Simulating the risks of cross-contaminations relating to handling errors
The aim of our work was to search for risks of cross-contamination by simulating handling errors.
Equipment and methods
Observational analysis identified the risk situations in the manufacturing process leading to cross-contamination incidents. The four following risk situations were evaluated: re-use of a disposable transfer device: Syringe, Spike and 19 G Needle for 2 consecutive preparations of different active principles, and the use of a contaminated compress. Retinol, the lipophilic active principle (6mg/ml) was chosen as a marker to simulate paclitaxel. Simulation involved producing a 5 ml syringe with the marker followed by manufacturing of a syringe of p.p.i. water in which the marker is sought using a CLHP method with UV detection. The same process without the use of a marker served as a control.
The Retinol proportioning method was validated (as being linear, precise and true), the Detection Limit (DL) and Quantification Limit (QL) were respectively 0.3µg/ml and 1µg/ml. The following table shows the results for Retinol found in EPPI syringes.
For all control preparations (n=12), the quantity of Retinol found was < DL.
Discussion - Conclusion
Handling errors are potential sources of cross-contamination. Conversely, external surface contamination seems to have little impact on the risk of cross-contamination incidents. Calculation of the maximum admissible residue for paclitaxel (validation of cleaning methods ) in accordance with Fourman and Mullen’s formula gives a limit of 50 µg. This value is less than the results found that would justify this risk being taken into account. Automated dose banding preparation and production by campaign could allow this risk to be prevented.
 G.L. Fourman and M.V. Mullen, "Determining Cleaning Validation Acceptance Limits for Pharmaceutical Manufacturing Operations," Pharm. Technol. 17 (4), 54–60 (1993)