USP <797> vs. Turbulent (nonunidirectional flow) Isolators 

Date:  May 23, 2008

The views expressed herein are the personal views of Air Safe, LLC. and not necessarily those of the compounding pharmacy industry, isolator manufacturer’s or those of any other individual or entity.

I am sure you are aware the revised USP <797> becomes effective on June 1st this year.  The revised document has some specific details concerning the usage of compounding isolators I feel obligated to inform you about.  We have also collected field data on a number of different isolators located in many hospital pharmacies and will share that data with you as well.

First let me state the section of the USP <797> which may be of concern to you and then my professional response.

HAZARDOUS DRUG MANIPULATIONS

Excerpt from page 14 of <797>

The ISO Class 5 (see Table 1) BSC or CACI shall be placed in an ISO Class 7 (see Table 1) area that is physically separated (i.e., a different area from other preparation areas) and optimally has not less than 0.01-inch water column negative pressure to adjacent positive pressure ISO Class 7 (see Table 1) or better ante-areas, thus providing inward airflow to contain any airborne drug. A pressure indicator shall be installed that can be readily monitored for correct room pressurization. The BSC and CACI optimally should be 100% vented to the outside air through HEPA filtration.

If a CACI that meets the requirements of this chapter is used outside of a buffer area, the compounding area shall maintain a minimum negative pressure of 0.01-inch water column and have a minimum of 12 ACPHs.

When closed-system vial-transfer devices (CSTDs) (i.e., vial-transfer systems that allow no venting or exposure of hazardous substance to the environment) are used, they shall be used within the ISO Class 5 (see Table 1) environment of a BSC or CACI. In facilities that prepare a low volume of hazardous drugs, the use of two tiers of containment

(e.g., CSTD within a BSC or CACI that is located in a non-negative pressure room) is acceptable.

My condensed interpretation is:  If you use a containment isolator and it meets the USP requirements and you only perform low volumes of hazardous drugs you can utilize the isolator in an area without the negative pressure requirement; however the 12 air changes per hour still apply.  If this is not your situation, you should look into installing environmental controls to comply with the above excerpt.

HAZARDOUS DRUG STORAGE

Excerpt from pages 13-14 of <797>

Many hazardous drugs have sufficient vapor pressures that allow volatilization at room temperature; thus storage is preferably within a containment area such as a negative pressure room. The storage area should have sufficient general exhaust ventilation, at least 12 air changes per hour (ACPH)4 to dilute and remove any airborne contaminants.

My interpretation is:  Hazardous drugs may be stored in your negative pressure chemo room with your isolator or BSC.  You must have a minimum of 12 ACH, so your drug storage area(s) should be monitored for air change rates.

AIR FLOW REQUIREMENTS FOR THE CRITICAL AREAS (ISO CLASS 5)

Excerpt from page 21 of <797>

HEPA-filtered air shall be supplied in critical areas (ISO Class 5, see Table 1) at a velocity sufficient to sweep particles away from the compounding area and maintain unidirectional airflow during operations. Proper design and control prevents turbulence and stagnant air in the critical area. In situ air pattern analysis via smoke studies shall be conducted at the critical area to demonstrate unidirectional airflow and sweeping action over and away from the product under dynamic conditions.

My interpretation is:  If you use a compounding isolator it must utilize uni-directional airflow within the critical area.  Turbulent airflow within the critical areas is not acceptable concerning the requirements of the USP <797>.

You can determine if your isolator is a turbulent flow unit or a unidirectional unit by calling the manufacturer, us or by looking at the supply HEPA filter set up within the critical area of the isolator.

PLACEMENT OF COMPOUNDING ISOLATORS

Excerpt from pages 21-22 of <797>

CAIs and CACIs shall be placed in an ISO Class 7 (see Table 1) buffer area unless they meet all of the following conditions:

•           The isolator shall provide isolation from the room and maintain ISO Class 5 (see Table 1) during dynamic operating conditions, including transferring ingredients, components, and devices into and out of the isolator and during preparation of CSPs.

•           Particle counts sampled approximately 6 to 12 inches upstream of the critical exposure site shall maintain ISO Class 5 (see Table 1) levels during compounding operations.

•           Not more than 3520 particles (0.5 um and larger) per m3 shall be counted during material transfer, with the particle counter probe located as near to the transfer door as possible without obstructing the transfer.8

Our field testing data supports that isolators located outside of a buffer area (ISO Class 7) which utilized unidirectional flow for the critical areas meet these requirements.  Isolators we have tested which utilize turbulent flow in the critical areas have been problematic at best in meeting these requirements.

RECOVERY TIMES FOR ISOLATORS

Excerpt from page 23 of <797>

When isolators are used for sterile compounding, the recovery time to achieve ISO Class 5 (see Table 1) air quality shall be documented and internal procedures developed to ensure that adequate recovery time is allowed after material transfer before and during compounding operations.

Our field testing data show that isolators which utilize unidirectional airflow in the critical areas recover from a simulated breach† typically in less than one minute and we have yet to see one not recover within three minutes.

Our field testing on turbulent flow isolators show dramatically different results.  In most cases the turbulent flow isolator does not recovery to an ISO class 5 environment even after 30 minutes.  In many field tests we have stopped the recovery test due to time constraints and after 15 minutes we are still measuring over 28,000 particles per cubic meter.  (An ISO Class 5 requires no more than 3,520 particles per cubic meter.)

Based on our field testing of the recovery periods for various isolators we recommend no less than a one hour wait (purge) time after any material transfer into or out of an isolator which utilizes turbulent flow in its critical space.

†  This test is performed in accordance with the CETA Compounding Isolator Testing Guide:  CAG-002-2006; section 2.07.

VIABLE SAMPLING

Excerpt from page 25 of <797>

Air sampling shall be performed at least semiannually i.e., every 6 months) as part of the re-certification of facilities and equipment. If compounding occurs in multiple locations within an institution (e.g., main pharmacy, satellites), environmental sampling is required for each individual compounding area.

You should be performing viable sampling in all critical areas (hood/isolators) and the buffer rooms.  Active air sampling is required, settling plates are not sufficient.  We can provide this sampling and reporting for you if you are not already doing this in house.

I hope this information is helpful to you in verifying your compliance with the USP <797> document.  If you should have any questions, please do not hesitate to give me a call anytime.

Sincerely,

Michael D. Alleman

President

Air Safe, LLC.

888-924-7723