Cytotoxics compounded sterile preparation control by HPLC during a 16-month assessment in a French university hospital: importance of the mixing bags step

Abstract

The Centralized Chemotherapy Reconstitution Unit (CCRU) of Paul Brousse Hospital Pharmacy Department assessed the reliability of its Cytotoxics Compounded Sterile Products (CCSP) preparation method in order to improve its CCSP quality assurance system. Five cytotoxic drugs — gemcitabine, 5-fluorouracil, docetaxel, paclitaxel, and oxaliplatin — were assayed by high performance liquid chromatography (HPLC) to determine CCSP concentration. During the observation period, 23,892 CCSP were prepared. Overall, 12,964 preparations contained one of the five analyzed drugs; 7382 (56.9%) out of 12,964 CCSP were analyzed by HPLC; 646 (8.8%) out of 7382 concentrations were outside ± 20% of the prescribed dose; 544 (84.2%) out of 646 were post-administration results and could not be verified. Out of 102 (15.8%) pre-administration results that were re-tested after re-shaking, 94 (92.2%) were found to be acceptable upon re-testing, and 8 (7.8%) were confirmed to be unacceptable and needed to be re-compounded. The 8.8% of tested CCSP were outside ± 20% of the prescribed dose, but extrapolating the results on re-tested CCSP, we can say that our CCSP preparation is reliable with an estimation of only 0.7% of 7382 CCSP analyzed, confirmed as being ± 20% outside the prescribed dose. Nevertheless, this ± 20% magnitude of error should be reduced. Based on pre-administration results, the primary cause of concentration errors appeared to be insufficient mixing of the finished product. Most CCSP dosages occurred after it had been administered, the organization should, therefore, be improved to include testing all CCSP prior to administration. Pharmaceutical companies should endeavor to manufacture compounded injectible drugs in a ‘ready to use’ form and provide vehicles in accurate volumes in order to improve compounding precision.

2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, Including Standards for Pediatric Oncology

“…The health care setting has policy to document the qualifications of clinical staff who order, prepare, 14 and administer chemotherapy 15-21 and documents: The health care setting uses a comprehensive education program for initial and ongoing educational requirements for all staff who prepare and administer chemotherapy.…”

Determination of 16 antineoplastic drugs by capillary electrophoresis with UV detection: Applications in quality control

“…These preparations were not rejected by in-process control. These divergences might indicate a mixing issue during preparation, which is a critical step for quality control as already mentioned in another study [7]. Error bars representing the confidence interval were too small to be represented (lower than 3.5% for both methods)…”

“…Moreover, not all antineoplastic drugs have spectrophotometric/spectroscopic properties. Therefore, separation techniques principally based on chromatographic separation such as thin‐layer chromatography and liquid chromatography (LC) appeared as attractive alternatives . Their high selectivity due to the wide choice of mobile and stationary phases constitutes their primary advantages.…”

Analytical Control of Pediatric Chemotherapy Preparations with a UV-Raman Automaton: Results After 18 Months of Implementation and Development of A Suitable Method for Low Volume Preparations

“…It could be interesting to assess the financial cost of this impossibility of achieving a second sample. Excluding NC due to the assay method (low analytical sensitivity for small concentrations), false NC is usually due to poor homogenization as also noticed by Castagne et al [22] where 92.2% of second control was conform after shaking. The bad homogenization of preparations is especially important because it generates a significant loss of time.…”

“…The overall conformity rate was 94.4% or 5.6% of NC. This result, corresponding to an implementation of the [11,22].…”