This document discusses the risks of errors in preparing intravenous medications and argues that ready-to-use (RTU) drug preparations from industry according to Good Manufacturing Practices (GMP) standards can improve safety. It notes that intravenous medication preparation is complex and error-prone. Studies show preparation errors occur in 20-52% of cases in simulations and hospitals. RTU drugs prepared by industry in cleanrooms according to validated protocols and quality controls may reduce risks compared to hospital pharmacy preparation. While industry RTU drugs have higher initial costs, the document estimates they could save hospitals over $1,000,000 per year from avoiding serious adverse drug events and drug waste.

1. Leapfrogging into the injectables
drug market;
The case and pharmacoeconomics
of ready-to-use (RTU) drugs
James G. Boudreau
Kelowna Sales Meeting
June 10, 2014

2. FACTS
• Medication errors kill 7,000 people each year in the
United States To err is human, 1999
• Intravenous medication errors are nearly 3 times as
likely to cause harm or death compared with other
drugs routes (3% vs. 1.2%)
Am J Health-Syst Pharm 2008;65:2367-79
• The risk is related to the complexity of the process
and is froth with potential errors at every step
Risk = probability x consequences
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3. Intravenous medication:
a complex process
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4. Intravenous medication:
errors at each stage
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5. Preparation errors
Simulation study
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• Mean rate: 6.5% (n=28)
28%
52%
20%
Selection error
Dilution error
Quantity error
Garnerin Ph, Eur J Clin Pharmacol 2007;63:769

6. Preparation errors
Real-life study
• Unused syringes in anesthesiology
>± 10%: 29% >± 50%: 8% >± 100%: 4%
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Stucki C, HUG, 2009

7. Calculation errors
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• Nurses
26.7% (n=30)
• Anesthesiologists
10.4% (n=28)
Garnerin Ph, Eur J Clin Pharmacol 2007;63:769

8. Microbial contamination
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• Syringes contamination
• Intensive care units
in 6 hospitals (A-F)
• Pharmacy aseptic
unit (Ph(A))
Care Med 2002;30Van Garfhorst J, Crit :833-6

9. Houston, we’ve got a problem!
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10. Canadian approach to safety
Standardizing injectable drug dilutions and labelling
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Ready-to-use (RTU) preparations
From the industry
From the hospital pharmacy
Production Plant (GMP)
Outsourcing (Mixing/Compounding)
Aseptic Preparation
(Batching/Patient specific)

11. Ready-to-use (RTU) preparations
From the industry
Ready-to-use
• Clindamycin 50 mL bag
(Sandoz)
• 600mg & 900mg
• Potassium Chloride (KCl) bag
(Baxter)
• 500 & 1000 mL
• Cefazolin 100g bag (PPC)
• 2 liters
• Heparin bag (B Braun)
• 250 & 500 mL
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Outsourcing
• Pre-filled syringes
• Reconstitute powder vials
for:
• Bags, syringes,
intermate, pump
cassettes, etc.
• Prepare batch and/or patient
specific intravenous drugs

12. Ready-to-use (RTU) preparations
From the hospital pharmacy
• Collection of customer needs
• interested clinical areas
• list of potential drugs
• Risk assessment priority list
(probability of occurrence x consequences)
• Feasibility study
• Stability assessment
• Starting batch production
• Research industrial partnership
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13. Ready-to-use (RTU) preparations
Which is safer?
From the industry
• Good manufacturing practices
(GMP)
• Cleanrooms, laminar flow hoods,
operator qualification
• Documentation (standardized
production protocols)
• Working process (validation and
informatics)
• Quality control: standard operating
procedures (SOP)
• Traceability (whole process)
From the hospital pharmacy
• Lack of qualified personnel, room, funds,
and time
• Shorter shelf life due to drug stability
validation and testing
• Production protocols and procedures
(chemical)
• Computer-assisted production
management (chemical)
• Clean environment (microbiological)
• Specifically trained operators
(chemical, microbiological)
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• Operator ID
• password, facial recognition,
fingerprint
• Gravimetric weight
selection
• dosing by weight vs. volume
• Material ID
• barcode, photo label
identification
• Traceability
• metrics software
Computer-assisted production

15. Pharmacoeconomics
Hospital start-up costs for ready-to-use syringes
Investment costs
• Cleanroom Class C (ISO 7)
• (20 m2 x $12,000/m2) $240,000
• Filling machine
• Baxter Intellifill $600,000
• i.v.STATION $700,000
• Total (depending on filling system) $940,000
• 5 year amortization $188,000/year plus
• 5 year amortization w/o cleanroom $140,000/year plus
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16. Pharmacoeconomics
Hospital start-up costs for ready-to-use syringes
Development costs (stability study)
• Development and validation of a quantitative stability-
indicating analytical method
• Stability studies
• Total cost $14,800
• Cost / syringe $0.59
(5,000 syringes/year over 5 years)
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17. Pharmacoeconomics
Hospital preparation costs of ready-to-use syringes
Production costs ($) (Phenylephrine 1mg conc./1mL size)
Batch size 1,000 2,000 Nurse
• Vial unit price (1mL) $1.23 $1.23 $1.23
• Hood materials $1.18 $1.18
• Labour $1.48 $1.48 *$5.00
• Quality control $0.20 $0.10
– Total $4.09 $3.99 $6.23
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?
?
* 5 minutes/syringe
(Hecq JD, Ann Pharm Françaises 2011;69:30-7)

18. Pharmacoeconomics
Hospital benefits of ready-to-use syringes
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Risk Avoidance
• Pre-filled Phenylephrine syringes produced 400,000/year
• Error Rate 5% 20,000/year
• Ratio errors: serious ADE <1% 200/year
Bates D, J Gen Intern Med 1995;10:199
Cost per serious ADE $6,934 >$1,00,000/year
Leape L, JAMA 1999;281:267
Cost-saving
• Syringes discarded in anaesthesiology 50%
Weinger MB, J Clin Anesth 2001;13:491-7 $13.50/per syringe

19. Pharmacoeconomics
Bottom line
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Cost/syringe ($) (based on 400,000/year)
Pharmacy RTU Ward
• Investment $4.70
• Development $0.59
• Preparation $4.09 $6.23
• Risk management (safety) ? ?
• Cost-saving (waste) ? ?
Total (first 5 years) $9.38 $6.23
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5 years

20. Innovations for safety
Options
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RTU syringes/bags
(CIVA)
Robotized distribution Automated
dispensing
Electronic prescription
and patient record
Bedside scanning
Computerization Automation Robotisation Industrialisation

21. Conclusion
• The preparation of drug injectables
in hospital units is not reliable
• Ready-to-use (RTU) drugs improves
patient safety by changing the
paradigm
• A high quality assurance system
(GMP) is essential to ensure patient
and worker safety.
• Quality is paramount in a hospital
setting as it will save time, money
and ultimately…lives!
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