Development of a flowchart for risk assessment and allocation of preparation of monoclonal antibodies.

Monoclonal antibodies have expanded as a novel class of therapeutic agents. In contrast to appropriate guidelines for safe handling of cytotoxics, there are no real standards for the safe handling of monoclonal antibodies. Many questions have arisen whether monoclonal antibodies have to be prepared under controlled circumstances or can be prepared on the ward. We developed a flowchart which provides recommendations for the classification of monoclonal antibodies according to their toxicity profile and takes practical and financial issues into account. It allows oncology pharmacists worldwide to define which monoclonal antibodies can/must be prepared in pharmacy aseptic facilities and which monoclonal antibodies can be prepared on the ward.

The impact of logarithmic dose banding of anticancer drugs on pharmacy compounding efficiency at Ghent University Hospital.

BACKGROUND: Dose banding (DB) (dose rounding with predetermined variation with prescription) enables in-advance preparation of high-turnover anticancer drugs with potential benefit for pharmacy compounding work flow. OBJECTIVES: To analyse the impact of potential situations on the efficiency of DB in the pharmacy (safe and maximum storage), calculate preparation lead times and the potential full-time equivalent (FTE) benefit. METHODS: Candidate intravenous anticancer drugs were selected for logarithmic DB according to prescribing frequency, infusion volume and stability (usage data 2015 of the tertiary Ghent University Hospital, Belgium). With a selected DB set already stored, a 2-week time study (April/November 2015) provided lead times (between prescription and transfer) for just-in-time and DB preparations. A 'maximal' storage (using all drugs with a relative incidence of ≥2% recurrent monthly prescription) and a 'safe' storage scenario (lowest monthly prescribing pattern) were used to calculate the potential future FTE change. RESULTS: Mean lead times for DB storage and just-in-time preparation were 17.1 min (95% CI 13.5 to 21.0) and 26.5 min (23.3 to 29.8). For 21 164 yearly preparations with already 5292 in DB (25%), 11 157 and 6 862 could be batch-produced in advance in a maximum storage and safe storage scenario, respectively. The existing FTE in 2015 of 5.41 could then be reduced to 4.91 and 5.27. CONCLUSION: Further development of DB could contribute to pharmacy compounding efficiency.

Investigation of active pharmaceutical ingredient loss in pharmaceutical compounding of capsules.

Pharmaceutical compounding of capsules is still an important corner stone in today's health care. It allows for a more patient specific treatment plan as opposed to the "one size fits all"-approach, used by the pharmaceutical industry when producing fixed dose finished drug products. However, loss of active pharmaceutical ingredient (API) powder during pharmaceutical capsule compounding can lead to under-dosed finished drug products and annul the beneficiary therapeutic effects for the patient. The amount and location of API loss was experimentally determined during capsule compounding of five different preparations: 10 and 20mg hydrocortisone capsules, 4mg triamcinolone capsules and 0.25mg dexamethasone capsules, using a 10% m/m self-made or commercial trituration. The total API amount present in the five capsule preparations varied between 90.8% and 96.6%, demonstrating that for certain preparations, significant API mass loss occurred during the pharmaceutical compounding of capsules. Swabbing results of the different compounding equipment and working areas indicated the mortar surface as the largest API loss location. An agate mortar accounted for the least amount of API loss, whereas an extensively used porcelain mortar accounted for the highest amount of API loss. Optical microscopy and roughness (Ra) determination by profilometry of the different mortar surfaces revealed a significant influence of the mortar surface wear and tear on the observed API loss. This observation can be explained by physical deformation, or scratch formation, of the relatively soft porcelain mortar surface, in which the API particles can become adsorbed. Furthermore, a small effect of the capsulation device material on the API loss was also observed. The presence of a chemical molecule effect on the API loss was demonstrated through data mining using a set of assay results containing 17 different molecules and 1922 assay values. The 17 median assay values were modeled in function of corresponding molecular descriptors, using stepwise multiple linear regression. The obtained MLR model, containing RDF060m, R6e(+) and R3m(+) variables, explained 92.5% of the observed variability between the 17 median assay values.

Stability of extemporaneously prepared cytarabine, methotrexate sodium, and methylprednisolone sodium succinate.

PURPOSE: The short-term stability of extemporaneously prepared triple intrathecal therapy, containing cytarabine, methotrexate sodium, and methylprednisolone sodium succinate, was evaluated. METHODS: Three batches of triple intrathecal solution were prepared using commercially available products and stored in three different packaging materials (plastic syringe system, brown glass vials, and brown glass vials filled with metal needles). The solutions were protected from light and stored at 5 °C, 25 °C, and 40 °C or exposed to ultraviolet and visible light at 25 °C, compliant with the International Conference on Harmonisation. Samples were taken immediately before and after 4, 8, 24, 32, and 48 hours of storage. Simultaneous high-performance liquid chromatography- ultraviolet light/diode array detector assay of cytarabine, methotrexate sodium, and methylprednisolone sodium succinate was performed using a fused-core stationary phase and an acetonitrile-based gradient. First-order kinetic degradation values were calculated, and temperature dependence was evaluated using the Arrhenius equation. RESULTS: Cytarabine was stable under all storage conditions. Methotrexate sodium displayed significant degradation after light exposure but remained stable under the other storage conditions. Methylprednisolone sodium succinate was found to be the most labile component in the triple intrathecal solution. Temperature-dependent degradation was observed, resulting in 46% degradation after 48 hours at 40 °C. Two degradants were formed: methylprednisolone and methylprednisolone hydrogen succinate. Packaging material and batch-to-batch variability did not significantly influence the stability of the triple intrathecal solution. CONCLUSION: Triple intrathecal solution of cytarabine, methotrexate sodium, and methylprednisolone sodium succinate was stable for up to 12 hours when stored at 5 °C and protected from light.