| The examination of extractables and | | | | |
| leachables from medical products and devices | | | | 2.1. Safety Thresholds |
| is growing in importance. This has arisen | | | | |
| from ISO 10993 Standard Biological Evaluation | | | | The PQRI Leachables and Extractables Working |
| of Medical Devices - Part 18 Chemical | | | | Group have recommended two safety evaluation |
| Characterisation of Materials and also from | | | | thresholds which have been justified from a |
| various guidelines produced by the FDA1,2. | | | | toxicological or safety perspective: |
| These guidelines are concerned with various | | | | |
| drug delivery devices, such as meter dose | | | | · A Safety Concern Threshold (SCT) of 1.5 |
| inhalers (MDI) and dry powder inhalers (DPI), | | | | µg per day, which is defined as the |
| and cover a wide range of aspects including | | | | threshold below which an individual leachable |
| extractables and leachables from rubber and | | | | would have a dose so low as to present |
| plastic components in these devices. | | | | negligible safety concerns from carcinogenic |
| | | | and non-carcinogenic toxic effects; |
| In recent years the PQRIa Leachables and | | | | |
| Extractables Working Group has submitted best | | | | · A Qualification Threshold (QT) of 5 |
| practice guidelines3 for Extractables and | | | | µg per day, which is defined as the |
| Leachables Testing to the PQRI Drug Product | | | | threshold below which a given leachable is |
| Technical Committee and the U.S. Food and | | | | not considered for safety qualification |
| Drug Administration. These guidelines have | | | | (toxicological assessments) unless the |
| made an important contribution to | | | | leachable presents structure-activity |
| Extractables and Leachables Testing of Orally | | | | relationship (SAR) concerns |
| Inhaled and Nasal Drug Products (OINDP). | | | | |
| | | | These thresholds represent absolute |
| This paper discusses the importance of | | | | exposures, expressed as total daily intake |
| Extractables and Leachables testing to | | | | per day. They need to be converted into |
| Medical and Drug Delivery Devices, firstly | | | | relative amounts expressed as an amount of a |
| considering the testing of inhalation drug | | | | particular leachable per drug product or |
| delivery devices (OINDP) and then medical | | | | extractable per mass of component. This |
| devices. | | | | threshold is known as the Analytical |
| | | | Evaluation Threshold (AET). The AET is |
| 2. EXTRACTABLES AND LEACHABLES TESTING OF | | | | determined by consideration of the SCT and |
| OINDP | | | | the specific drug product configuration (e.g. |
| | | | total number of doses in the Drug Product, |
| The assessment of Extractables and Leachables | | | | number of doses per day, mass of individual |
| in OINDP, as recommended by the PQRI, has | | | | components). |
| three main parts: | | | | |
| | | | For an extractables from a device component |
| 1. Extractables | | | | the AET (µg/g) can be determined using |
| | | | Equation 1: |
| 2. Leachables | | | | |
| | | | The rest of this paper can be viewed from the |
| 3. Routine Extraction Testing | | | | Rapra Limited website by following the link |
| | | | from the home page. |
| Each of these stages is guided by various | | | | |
| safety thresholds.a Product Quality Research | | | | This article is free to republish provided |
| Institute | | | | the resource information remains intact. |