In use stability of chemical anticancer drugs and biologics

Background. For hospital pharmacists and nurses it is critical to have real data about the stability of injectable drugs in practical situations: opened drug formulation, after the reconstitution of lyophilized production or after the dilution in various vehicles. Unfortunately, these data are seldom available. The manufacturer’s stability data are usually quoted as “stable for 24 hours at 4 °C” not for the true reasons, but considering the possible bacterial contamination or due to the fact that stability tests were only conducted during a very short period. This problem is of paramount importance for therapeutic proteins, mainly monoclonal antibodies, because the latter are very expensive. Objective. To define the in use stability of anticancer drugs. Materials and methods. Analysis of literature data on this topic; own study on diluted rituximab stability. Results and discussion. Biologic drugs have revolutionized the treatment and prevention of many debilitating and life-threatening diseases. Biologics are much bigger and have a much more complicated structure than classical drugs. Principal causes of biologics’ instability include temperature changes, dilution, absorption, oxidation, shaking and shearing etc. Protein instability can be divided into physical and chemical instability. The former includes aggregation, denaturation and absorption on surfaces, and the latter – desamidation, disulfide bonds breakage and formation, oxidation, hydrolysis, isomerization, non-disulfide cross-linking, and deglycosylation. Instability of anticancer drugs and biologicals can lead to their toxicity, immunogenicity and efficacy loss. Instability can be overcome by the centralization of pharmacy handling, but firstly it needs to be thoroughly studied with the help of modern methods. The own study has revealed that the diluted rituximab is stable up to 6 months in polyolefin bags stored at 4 or 22 °C. The preparations can be realized without any problems. There also no fear of instability in case of thermal excursions. Such findings if introduced in practice can save about 150,000 euros a year. Conclusions. 1. In-use analysis of proteins requires several methods. 2. Instabilities are divided into physical and chemical. 3. Aggregation is an initial response to any stress and must be completely eliminated.