University hospitals and general hospitals were evenly represented among those who recently participated in a survey on RTU and RTA injections.
RTU (ready-to-use) is defined as an injection containing the active drug in solution at the required concentration and volume in a vial. The injection is transferred to a final container (syringe, infusion pump or elastomeric device) for administration to the patient. RTA (ready-to-administer) is defined as an injection containing the active drug in solution at the required concentration and volume, presented in the final container (syringe, infusion bag or elastomeric device), and is ready to be administered to the patient.
The majority of hospitals represented had between 500 and 1000 beds, and more than 75% of responders said that their pharmacy provided a centralised intravenous additive service (CIVAS).
The total number of items prepared each year varied hugely, divided evenly in each of the 0–1000, 1001–10,000, 10,001–25,000, 25,001–50,000 and >50,000 categories. There was a slight majority in the 1001–10,000 range.
For the 75% of responders whose pharmacies provided a CIVAS service, cytostatics represented nearly 50% of those prepared (see Figure 1).
For all preparations, 39% of syringe preparations numbered in their thousands, 53% of bag preparations numbered in the tens of thousands, and 43% of elastomeric device preparations numbered in their thousands.
Fifty-seven percent of all TPN preparations numbered in the thousands, 64% of all cytostatic preparations were in the tens of thousands, and 58% of all analgesic preparations were in the thousands.
Single injections were prepared for individual patients in 84% of cases. Sixty-three percent of responders did not prepare batches of injection for use by several patients but, for those who did, batch size was determined predominantly by the number of units prepared (49% of responders) as opposed to shelf life (26%), risk level of the process (20%) and whether it is used in house or supplied to other institutions (5%) (see Figure 2).
The top items prepared in batches included: heparin, cisplatin, fentanyl, bevacizumab, 5-fluorouracil, bortezomib, MabThera, clarithromycin, cefazolin, morphine, urokinase, carboplatin, vancomycin and levobupivacaine. Sometimes these were prepared in bags, sometimes in syringes.
Only 20% of responders had introduced dose-banding for cytostatics and, for these, a deviation from body surface area calculated dose of 5–10% was acceptable in 90% of cases: 10% allowed a 2.5% deviation, and no one allowed a deviation of greater than 10%.
The top cytostatics provided as dose-banded RTA products were: paclitaxel, fluorouracil, oxaliplatin, cyclophosphamide, carboplatin, gemcitabine, trastuzumab, mitomycin-C, irinoplatin and epirubicin.
Only 27% of respondents purchased RTU or RTA unlicensed injections from another hospital or a commercial compounding unit, 50% on a scale of 1–500 RTU vials annually (see Figure 3).
Forty-four percent of purchasers of RTA injections purchased as syringes, 44% as bags and 12% as elastomeric devices. Between 100 and 3000 TPN purchases were made, up to 6000 cytostatics and fewer than 50 analgesic preparations.
The top items purchased from a compounding unit were: bupivacaine (with fentanyl), methotrexate, oxaliplatin, epirubicin, ganciclovir, cycophosphamide and fluorouracil.
In contrast to purchasing trends from commercial compounding units, approximately one-half of respondents reported buying licensed RTU or RTA injections from pharmaceutical manufacturers, with a wide range of vial numbers (see Figure 4).
Sixty percent of responders purchase RTA injections as syringes, 30% as bags and 10% as elastomeric devices. Up to 6000 TPN RTA injection purchases were made each year, up to 2000 cytostatics purchases and no analgesic preparations.
The top RTU/RTA items purchased from pharmaceutical manufacturers were: dopamine, metronidazole, methotrexate, fraxiparine, heparin, enoxaparin, cyclophosphamide, Zometa, midazolam, vitcofol, ciprofloxacin, Fragmin and ropivacaine.
More than 80% of respondents stated that injections are still prepared on the wards of their institutions.
Nearly 60% of respondents indicated spare capacity to increase output from their aseptic units.
Of injections that are currently being prepared, just over 50% of respondents said that they would purchase if they became available as licensed products. The top RTU/RTA items that would be purchased include: fentanyl, methotrexate intrathecal, clarithromycin, piperacillin/tazobactam, vancomycin, vincristine, rituximab, ganciclovir, meropenem, bleomycin and mitomycin. Sometimes these were purchased in bags, sometimes in syringes.
Influences on the decision to choose RTU/RTA injections over traditional preparations are shown in Figure 5.