Sterile Compounding: A Guide for Community Pharmacists

After reading this article you will:

• understand the principles of sterile compounding
• understand the requirements for sterile compounding
• understand the principles of operation of a laminar airflow hood

Introduction

Sterile compounding plays an important role in preparing medications that must remain sterile, including certain injectable, intravenous, ophthalmic, and other preparations. Because contamination or compounding errors can create serious risks for patients, sterile preparations require appropriate facilities, equipment, procedures, and trained personnel.

In the United States, USP General Chapter <797> establishes standards for compounded sterile preparations (CSPs), including requirements related to personnel, facilities, engineering controls, environmental monitoring, cleaning and disinfection, and other aspects of sterile compounding.

A key part of sterile compounding is maintaining an appropriate controlled environment around the critical compounding process. Primary engineering controls (PECs), including equipment such as laminar airflow workbenches (LAFWs), are used to provide the controlled environment needed for sterile compounding.

For community pharmacies involved in sterile compounding, understanding these principles is important for contamination control, proper workflow, and patient safety. This guide introduces key sterile compounding concepts and explains the role of laminar airflow workbenches in preparing compounded sterile preparations.

Background

Sterile compounding requires appropriate practices, facilities, equipment, and procedures to help protect compounded sterile preparations from contamination and other quality risks. In the United States, USP General Chapter <797> establishes minimum standards for compounded sterile preparations (CSPs) and addresses risks including microbial contamination, excessive bacterial endotoxins, variability in intended strength, unintended contaminants, and ingredients of inappropriate quality. Community pharmacies performing sterile compounding should also follow applicable federal, state, and local requirements.

Aseptic Preparation Area

A sterile compounding service in a community pharmacy can be established and operated within a reasonably small area if it is well planned and organized. The aseptic preparation area may be a separate room or located in a low or controlled traffic area with limited access. Ideally, the area should be adjacent to the dispensary, clean, and free from excess clutter and debris. The aseptic preparation area should be designed and operated in accordance with applicable sterile compounding standards and requirements.

A laminar airflow hood is essential for the preparation of sterile products and should be located in the aseptic preparation area. Storage shelves, refrigerators, sinks, etc., should be located in a separate adjacent area to help reduce possible contamination. Inventory in the aseptic area should be kept at minimal levels and no exterior packaging of pharmaceuticals should be present. Materials such as needles, syringes and alcohol swabs can be kept in the preparation area but only at minimal levels. Activities such as gowning/gloving (if needed), handwashing, and disinfecting should be done in a separate support area with clear, posted guidelines and procedures.

Laminar airflow hood

Sterile compounding should be performed within an appropriate primary engineering control (PEC), which may include a laminar airflow workbench (LAFW), depending on the compounding application. These hoods are designed to reduce the risk of airborne contamination during the preparation of sterile products.

Laminar airflow hoods have two basic functions:

1. To filter bacteria and exogenous materials from the air.
2. To maintain constant airflow out of the hood to prevent contaminated room air from entering the hood.

The hood functions as a high-efficiency dual filtering system. Air is taken into the unit and passes through a prefilter, removing gross contaminants such as dust or lint. The prefilter is very similar to those found in household furnaces. It is easily removed and can be cleaned by washing or vacuuming the particles. It should be checked periodically and replaced if needed.

After passing through the prefilter, the air is channeled through the high-efficiency particulate air (HEPA) filter to remove fine bacterial contaminants. This filter is built into the hood and is responsible for the sterile environment in the hood. The HEPA filter is not easily removed and generally requires outside maintenance for cleaning (4).

Airflow velocity determines the filtering capacity of the hood. If the airflow is reduced, the filter is presumed to be clogged with contaminants and must be cleaned.

Modern sterile compounding environments are classified using ISO air cleanliness standards. Primary engineering controls used for sterile compounding are designed to provide an ISO Class 5 environment at the critical compounding area. Appropriate airflow, HEPA filtration, equipment placement, and certification are important for maintaining the required air quality.

There are two types of laminar airflow hoods available for compounding non-toxic sterile products:

1. Horizontal Air Flow. HEPA-filtered air moves horizontally across the work area toward the operator. This unidirectional airflow helps protect the critical compounding area from contamination.

2. Vertical Air Flow. HEPA-filtered air moves vertically downward across the work area. Both horizontal and vertical laminar airflow workbenches can provide the controlled ISO Class 5 environment required for appropriate sterile compounding applications.

When working under a laminar airflow hood, these guidelines should be followed to ensure proper use: (5, 6)

1. The primary engineering control (PEC) should be operated according to the manufacturer’s instructions and the facility’s established procedures. If the PEC has been turned off, it should be operated for the manufacturer-specified recovery time before compounding begins.
2. The interior surfaces of the PEC should be cleaned and disinfected according to the facility’s established procedures and applicable sterile compounding requirements, using appropriate cleaning and disinfecting agents.
3. Items introduced into the PEC should be disinfected with sterile 70% isopropyl alcohol (IPA) using a sterile low-lint wiper and allowed to dry before use.
4. Objects placed in the PEC should be positioned to maintain unobstructed unidirectional airflow and avoid disrupting first air to critical sites. Work should be performed within the designated direct compounding area according to the PEC manufacturer’s instructions and applicable procedures.
5. The PEC should be certified at least every 6 months and whenever required after relocation, major service, or other changes that could affect its performance.
6. Personnel performing sterile compounding should follow applicable hand hygiene and garbing requirements before entering the compounding area and beginning compounding activities. Required garb should be worn in accordance with applicable sterile compounding standards and the facility’s established procedures.

Aseptic technique

Aseptic technique includes practices used to minimize the risk of microbial contamination during sterile compounding. Contamination may be introduced by personnel, equipment, supplies, or the surrounding environment, so these potential sources must be controlled during preparation. Key practices include:

1. Personnel should perform hand hygiene in accordance with applicable sterile compounding requirements before beginning compounding activities and when required after leaving and re-entering the compounding area.
2. Personnel should wear the required garb for sterile compounding in accordance with applicable standards and the facility’s established procedures.
3. Activities unrelated to product preparation should be kept to a minimum.
4. Eating or drinking, or the storage of food, drinks, or personal items should not be allowed in the aseptic area.
5. Personnel working within or around the PEC should minimize unnecessary movement and activities that could disrupt unidirectional airflow or introduce contamination into the direct compounding area.
6. All items that will be used during preparation should be checked for defects and expiry dates prior to use.
7. Non-sterile items introduced into the PEC should be disinfected using an appropriate method before being placed in the direct compounding area.
8. Only items necessary for the compounding procedure should be placed in the PEC, and they should be arranged to avoid obstructing first air or unidirectional airflow.
9. Direct contact between a sterile product and any non-sterile product should be avoided.
10. Critical sites, such as vial stoppers and intravenous solution ports, should be disinfected with sterile 70% isopropyl alcohol (IPA) and allowed to dry before they are accessed.
11. Ampoules and vials should be opened and accessed using appropriate aseptic techniques to minimize particulate contamination. Appropriate filtration should be used when withdrawing solutions from glass ampoules when required.
12. Reconstituted powders should be mixed carefully according to the manufacturer’s recommendations to ensure complete dissolution of the drug.
13. Needle entry into vials with rubber stoppers should be done at a 45-degree angle to minimize rubber core particulates.
14. All finished products should be carefully inspected after preparation for visible precipitation. This should be done outside the laminar air flow hood.
15. Each compounded sterile preparation (CSP) should be assigned an appropriate beyond-use date (BUD) in accordance with applicable USP <797> requirements and available stability and sterility information. The assigned BUD should reflect the preparation, compounding conditions, storage conditions, and other applicable requirements.

Conclusion

Sterile compounding requires appropriate facilities, equipment, procedures, and trained personnel operating in accordance with applicable sterile compounding standards and requirements. Not all community pharmacies may have the facilities or resources necessary to prepare compounded sterile preparations. Pharmacists should evaluate their facilities, equipment, personnel, and procedures before providing sterile compounding services. When appropriate engineering controls, aseptic techniques, policies, and procedures are properly implemented, they help reduce contamination risks and support the preparation of quality compounded sterile preparations for patients.