Until the 2019 revision of USP General Chapter <797>, the reconstitution of drug vials was compounding (low-risk level) and within the scope of the chapter.1 This inclusion is no longer true in the revision,2 creating a potential patient safety risk. Every package insert extolls the virtue of using aseptic technique when reconstituting the vial. What is aseptic technique? Aseptic technique can be defined as a set of specific work practices and procedures performed under carefully controlled conditions to minimize the introduction of contamination. The Centers for Disease Control and Prevention (CDC) defines it as the manner of handling, preparing, and storing of medications and injection equipment/supplies (e.g., syringes, needles and I.V. tubing) to prevent microbial contamination.3
As a practical matter, what work practices and procedures are required of a practitioner when they reconstitute a drug vial? There aren’t well-established work practices and procedures routinely practiced by healthcare practitioners.4,5
USP Chapter <797> emphasizes the important role that compounding personnel play—especially through aseptic technique or how they use their hands—in preventing inadvertent contamination of compounded sterile preparations (CSPs) during preparation.1 The introduction to Chapter <797> states, “It is generally acknowledged that direct or physical contact of critical sites (e.g., vial septa, syringe and needle hubs, and injection ports) of CSPs with contaminants, especially microbial sources, poses the greatest probability of risk to patients.”1 Unfortunately, not all compounding personnel realize that improper aseptic technique can lead to microbial contamination and medication errors.
Two decades ago, CDC published evidence-based guidelines on safe injection practices.6 These practices focused on critical elements of aseptic technique to prevent healthcare-acquired infections. Several outbreaks have occurred when robust safe injection practices were not followed.4,5
Several studies have repeatedly identified human-borne contamination as the greatest threat to the sterility of CSPs, making this the most critical factor to be controlled during aseptic processing.7-9 Trissel et al.9 demonstrated that critical work practices employed in pharmacy settings, such as donning sterile gloves and routinely disinfecting gloved hands with isopropyl alcohol, reduced the rate of contamination of media fills from 5.2% to 0.3%.
In other countries around the world, it is routine for nursing to prepare all compounded medications except parenteral nutrition and chemotherapeutic medications. In 2019, Larmené-Beld, Frijlink, and Katja10 conducted a systematic review and meta-analysis to evaluate the contamination rate of parenteral medications in hospitals prepared in a pharmacy environment and a clinical environment in Europe from 2000-2018. They found significantly higher contamination rates when the preparation of parenteral medication occurred in the clinical environment compared with the pharmacy environment. The point estimates (random effect model) for the overall contamination rate of doses prepared in the clinical environment was 7.47% (5.16–9.79%) and 0.08% for doses prepared in the pharmacy environment.
Reconstitution Outside of the Pharmacy
There are several areas in the hospital outside of the pharmacy where drug vial reconstitution could occur and where aseptic technique is paramount, such as in imaging (including interventional radiology and cardiac catheterization lab), operating suites (including preoperative, perioperative, and post-anesthesia care units), emergency department, and patient care units. Pharmacists and technicians should serve as an educational resource and provide instruction in proper aseptic technique to those healthcare professionals also preparing medications.
Since these professionals will not be working within an ISO Class 5 primary engineering control, their elements of performance for proper aseptic technique should include the following:
- Personnel must perform hand hygiene procedures and don sterile gloves and other garb required by organizational policy before using a sterile needle and syringe to prepare or administer any medication or fluid.
- All work surfaces should be disinfected before performing any aseptic manipulation.
- Never reuse a needle or syringe that has been used for another patient. Cleanse the vial septa, injection port, or the neck of an ampule with sterile 70% alcohol before accessing the container with a needle and syringe.
- When possible, use single-dose vials and discard immediately after use.
- Use a new sterile needle and syringe each time a multiple-dose vial is accessed and avoid touch contamination of the needle and syringe before penetrating the vial septa.
- After use, multiple-dose vials need to be dated and then discarded 28 days after opening, unless otherwise specified by the manufacturer.1,2
- Refrigerate vials after they are opened if recommended by the manufacturer.
- Discard any vial, ampule, or bag if sterility is compromised or questioned. Do not use any container that has visible turbidity, leaks, cracks, or particulate matter, or if the manufacturer’s expiration date has passed.
- Never combine leftover contents of single-use vials for later use.
- Never leave a needle in place in the vial diaphragm.
- Do not remove pharmacy bulk packages or vials spiked with a dispensing pin from the ISO Class 5 primary engineering control.
These basic elements of performance for aseptic technique can positively impact the effort to prevent healthcare-associated infections and ensure patient safety.11 Identify the hospital departments where reconstitution of medication vials may occur and who can benefit from the expert knowledge and resources of pharmacists and technicians in the principles of aseptic technique and contamination control. By understanding and then teaching adherence to the elements of performance for proper aseptic technique, you can ensure medication safety throughout your organization.
- The United States Pharmacopeial Convention. Chapter <797> pharmaceutical compounding—sterile preparations. United States Pharmacopeia 31/National Formulary 26. First supplement official date, June 1, 2008.
- The United States Pharmacopeial Convention. General chapter <797> pharmaceutical compounding—sterile preparations. In: USP Compounding Compendium. https://www.usp.org/compounding/general-chapter-797 (accessed 2019 Aug 8).
- Centers for Disease Control and Prevention. Injection safety, FAQs regarding safe practices for medical injections. https://www.cdc.gov/injectionsafety/providers/provider_faqs_general.html (accessed 2019 Aug 8).
- MacCannell T, Perz JF, Srinivasan A, Schaefer MK. Bacterial and parasitic infections associated with extrinsically contaminated injectable medications, United States 1999–2009 [Abstract]. Presented at the Fifth Decennial International Conference on Healthcare-Associated Infections. Atlanta, GA; 2010 Mar 20. Available at: https://shea.confex.com/shea/2010/webprogram/Paper2113.html (accessed 2019 Aug 8).
- Perz JF, Thompson ND, Schaefer MK et al. US outbreak investigations highlight the need for safe injection practices and basic infection control. Clin Liver Dis. 2010; 14:137–51.
- O'Grady NP, Alexander M, Dellinger EP et al. Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2002 Aug 9;51(RR-10):1-29.
- Trissel LA, Gentempo JA, Anderson RW, Lajeunessee JD. Using a medium-fill simulation to evaluate the microbial contamination rate for USP medium-risk-level compounding. Am J Health-Syst Pharm. 2005; 62:285-8.
- Thomas M, Sanborn MD, Couldry R. I.V. admixture contamination rates: traditional practice site versus a class 1000 cleanroom. Am J Health-Syst Pharm. 2005; 62:2386-92.
- Trissel LA, Gentempo JA, Saenz LM, Woodard MY, Angeles CH. Effect of two work practice changes on the microbial contamination rates of pharmacy-compounded sterile preparations. Am J Health-Syst Pharm. 2007; 64:837-41.
- Larmené-Beld KHM, Frijlink HW, Taxis K. Eur J Clin Pharmacol. 2019; 75:609-17. doi: 10.1007/s00228-019-02631-2.
- Austin P, Elia M. Improved aseptic technique can reduce variable contamination rates of ward-prepared parenteral doses. J Hosp Infect. 2013; 83:160–3.