Dear Madam, Sir,

CytoPrevent, a group of scientific experts, would like to use the opportunity to give our comments and suggestions on “work involving exposure to cytostatic agents”.
We appreciate the appraisal as a step forward to improve worker’s safety and health because recent studies of INRS have shown that healthcare workers are daily exposed to these hazardous drugs.
We understand the focus on carcinogens and mutagens under the CMD and CLP regulation but we like to stress that there are many cytostatic agents expressing reprotoxic effects which cannot be denied. It would have been more practical to implement these in the current appraisal to give an overview picture of all the cytostatic drugs under concern and to offer more clarity to (healthcare) workers handling these toxic drugs every day.

For example, methotrexate and 5-fluorouracil are not listed but both drugs are considered as reprotoxic and belong to the cytostatic agents most frequently prepared and administered.

Regarding the analysis of the scientific literature, we miss two important studies that should be included:
1) Ratner P.A. et al. (2010) Cancer incidence and adverse pregnancy outcome in registered nurses potentially exposed to antineoplastic agents. BMC Nursing, 9(1), 15.
2) Dranitsaris G. et al. (2005) Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature.
J Oncol Pharm Pract, 11(2) 69-78.

Although immunotherapy was retained because of acting with another mechanism some recent publications have indicated concern about the potential health risk of these drugs. In addition, some carcinogenic/mutagenic drugs including the immunosuppressant ciclosporin and antivirals such as ganciclovir sodium and zidovudine are missing. The same for bleomycin, capecitabine, carboplatin, rizotinib, 5-fluorouracil, mitoxantrone hydrochloride and topotecan possessing mutagenic properties. In conclusion, the focus should be much broader than cytostatic drugs as only antineoplastic drugs as a part of the total group of hazardous drugs is evaluated in the current appraisal.

We support the need of raising awareness, training of staff, and development of guidelines and standards of practice but all proposed measures have to be enforceable and not voluntary.
The adoption of mandatory standards is the only way to ensure compliance and provide safety for healthcare workers. Guidance is to guide and in general not obliged.

We would recommend surface wipe sampling in addition to biomonitoring to evaluat environmental contamination, and to validate procedures and cleaning. Although biomonitoring measures exposure, implementation of testing and interpretation of the results CytoPrevent for ANSES – December 2020 2 is rather complex. Surface wipe sampling could serve as a good alternative, as a first step to validate working routines, identify areas for improvement, and provide a means to objectively measure those improvements.

In the CMD is indicated that if replacement of the carcinogen or mutagen is not possible, a closed system or other measures aiming the reduction of worker’s exposure to a level as low as possible, has to be implemented. For pharmacy technicians and especially nurses involved in the preparation and administration of cytostatic drugs it is not clear what is meant with a closed system. It is very vague and should be described more precisely.
Does it mean that a Closed System drug Transfer Device (CSTD) has to be used? If so, it should be clearly stated and described. If not, what is meant then? A clear definition has to be added to the appraisal to clarify what is meant.

We appreciate to receive your views on our comments and suggestions.
With kind regards.

On behalf of CytoPrevent
Dr. Paul Sessink PhD
Chairman