(M1030-08-43) Quality Assurance Practices for Transportation of Oncology Treatments: The Case Study of Drones

Purpose: Monoclonal Antibodies (mAbs) are frequently prescribed by oncologists for cancer patients. Whilst highly effective, these medicines have very short expiries and are administered in patient specific doses, clinical deterioration and supply chain disruption can often lead to wastage, and there is a need to improve efficiency in the logistics practices between manufacturing sites and administration locations. This study aimed to develop new quality assurance practices for cancer treatments by evaluating the first reported drone flights of mAbs.

Methods: Clinically expired premanufactured mAbs were investigated, contained inside instrumented Versapaks and flown in a Skylift Mugin V50 vertical take-off and landing drone through seven phases of flight, (take-off, hover, transition, cruise, transition, hover, and landing). Storage specifications (2-8°C) were met, and any vibrations emanating from the drone and transmitted through the packaging during flight were carefully monitored using accelerometers. The stressed samples were analysed for structural integrity by dynamic light scattering (DLS) and size exclusion, high performance liquid chromatography (SE-HPLC). The approaches used were considered as reference methods in the stability assessment of biopharmaceutical products (ICH Q5C & Q5E) NHS Standard Protocol for Deriving and Assessment of Stability (Santillo et al. 2019). Overall vibration levels were obtained using the standard deviation of the magnitude of the resultant acceleration vector, i.e., the square-root of the sum of the variances of the signals in the three orthogonal directions. Octave band spectra were synthesised by first computing the narrowband spectra and summing them in each octave band.

Results: Vibration occurred largely in the 63 Hz octave band (44-88 Hz) which was consistent with rotor speeds during operation and was significantly greater in amplitude during transition than in forward flight or in hover. Bench experiments validated assurance practices by exploring the edge of quality failure by applying extremes of rotational vibration to the mAbs. Aggregation, fragmentation, and the presence of microbial particulate matter represent the loss of mAb quality and are a risk to patient safety. No significant difference was identified in the aggregation and fragmentation of all flown samples, indicating structural integrity. Flown mAbs in their infusion bags had similar particle sizes compared to controls, (Bevacizumab 11.8±0.17nm vs. 11.6±0.05nm, Trastuzumab 11.2±0.05nm vs. 11.3±0.13nm, Rituximab 11.4±0.27nm vs. 11.5±0.05nm) and aggregate (High Molecular Weight Species, HMWS) content (Bevacizumab 1.25±0.03% vs 1.32±0.02% p=0.11, Trastuzumab 0.15±0.06% vs. 0.16±0.06% p=0.75, Rituximab 0.11±0.02% vs. 0.11±0.01% p=0.73).

Conclusion: The quality of the three mAbs was assured, suggesting that the V50 drone did not induce sufficient levels of vibration to adversely affect their quality. The findings of this paper, the improvements in quality assurance and the framework developed therein, will facilitate these investigations into sustained flight.

References: Santillo M, Davies L, Autsin P, Campbell C, Castano M, Marks C, et al. Standard Protocol for Deriving and Assessment of Stability – Part 2: Aseptic Preparations (Biopharmaceuticals) [Internet]. NHS; 2021.

Acknowledgements: Funding Information: FTZ & eDrone - NUMBERS
The authors would like to thank the Isle of Wight NHS Trust team and Portsmouth Pharmacy Manufacturing unit for their support in this investigation, and for supplying expired medicines which would otherwise have been disposed of. Additionally, the authors thank Apian Ltd. for facilitating the flights featured in this paper.


Figure 1. Study design: sample preparation and packaging for the trial (a) Skylift Mugin V50 drone; (b) Loaded 18 L Versapak; (c) 18 L Versapak with insulated cool packs, sensors, and samples; (d) Sample information and preparation process.


Figure 2. Summary of (a) DLS and (b) SE-HPLC result of Bevacizumab at different storage conditions, samples flown in different volume are used for headspace studies. All values were expressed as the mean of 3 tests ± SD deviation. The stability tested by DLS is expressed as: stable (quality maintained), × not stable. The SE-HPLC peak area of aggregates (HMWS) and fragments (LMWS) is shown in percentage. A one-way analysis of variance (ANOVA) tests and Student’s t-tests (two-tailed) were undertaken.


Figure 3. Methodology flow diagram for the validation or novel transport modes to assure quality of medicines.