Compounding and Preparation of Parenteral Solutions and Medications

Document Purpose and Scope

This guideline establishes evidence-based standards for the safe compounding and preparation of parenteral solutions and medications in clinical settings. It is intended for use by nurses, pharmacists, and other healthcare professionals involved in intravenous therapy and applies to all care environments where parenteral medications are prepared or administered.

Foundational Standards

Regulatory Compliance

All compounding and preparation of parenteral solutions and medications must be performed in accordance with applicable laws, rules, and regulations established by governing regulatory and accrediting bodies within each jurisdiction, including national, state, and provincial requirements.

Sterile Product Preparation

Parenteral solutions and medications must be compounded and prepared using validated processes designed to produce and maintain a sterile product throughout preparation and administration.

Supporting Requirements

Three essential standards underpin all infusion-related procedures:

Resource Availability. Current references and resources pertaining to infusion medications and solutions must be readily accessible to clinicians at the point of care. This includes drug compatibility information, reconstitution guidelines, and administration parameters.

Patient Identification. A minimum of two patient identifiers—including the patient’s full legal name—must be verified prior to medication administration. For neonates and infants, distinct identification methods appropriate to the care setting should be employed to ensure accurate patient identification.

Aseptic Technique. Aseptic Non Touch Technique (ANTT®) must be applied consistently to all infusion-related procedures as a fundamental component of infection prevention practice.

Pharmacy-Based Compounding: The Preferred Standard

Rationale for Centralized Preparation

Whenever possible, medications should be compounded in a pharmacy environment that complies with established compounding standards and regulations. This recommendation is supported by systematic review evidence demonstrating that parenteral medications prepared in clinical environments carry a significantly higher risk of microbial contamination compared to those prepared in dedicated pharmacy compounding facilities (Larmené-Beld et al., 2019).

Medications Requiring Pharmacy Preparation

Certain medications warrant preferential preparation in the pharmacy setting due to their complexity or contamination risk. These include medications that require filtration during preparation, those susceptible to supporting microbial growth (such as lipid emulsions or concentrated dextrose solutions), preparations involving complex calculations, medications requiring dilution with extended dissolution times, and those with multistep preparation procedures or specialized reconstitution requirements. When feasible, such medications should be supplied to the clinical area in a ready-to-administer form to minimize manipulation at the point of care (Gabay et al., 2020; Institute for Safe Medication Practices, 2022).

Hazardous Drug Considerations

Compounding, reconstitution, or any manipulation of hazardous medications must not occur outside of an environmentally controlled hazardous drug preparation area. Appropriate engineering controls, personal protective equipment, and handling procedures must be maintained in accordance with established hazardous drug safety guidelines (Power et al., 2018).

Complex Compounding Requirements

When clinical circumstances require combining multiple medications in a single syringe for intravenous administration, or when more than three sterile products must be combined into a final preparation, this compounding should be performed in the pharmacy whenever possible. These complex preparations carry elevated risks for both calculation errors and microbial contamination (Institute for Safe Medication Practices, 2015).

Minimizing Manipulation: Principles for Reducing Error and Contamination Risk

Unnecessary manipulation of parenteral medications increases the risk of both dosing errors and microbial contamination. The following principles should guide practice.

Syringe Transfer Restrictions

Intravenous push medications must not be withdrawn from commercially available cartridge-type syringes and transferred into another syringe for administration. Once a medication dose has been measured in an appropriately sized syringe, it should not be transferred to a different syringe (such as a larger volume syringe) prior to administration. These transfers introduce opportunities for dosing errors, contamination, and medication waste (Degnan et al., 2020).

Dilution Practices

Unnecessary dilution of intravenous push medications should be avoided. Dilution is appropriate only when specifically recommended by the manufacturer or when required by organizational policies, procedures, or evidence-based practice guidelines.

Flush and Lock Solutions

Single-use, commercially prepared, prefilled syringes containing appropriate solutions should be used for flushing and locking vascular access devices. When multidose vials are used as a source for flush solutions, each vial must be dedicated to a single patient.

Preparation Procedures at the Point of Care

Environmental and Equipment Requirements

When medications must be prepared outside the pharmacy in immediate-use situations, preparation should occur in a clean area using appropriate aseptic fields in accordance with ANTT® principles. Appropriate precautions must be implemented to limit patient risk during bedside or unit-based preparation (Centers for Disease Control and Prevention, 2016; Council of Europe, 2016).

Syringe Selection for Accurate Dosing

Accurate measurement depends on appropriate syringe selection. The syringe chosen should be small enough to accurately measure the intended dose. For optimal accuracy, the selected syringe volume should be close to the desired dose volume, with the dose occupying at least 20% of the total syringe capacity (Jordan et al., 2021).

For hazardous drug preparation, syringe selection must also account for plunger stability. To decrease the likelihood of plunger separation from the syringe barrel, the dose should occupy no more than 75% of the syringe capacity when handling hazardous medications (Power et al., 2018).

Disinfection of Access Points

All critical access points—including vial stoppers, bag septa, and ampoule necks—must be disinfected prior to access. Physical and chemical decontamination is achieved by wiping these surfaces with 70% isopropyl alcohol. The disinfectant must be allowed to dry completely before needle entry into vials or bags, or before breaking of ampoules. This drying time is essential for achieving antimicrobial effectiveness.

Independent Verification

A second clinician should verify that the volumes and identities of all compounding ingredients—including any diluents—are correct before the ingredients are combined. When available, this verification should ideally be performed by a pharmacist who can remotely confirm the compounding process through video technology or review of still images. This independent double-check serves as a critical safety barrier against preparation errors (Institute for Safe Medication Practices, 2022).

Vial and Ampoule Handling

Preference for Closed Systems

Vials represent a closed system and should be used preferentially over ampoules, which are open systems, to decrease the risk of microbial contamination during medication withdrawal (van Grafhorst et al., 2002; Muller et al., 2010).

Ampoule Filtration Requirements

When medication must be drawn from an ampoule, a filter must be used during every withdrawal to prevent glass particulate contamination (Fry, 2015). A 5-micron or smaller filter straw or blunt fill filter needle should be used to withdraw medication from the ampoule. After medication withdrawal, any leftover medication must be immediately discarded along with the broken ampoule and the filter device.

The use of a blunt fill needle or filter straw rather than a standard filter needle reduces the risk of inadvertent administration through a contaminated filter device. If a needle is required for subsequent administration, the filter needle or filter straw must be discarded and replaced with a new, appropriate needle prior to administration. Under no circumstances should medication be infused or injected through a filter needle that was previously used to draw up medication.

Prohibited Practices for Compounding Supplies

Only supplies intended for compounding should be used in the preparation process. Intravenous solution containers intended for infusion—including minibags—must not be used as common-source containers for diluting or reconstituting medications. Similarly, prefilled flush syringes must not be used for medication dilution. The differences in gradation markings between flush syringes and standard syringes, combined with unchangeable labeling, potential partial loss of the drug dose, and contamination risks, significantly increase the likelihood of serious medication errors when syringe-to-syringe transfer occurs (Degnan et al., 2020).

Labeling and Timing Requirements

Immediate Labeling

Any medication that is prepared but not immediately administered must be labeled at the location of preparation without any break in the preparation procedure. During this process, all critical parts of the preparation system—such as injection needles and syringe tips—must be protected from contact with nonsterile surfaces, biological fluids, or particulate matter including aerosolized particles.

Beyond-Use Timing for Immediate-Use Preparations

For products prepared outside the pharmacy as immediate-use sterile preparations, administration must begin within 4 hours of preparation. If administration has not begun within this timeframe, the product must be discarded. This time limit reflects the increased contamination risk associated with preparations made outside of controlled pharmacy environments (United States Pharmacopeial Convention, 2023).

Single-Use and Multidose Vial Management

Single-Use Requirements

Compounding supplies must never be reused, whether for the same patient or different patients. Medications packaged as single-dose or single-use formulations are intended for use in only one patient. A new needle and syringe must be used for every entry into a vial or bag and for every injection. The same needle or syringe must never be used to administer medication to more than one patient (Dolan et al., 2016).

Multidose Vial Protocols

Multidose vials may be used for a maximum of 28 days after initial opening or first puncture, unless the manufacturer specifies a different beyond-use date. Following first use, the multidose vial must be labeled with the calculated beyond-use date, which must never exceed the manufacturer’s original expiration date.

Whenever possible, multidose vials should be dedicated to a single patient. When multidose vials must be used for more than one patient, they must never enter the immediate patient care area. If a multidose vial does enter the immediate patient care area, it becomes dedicated to that patient only and must be discarded after use for that patient (Centers for Disease Control and Prevention, 2016).

Competency and Education Requirements

Healthcare organizations must provide initial education and ongoing competency assessment—at minimum on an annual basis—for all clinicians involved in medication compounding and preparation. Research has identified that nurse medication administration skills require particular attention in the areas of medication preparation and administration technique (Luokkamäki et al., 2021).

Competency programs should address aseptic technique, appropriate syringe selection, disinfection practices, independent verification processes, ampoule handling with filtration, labeling requirements, timing limitations, and the proper use of single-dose and multidose vials.

References

Centers for Disease Control and Prevention. (2016). Guide to infection prevention for outpatient settings: Minimum expectations for safe care. U.S. Department of Health and Human Services. https://www.cdc.gov/infectioncontrol/pdf/outpatient/guide.pdf

Council of Europe. (2016). Resolution CM/Res(2016)2 on good reconstitution practices in health care establishments for medicinal products for parenteral use. https://www.edqm.eu/en/d/162941

Degnan, D. D., Bullard, T. N., & Hovda Davis, M. B. (2020). Risk of patient harm related to unnecessary dilution of ready-to-administer prefilled syringes: A literature review. Journal of Infusion Nursing, 43(3), 146–154. https://doi.org/10.1097/NAN.0000000000000366

Dolan, S. A., Arias, K. M., Felizardo, G., Barnes, S., Krein, S. L., Petersen, C., … & Schecter, W. P. (2016). APIC position paper: Safe injection, infusion, and medication vial practices in health care. American Journal of Infection Control, 44(7), 750–757. https://doi.org/10.1016/j.ajic.2016.02.033

Fry, L. (2015). Glass micro-particulate contamination of intravenous drugs—Should we be using filter needles? Australian Medical Student Journal, 6(1). https://www.amsj.org/archives/4271

Gabay, M., Hertig, J. B., Degnan, D., Dugan, L. L., Wilson, K., Gaughan, A. A., & Mirtallo, J. M. (2020). Third consensus development conference on the safety of intravenous drug delivery systems—2018. American Journal of Health-System Pharmacy, 77(3), 215–220. https://doi.org/10.1093/ajhp/zxz277

Institute for Safe Medication Practices. (2015). ISMP safe practice guidelines for adult IV push medications: A compilation of safe practices from the ISMP Adult IV Push Medication Safety Summit. https://www.ismp.org/sites/default/files/attachments/2017-11/ISMP97-Guidelines-071415-3.%20FINAL.pdf

Institute for Safe Medication Practices. (2022). ISMP guidelines for sterile compounding and the safe use of sterile compounding technology. https://www.ismp.org/resources/guidelines-sterile-compounding-and-safe-use-sterile-compounding-technology

Jordan, M. A., Choksi, D., Lombard, K., & Patton, L. R. (2021). Development of guidelines for accurate measurement of small volume parenteral products using syringes. Hospital Pharmacy, 56(3), 165–171. https://doi.org/10.1177/0018578719873869

Larmené-Beld, K. H. M., Frijlink, H. W., & Taxis, K. (2019). A systematic review and meta-analysis of microbial contamination of parenteral medication prepared in a clinical versus pharmacy environment. European Journal of Clinical Pharmacology, 75(5), 609–617. https://doi.org/10.1007/s00228-019-02631-2

Luokkamäki, S., Härkänen, M., Saano, S., & Vehviläinen-Julkunen, K. (2021). Registered nurses’ medication administration skills: A systematic review. Scandinavian Journal of Caring Sciences, 35(1), 37–54. https://doi.org/10.1111/scs.12835

Muller, A., Huisman, I., Roos, P., Grauls, A., Veltman, J., Roos, D., … & Voss, A. (2010). Outbreak of severe sepsis due to contaminated propofol: Lessons to learn. Journal of Hospital Infection, 76(3), 225–230. https://doi.org/10.1016/j.jhin.2010.06.003

Power, L. A., Coyne, J. W., & Hawkins, B. (2018). ASHP guidelines on handling hazardous drugs. American Journal of Health-System Pharmacy, 75(24), 1996–2031. https://doi.org/10.2146/ajhp180564

United States Pharmacopeial Convention. (2023). General Chapter <797> Pharmaceutical compounding—Sterile preparations. In USP-NF. United States Pharmacopeia. https://doi.org/10.31003/USPNF_M99925_07_01

van Grafhorst, J. P., Foudraine, N. A., Nooteboom, F., Crombach, W. H., Oldenhof, N. J., & van Doorne, H. (2002). Unexpected high risk of contamination with staphylococci species attributable to standard preparation of syringes for continuous intravenous drug administration in a simulation model in intensive care units. Critical Care Medicine, 30(4), 833–836. https://doi.org/10.1097/00003246-200204000-00019