United States Pharmacopeia 800: Hazardous Drugs – Handling in Healthcare Settings
Section 5: Facilities and Engineering Controls
Sections 1 through 4 of United States Pharmacopeia (USP) Chapter 800: Hazardous Drugs—Handling in Healthcare Settings is the blueprint to our road to compliance. To date we have established the scope of our project, we know risk agents associated with our project, we have our crew and a supervisor assigned to help us meet our timeline.
Section 5 of USP 800 introduces the team to the more non-traditional handling aspects associated within the facilities for consideration where hazardous drugs (HDs) are handled. Formally designated areas where HDs are handled must have signage alerting folks to the hazards that lay within. Designated areas must include receiving/unpacking, storage locations, non-sterile HD compounding, and sterile compounding. These locations must be located away from non-trained staff and the public to reduce the risk of exposure. Some of these areas where HDs are handled may need to be negative pressure in relation to adjacent spaces. The negative pressure helps to keep any residue, spills, and vapors from being disseminated out to other locations. Based on the importance of the ventilation system for this aspect of safety, sites should consider placing this system on emergency power.
Facilities and Engineering Controls for Receiving HDs
The standard states “antineoplastic HDs and all HD APIs must be unpacked (i.e., removal from external shipping containers) in an area that is neutral/normal or negative pressure relative to the surrounding areas.” However, due to the lack of consistent a warning symbol for HDs in the United States, packaging practices by wholesalers and shipping companies are inconsistent with the labeling of totes and boxes with warning labels. Some of these companies may place the most common injectable antineoplastics in Ziploc Baggies and label totes accordingly, however, this should not be relied upon. Due to the concern of breakage, totes and boxes should not be opened in sterile compounding locations or in positive pressure rated rooms. Sites can create a ‘Department HD’ and order all of the HDs on this department account. By doing this, totes will be labeled ‘Department HD,’ thus allowing sites to better control the identification of totes with HDs.
Facilities and Engineering Controls for Storage HDs
Storage considerations outside temperature, humidity and light exposure for HDs should also include a system that prevents spilling and or breakage if the vials fall onto the floor. Bins used for storage should be easy to clean with a high surrounding lip to encompass the entire stock of vials. Over crowding of bins and using bins with a lower front lip may lead to vials falling out. Over crowding of bins can also lead to vials falling behind the bins and also falling into other bins, possibly leading to errors in pulling medications.
Antineoplastics and any other HDs requiring any type of compounding, other than repackaging, must be stored in designated areas away from non-HDs to prevent cross-contamination, in a negative pressure room, and 12 air changes per hour (ACPH). Non-antineoplastics and reproductive risk products in their final dosage form may be stored with non-HDs drugs but should be clearly labeled as hazardous to alert staff.
Antineoplastics requiring refrigeration must be stored in a dedicated refrigerator in a room with at least 12 ACPH with negative pressure and a room exhaust vent located adjacent to the coils or compressor.
Facilities and Engineering Controls for Compounding
When designing the HD compounding practice, emphasis on minimizing cross-contamination between products should be a priority. USP 800 introduces us to three levels of engineering controls: Containment-Primary Engineering Controls (C-PEC; A.K.A. hood); Containment-Secondary Engineering Controls (C-SEC; A.K.A. room) and Supplemental Engineering Controls such as Closed System Transfer Devices (CSTDs). Compounding sterile and non-sterile HDs must be conducted in a C-PEC located within a C-SEC.
The C-PEC for sterile HDs must be externally vented through a HEPA to the outside; in a separate room that is negative pressure of -0.01 to -0.03-inch water column to the adjacent room(s) with adequate ACPH. The C-PEC must run continuously and emergency power should be considered. If the C-PEC is turned off or moved, it must be properly cleaned and purged according to the manufactures recommendations prior to compounding.
A sink and eyewash station must readily available. Water and drains must be more than 1 meter from the C-PEC and it is highly recommended that all water sources not be located in buffer rooms.
Sites that choose to use the same C-SEC (room) for both sterile and non-sterile compounding can do so as long as the C-PEC’s (hoods) are located more than 1 meter apart and powder generating compounding does not occur at the same time that sterile compounding takes place.
Facilities and Engineering Controls for Non-Sterile Compounding
Hazardous Drugs, excluding the antineoplastic HDs, not requiring any physical manipulation activities such as counting and repackaging do not require the use of C-PEC. Manipulation activities such as splitting tablets, opening capsules, crushing doses do require the use of C-PEC such as a Biological Safety Cabinet (BSC) Type I or type II A2 or Type II B2; Compounding Aseptic Containment Isolator (CACI), or, Containment Ventilated Enclosure (CVA). The C-PEC must be located in a separate room with 12 ACPH, negative pressure of -0.01 to -0.03-inch water column to the adjacent room(s). If a BSC or CACI is used for both sterile and non-sterile compounding; it must be properly cleaned between doses.
For the C-SEC (rooms) the same requirements laid out for USP 797 for surfaces, ceilings, walls, doors, fixtures, flooring must be non-porous and easy to clean.
Facilities and Engineering Controls for Sterile Compounding
In addition to the foundation of USP 797, the C-PEC used for sterile compounding must be externally vented and a laminar airflow workbench must NEVER be used to compounding HDs. The C-PECs for sterile HD compounding can be either a BSC Type II A2 (recycles part of air through HEPA filter onto the workspace); or BSC Type II B2 (100% of air vented to the outside); or, a CACI. The C-SEC must be negative pressure versus the positive pressure standard for non-HD compounded sterile products.
In USP 800, a new option for the Containment-Segregated Compounding Area (C-SCA) differs in that this C-SEC room is not fed HEPA air, is not rated to ISO-7 and has only12 ACPH. However, the C-SCA must still be externally vented and negative pressure to adjacent space(s) by at least -0.01 to -0.03 inches of water column. If a site chooses to have a C-SCA, they are NOT allowed to use standard USP 797 BUDs for Low-and Medium- risk products. They use the dating seen in a segregating compounding area(s), BUD 12 hours or less.
For those sites wanting to use the maximal BUDs of USP 797, the C-SEC must have HEPA filtered, ISO-7 air quality or better, 30 ACPH and negative pressure to the adjacent spaces. The movement of products into and out of the rated spaces should be mapped out to minimize the potential for contamination. The use of a pass through and Ziploc Baggies will assist with the transfer. The use of pass through refrigerators are not recommended due to the quality of the air within the refrigerators and do not match the rated rooms spaces.
Containment Supplemental Engineering Controls
Although not a hood or a specially designed room, containment supplemental engineering controls are devices designed SPECIFICALLY for safe compounding and safe administration of hazardous drugs. The primary devices within this class include the Closed-System-Transfer-Devices (CSTDs). CSTDs have been on the US market since 1999, however, the overall adoption rate of these devices for facilities in the US for compounding HDs is around 50%. In place of using a CSTD, sites still opt to use a needle and syringe for the compounding process. The key term of CSTD is the word ‘Closed.’ From mounting the vial, until the disposal of the dose after administration to the patient, the system is closed to the healthcare providers and the environment. It is important to note that a CSTD must be used in conjunction with a C-PEC located within a C-SEC or C-SCA. To date, there are 7 approved CSTDs on the US market and each is cleared by the FDA as CSTDs. However, each CSTD is very different and sites are left to look at each of the devices to see which best fits their practice site. Visante consultants have a considerable amount of experience with CSTDs and are available to assist sites with the CSTD selection process.
Currently, USP 800 recommends the use of CSTD during compounding and mandates the use of the CSTD for drug administration. Best practice is for sites to implement the use of a CSTD for both compounding and drug administration.
As the official implementation date of July 1, 2018, for USP Chapter 800 Hazardous Drugs—Handling in Healthcare Settings compliance is rapidly approaching, the time for review of USP’s newest chapter is now rather than June 30, 2018.
Don’t know where to start with a hazardous drug safety program? Visante offers a full line of consulting activities to clients just starting down the road to compliance to practice sites on the journey and wanting to go beyond minimal practice standards. Contact Fred Massoomi, Pharm.D., FASHP at firstname.lastname@example.org.
 USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings
http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings. Accessed July 18, 2017
 NIOSH . NIOSH alert: preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165. http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf Accessed July 18, 2017.