Pharmacy OneSource Blog

Negative Pressure Compounding. Written by Critical Point

Posted on 11/01/17

The concept of negative pressure compounding to prevent exposure of healthcare personnel the drugs being compounding was orignally introduced by Wilson and Solimando in 1981.[1]  They concluded that despite using a horizontal laminar airflow hood without additional precautions, their staff exhibited no evidence of mutagenicity. These results contributed to their utilization of negative pressure technique. By negatively pressurizing the vial, they were able to decrease or eliminate the leakage, spraying or aerosolizing of hazardous drugs (HDs) through the puncture in the vial septum. They also concluded that the use of vertical air-flow hood in conjunction with negative pressure technique provided a degree of environmental protection. This technique continues to be a fundamental principle in the preparation of compounded sterile hazardous medications today.

With the introduction of Closed System Drug Transfer Devices (CSTDs), referred to as Supplemental Engineering Controls in USP Chapter <800>, the practice of negative pressure technique has diminished, however, CSTDs are not available for ampules or all vials. The need for proper execution of negative pressure technique remains. Since CSTD use during compounding has been designated a best practice (a “should”) in USP Chapter <800>, not all HD compounding operations use these devices, so the need for negative pressure technique continues. 

As with all aseptic procedures, competency, and eventually proficiency are essential. Detailed standard operating procedures (SOPs) and careful training and documentation must occur. This document highlights the fundamental elements of negative pressure technique.

  • Perform all manipulation of HDs in Containment Primary Engineering Control (C-PEC) which is negatively pressured relative to the adjacent space and externally vented to the outside (refer to USP Chapter <800> for additional information)
  • Observe proper material handling practices before introducing any item into the ISO Class 5 C-PEC
    • Remove any unnecessary supplies
    • Decontaminate the deck between different types of HDs
    • Disinfect the deck with the sterile 70% IPA
    • Disinfect each component immediately before introduction to the C-PEC
    • Arrange items so not to impede first air
    • Open items to the left or right of Direct Compounding Area (DCA)
  • Vigorously swab the vial septum with sterile 70% IPA and allow to dry (CriticalPoint recommends 3 swipes with a critical site wipe in one direction to sanitize vial tops however there is no evidence-based research to validate this or any other method)
  • Perform manipulations in the Direct Compounding Areas (DCA) and in a way in which critical sites remain in unobstructed HEPA filtered air (also called First Air)
  • Use a syringe that is 25% larger than the total dose
  • Carefully attach the needle and syringe being careful to avoid touch contamination of either critical site
  • Draw up the amount of air that is equal to the total dose to be drawn up
  • Insert the need into the septum being mindful of the first air coming down from the top of the C-PEC so hold the vial and needle/syringe assembly slightly horizontally
  • Without touching the barrel and with the needle above the fluid level, pullback on the plunger slightly to create a negative pressure within the vial
  • Invert the vial (but again keeping in mind first air so less than vertical) and with needle below the fluid level, withdraw no more than 15-25% of the dose into syringe, until you feel resistance. Slowly transfer small amounts of the medication into the syringe as equivalent amounts of air are exchanged for fluid.
  • Each time allow the syringe plunger to return to original position and never let plunger go ABOVE that original position (whatever the total dose volume is), otherwise this can result in positive pressure which is often the cause of leaking of HD residue or vapor.
  • Repeat these steps until the total volume is drawn up. This may need to be repeated many times. You will gradually replace the volume of air in the syringe with the HD drug.
  • With the needle still in the vial, remove all air bubbles and adjust to the final dose.
  • Once the final dose is measured, place the vial upright on the deck and withdraw a slight amount of air through the needle to clear the hub of the syringe of drug. NO additional air should be drawn into the syringe. The hub must be clear so that when the CSTD is attached, no drug leaks. Remember USP <800> requires the use of CSTDs for administration when the dosage form allows so the final dose must leave the pharmacy ready for administration.
  • Carefully withdrawal the needle and syringe from the vial.
  • Follow proper material handling procedures for removing hazardous compounded sterile preparations for the C-PEC.

If you are not using CSTDs for compounding, it is your responsibility to ensure your compounding personnel understand and properly use negative pressure technique. Consider using visual tracers (such as red fluid or fluorescent dyes) to provide visual feedback during training.  Better yet, move to CSTDs for compounding too. We think it takes 3 to 5 times longer to draw up a dose using proper negative pressure technique than it does when a CSTD is used.

This article was published in CriticalPoint Pearls in September 2017.

[1] Wilson, JP and Solimando DA. Aseptic technique as a safety precaution in the preparation of antineoplastic agents. Hosp Pharm. 1981. Nov; 16(100): 575-6, 579-81.

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About the Author

CriticalPoint monthly Sterile Compounding Pearls of Knowledge are written by a team of leading industry experts. Each author has dedicated their career to teaching industry standards and best practices. To read about each of our experts visit www.criticalpoint.info/about-us/our-faculty-experts. The monthly topics are based on frequently asked questions asked by you and your colleagues and cover all aspects of the pharmacy. You can find our current and archived Pearls at www.criticalpoint.info/tools-resources.