3PC-039 Early de-risking of the stability of a personalised, sterile bacteriophage suspension on the basis of advanced kinetic modelling

Background and Importance Bacteriophages, natural viruses of bacteria, are a promising therapy against multidrug-resistant bacteria. The use of therapeutic bacteriophages (TBP) requires the selection of the most active ones and their individual formulations (hospital or magistral preparations) by a hospital pharmacy for a personalised medicine. The risk of TBP instability must be managed at the earliest stages of development. Aim and Objectives Advanced Kinetic Modelling reliability assessment to de-risk the instability of BPT formulations. Material and Methods A purified anti-staphylococcal BP (Silviavirus) formulated in two solutions (A and B) was tested. The main critical quality attribute to assess their stability was the biological activity, determined by numeration of Plaque Forming Unit (PFU) (Spot Test), with a target set at (10 ± 9).10⁸ PFU/mL. The following study designs were performed: (i) an accelerated degradation with seven temperature conditions (from -80 °C to +50 °C) during 3 months (analysis at D0, D7, D14, D28, D60, and D90), the data generated being used for AKM with PREDISTAB method; (ii) a prospective stability study based on spot test performed (n=3) at 5 and 25 °C during 12 months for A and 6 months for B. Results The results (expressed in PFU/mL) of the prospective vs predicted stability studies were as follows: for solution A ⁸ vs 2.43x10⁸ (DLOG=0.66%) and 1.04x10⁵ vs 2.65x10⁵ (DLOG=8.1%) ⁸ vs 1.46 x10⁸ (DLOG=2.05%) and 3.56x10² vs 4.76x10² (DLOG=4.94%) for solution B at 5° and 25°C after 6 months: 2.56x10⁸ vs 5.60x10⁸ (DLOG=4.04%) and 1.67x10⁴ vs 2.69x10³(DLOG=18.78%) Conclusion and Relevance Our data suggest that AKM allows rapid assessment of the risk of instability for both formulations. Comparison of the results of the predictive vs prospective stability studies showed a good precision at 5 °C and 25 °C during 12 months for formulation A and 6 months for formulation B. The prospective study is still ongoing for both formulations to be compared with predictions at 24 months. The PREDISTAB method by identifying the risk of instability at the earliest stage of development should allow the early selection of the best TBP formulation and predict the expiry date. References and/or Acknowledgements Conflict of Interest No conflict of interest.