rubber and plasticcarcinogenic and non-carcinogenic toxic effects;
components in these devices.· A Qualification Threshold (QT) of 5 µg per
In recent years the PQRIa Leachables andday, which is defined as the threshold below which a
Extractables Working Group has submitted bestgiven leachable is not considered for safety
practice guidelines3 for Extractables and Leachablesqualification (toxicological assessments) unless the
Testing to the PQRI Drug Product Technicalleachable presents structure-activity relationship (SAR)
Committee and the U.S. Food and Drug Administration.concerns
These guidelines have made an important contributionThese thresholds represent absolute exposures,
to Extractables and Leachables Testing of Orallyexpressed as total daily intake per day. They need to
Inhaled and Nasal Drug Products (OINDP).be converted into relative amounts expressed as an
This paper discusses the importance of Extractablesamount of a particular leachable per drug product or
and Leachables testing to Medical and Drug Deliveryextractable per mass of component. This threshold is
Devices, firstly considering the testing of inhalation drugknown as the Analytical Evaluation Threshold (AET).
delivery devices (OINDP) and then medical devices.The AET is determined by consideration of the SCT
2. EXTRACTABLES AND LEACHABLES TESTINGand the specific drug product configuration (e.g. total
OF OINDPnumber of doses in the Drug Product, number of
The assessment of Extractables and Leachables indoses per day, mass of individual components).
OINDP, as recommended by the PQRI, has three mainFor an extractables from a device component the
parts:AET (µg/g) can be determined using Equation 1:
1. ExtractablesThe rest of this paper can be viewed from the Rapra
2. LeachablesLimited website by following the link from the home
3. Routine Extraction Testingpage.
Each of these stages is guided by various safetyThis article is free to republish provided the resource
thresholds.a Product Quality Research Instituteinformation remains intact.