Technical and regulatory feasibility of a new sterile preparation posing health and environmental risk: the case of 30% ethanol eye drops

Objective
In refractive surgery, 30% ethanol diluted extemporaneously from 96% ethanol is used for ocular instillation, exposing patients to risks of error, contamination or even confusion with other indications of 96% ethanol. To ensure medication management safety, this study aimed to evaluate the technical and regulatory feasibility of preparing this formulation within a hospital pharmacy, considering the sterility requirement of ophthalmic preparations and the safe handling of concentrated ethanol.

Methods
After assessing the regulatory validity of the preparation, its technical feasibility was evaluated. A process map was conducted. Risk mapping based on predefined generic hazards highlighted hazardous situations which were then subjected to a prospective risk assessment including a description of the causes and consequences followed by an initial criticality scoring. This rating was achieved by multiplying three scores each established on a 1-to-5 scale: likelihood of occurrence, severity of consequence and level of existing control measures. A risk mitigation plan was implemented to reduce residual risk to an acceptable level. For ethanol-related hazards, toxicity and flammability risks were assessed through calculations of evaporation rate, concentration and volumetric percentage in the working atmosphere. Estimated values were compared to occupational exposure limits and the lower flammability limit.

Results
The preparation met regulatory criteria, provided it remained compounded as a magistral preparation with a documented medical indication and in the absence of an appropriate commercial dosage form. Technically, the production area was equipped with a cleanroom supplied with filtered air, a class II biological safety cabinet and qualified personnel. The process map identified 7 main steps and 29 sub-steps. Fifty-four risk situations were identified, of which 42 were analyzed (others having overlapping causes or hazards). Fourteen situations were deemed unacceptable, leading to a corrective action plan consisting of 14 actions, including 8 priorities, such as drafting a preparation file, the supply of sterile primary packaging materials and the microbiological validation of equipment cleaning. Under the defined working conditions, ethanol use posed no significant risk to personnel or the environment.

Discussion & conclusion
This approach enabled the implementation of a new magistral sterile preparation with controlled risk. It could be further enhanced by a self-assessment of good practices compliance and direct atmospheric monitoring of ethanol concentrations in the working area.

See the poster