Permeation :Permeation is defined as ‘the process by which a chemical agent migrates through the protective glove at a molecular level.
For the purposes of assessing the permeation characteristics of a glove, those engaged in the risk assessment will inevitably seek data specifically on cytotoxic drugs. While the shortage of such information was recently reported as a cause of concern8, the situation now has improved. Indeed, the complexity has grown to the extent that glove manufacturers provide chemical permeation data often based on three different standards:
-ASTM D6978-05 ‘Standard Practice for Assessment of Resistance of Medical Gloves to Permeation by Chemotherapy Drugs’
-ASMT F739-99a ‘Standard Test Method for Resistance of Protective Clothing Materials to Permeation by Liquids, Gases Under Conditions of Continuous Contact’
-EN374-3:2003 ‘Protective gloves against chemicals and micro-organisms - Part 3: Determination of resistance to permeation by chemicals’.
While all three norms provide methodologies for chemical permeation, in Europe EN374-3 is often cited as the preferred method, presumably because it is a European standard. However, it will be noted that only ASTM D D6978-05 has been specifically developed for testing of gloves to permeation by cytotoxic agents. A comparison table detailing the key differences between these three standards is provided above.
ASTM D D6978-05 :Increasingly ASTM D6978-5 is being specified by those engaged in risk assessments. This may be because this methodology is more aligned with the needs of those preparing or administering cytostatics.
In this respect the test temperature of 35º C (+/- 2º C) is close to that of the human hand, while it should be noted that with increasing temperature permeation accelerates.In view of the hazardousness of some chemotherapy treatments, it is reassuring to note that this standard offers the highest level of sensitivity as defined by permeation rate - in fact, 100 times more sensitive than the European norm.
Finally, ASTM D6978-05 explicitly mentions that only the thinnest part of the glove which is likely to be exposed to chemical contact (e.g. the palm or cuff) is to be tested.
The difference between ASTM D6978-05 and EN374-3:2003 in terms of determining permeation rates is evident from the comparison on Carmustine and Thiotepa:
If a risk assessment had been based on EN374-3: 2003, then it could have given the glove wearers a higher level of confidence in the glove’s resistance to permeation to Carmustine and Thiotepa.As glove thickness and material type are not the only factors that govern permeation, it is suggested that when evaluating the permeation characteristics of a glove only the data for a specific formulation is considered.
Penetration:Penetration is described by the HSE as “the bulk flow of a chemical agent through closures, porous material, seams, pinholes and other imperfection in the protective glove”.
The issue of penetration has been highlighted as a particular concern for operators working in isolators. This is especially relevant for those isolators working under positive pressure, as there is potential for leakage of the drug through holes.
As the gloves that are being used for personal protection against cytostatics are likely to be registered as Complex Design according to the PPE Directive (89/686/EEC), part of the registration process would have entailed testing them against EN374-2: 20039.
For disposable gloves this will invariably mean that the gloves will have undergone a watertight test and the porosity of a glove is defined by various performance levels.
According to EN374-1:200310 a glove is considered to be micro-organism resistant if it achieves a minimal Acceptable Quality Level (AQL) of 1.5 or Level 2.
Local Safety Standards :
Apart from the HSE, there are a number of other organisations in Europe that have issued specific guidance on personal safety for the handling and preparation of cytotoxic drugs.
These include the following:
-Berufsgenossenschaft fuer Gesundheit und Wohlfahrt (BGW) - the professional association for the German health service and social services has produced a leaflet M620 ‘Safe handling of cytostatics’, which is frequently cited in the literature
-TRGS 525 - technical rules for working with dangerous material
-Suva (Schweizerische Unfallversicherungsanstalt) - check list PPE From. 6709/1
-Institute for Applied Healthcare Sciences (IFAHS) - Quality Standard for the Pharmacy Oncology Service in Germany
-Institut National de Recherche et de Sécurité (INRS) - les médicaments cytstatiques en milieu de soins; toxicité et risques professionnels. Fiche Médico-Technique 33; recommendations pour la prévention des risques professionnels. Fiche Médico-Technique 36
Product protection: Annex 1 to the EC Guide to GMP mentions that “the manufacture of sterile products is subject to special requirements in order to minimise risks of microbiological contamination, and of particulate and pyrogen contamination”.