Pharmaceutical Oral Formulation of Methionine as a Pediatric Treatment in Inherited Metabolic Disease.

L-Methionine (Met) is an essential alpha-amino acid playing a key role in several metabolic pathways. Rare inherited metabolic diseases such as mutations affecting the MARS1 gene encoding methionine tRNA synthetase (MetRS) can cause severe lung and liver disease before the age of two years. Oral Met therapy has been shown to restore MetRS activity and improve clinical health in children. As a sulfur-containing compound, Met has a strongly unpleasant odor and taste. The objective of this study was to develop an optimized pediatric pharmaceutical formulation of Met powder, to be reconstituted with water, to obtain a stable oral suspension. Organoleptic characteristics and physicochemical stability of the powdered Met formulation and suspension were evaluated at three storage temperatures. Met quantification was assessed by a stability-indicating chromatographic method as well as microbial stability. The use of a specific fruit flavor (e.g., strawberry) with sweeteners (e.g., sucralose) was considered acceptable. No drug loss, pH changes, microbiological growth, or visual changes were observed at 23 ± 2 °C and 4 ± 2 °C with the powder formulation for 92 days, and the reconstituted suspension for at least 45 days. The developed formulation facilitates the preparation, administration, the dose adjustment and palatability of Met treatment in children.

Occupational risks evaluation in a centralized antineoplastic agent preparation unit.

OBJECTIVE: The global professional risk assessment applied to the central unit of antineoplastic agent preparations is part of a mandatory approach required by the European legislation for workers. This study identified the hazardous situations related to the staff activity and then enabled the preparation of a formal plan of occupational prevention. METHODS: The nature of study approved by a working group constituted by experts was the global risk analysis. After identifying the hazardous situations, the global risk analysis estimated the risk level of each hazardous situation based on a criticality score, including severity and frequency. The global risk analysis highlighted the initial and residual risks after establishing a plan to reduce the high criticality risks. RESULTS: Hence, 33 unacceptable hazardous situations were identified. The critical categories of professional risks were "Product, emissions, and waste risks" with 17 (55%) hazardous situations; "Psychosocial risk factors" with 8 (24%) hazardous situations; and "Risks related to work equipment" with 6 (18%) hazardous situations. Once the risk reduction plan was in place, all hazardous situations were considered under control. The corrective actions led to a reorganization of human resources, the update of protection protocols, and optimization of ergonomic work tools. Staff-specific medical monitoring and regular surface contamination tests have been scheduled annually. In addition, initial and continuous training, specific to product and waste risks, has been updated. CONCLUSION: The global professional risk assessment related to centralized antineoplastic agent preparation unit generated failure in our system and enabled corrective actions for staff safety.