The revised USP Chapter <797> in review
By Eric S. Kastango, RPh, FASHP, Clinical IQ
The wait is over! After 30 months since the 2005???2010 Sterile Compounding Expert Committee convened, the revised USP Chapter <797> is now available on USP’s web site (www.usp.org/USPNF/pf/generalChapter797.html). It is scheduled to become official on June 1, 2008, as a revised bulletin. While minor tweaks may be made to grammar and sentence structure, no changes to the content or substance of the chapter are anticipated in the near term. Although compliance with USP <797> has never been avoidable per se, it is now more important than ever.
USP <797> has been in effect since Jan. 1, 2004. Few states had embraced the chapter as their template for regulating compounding practice. With the revised chapter soon to be in effect, several states have signaled their expectation that compliance is no longer optional. There are several state boards of pharmacy (e.g., Nebraska, Pennsylvania, and New York) that still have no laws and regulations for sterile compounding. However, regardless of state laws, our obligation should be driven by patient safety first and foremost. This chapter applies to all practitioners who store, transport, or prepare compounded sterile preparations (CSPs).
The chapter has been through an extensive revision process and has been reviewed by several expert groups. It is a synthesis of evidence-based science and best practices from the contamination and infection control industries and supports health care providers with a set of minimum practice and quality standards when delivering CSPs. This column outlines some of the most significant areas of changes within the revised USP <797>; however, there is no substitute for a thorough reading of the chapter. As health care professionals, we are obligated to familiarize ourselves with primary source material instead of relying solely on the interpretations offered by secondary sources.
Allergen extracts as CSPs
One of the first significant areas of change within the updated chapter is its recognition of, and quantified requirements for, patient-specific allergen extract CSPs. This section was developed with extensive input from AAOA/JCAAI (American Academy of Otolaryngic Allergy/Joint Council of Allergy, Asthma and Immunology) and other allergen compounding experts, in addition to the results of a peer-reviewed research study of 292 patients who received 26,795 injections (>98.5 injections per person) that showed they had zero infections.
Hazardous drugs as CSPs
This revision incorporates recommendations from the NIOSH Alert. To protect operators from exposure to hazardous drugs and provide asepsis, personnel are required to work in an appropriate ISO 5 (Class 100) primary engineering control: a biological safety cabinet (BSC) or compounding aseptic containment isolator (CACI). CACIs must be placed in a negative-pressure room when not in an ISO 7 (Class 10,000) area. In addition, hazardous drugs must be stored separately from other inventory in a negative-pressure area.
In addition, the new chapter had added a provision for immediate-use preparations, recognizing that, in some cases, it is not reasonable or feasible to delay treatment so that pharmacists or other health care personnel can gown and make appropriate use of primary engineering controls. The bottom line is that the SCC recognized that treating patients expediently is as important as treating them safely. This immediate-use category applies only to non-hazardous drugs or diagnostic radiopharmaceuticals requiring only simple aseptic measuring and transferring for preparation.
The revised chapter also makes provisions for remote compounding locations and satellite pharmacies. The Low-Risk Level CSPs with 12-hour BUD sections provide specific guidance for the applicability of compounding within an ISO 5 (Class 100) primary engineering control within a segregated area. The segregated area is a new concept in the revised chapter and was included because of the comments and feedback from reviewers. This category applies only to low-risk, non-hazardous, radiopharmaceutical drugs compounded within an ISO 5 (Class 100) device in which compounding and administration starts within 12 hours of preparation.
Facility design and primary and secondary engineering controls
Overall, USP <797> now clearly articulates the requirements for physical plant design, outlining detailed requirements for air cleanliness, frequency of air exchanges, pressure differentials, and facility temperature. Unidirectional airflow must be provided by all primary engineering controls: CAIs, CACIs, BSCs, and laminar airflow workstations (LAFWs). This requirement is consistent with the 2004 FDA Aseptic Processing Guidance Document. Cleanrooms for non-hazardous and non-radioactive CSPs must be supplied with HEPA-filtered air that enters from the ceiling and may be returned via low, wall-mounted vents, which are efficient in the removal of airborne particulate contamination. Low wall returns should be well distributed throughout the room and, ideally, have adjustable louvers or dampers.
Unlike any other guidance document, the chapter recognized that primary engineering controls can contribute to the air cleanliness and the number of air exchanges within a controlled area. These devices can provide up to 15 air changes per hour (ACPH). The buffer area (ISO 7 [Class 10,000] area) shall have no less than 30 ACPH. The contribution from primary engineering controls makes the facility requirements in the revised USP chapter less expensive than the original chapter. CAIs and CACIs proven to isolate can be located in an unclassified area. If used in this manner, the primary engineering control must be tested to the guidelines outlined in the CETA Compounding Isolator Testing Guide (CAG-002-2006).
Good aseptic technique requires compounding personnel to understand the concept of first air—unidirectional HEPA-filtered air immediately off the face of the filter that is virtually free of particulate contaminants. The revisions to USP <797> require that all critical manipulations must be carried out in unobstructed first air in order to provide a particle-free direct compounding area. Deliberate and methodical personnel actions, component disinfection, and proper product-handling placement minimize the risk of microbial contamination.
Gowning and gloving
The chapter’s personnel gowning and gloving requirements are harmonized with the CDC’s Guideline for Hand Hygiene in Health-Care Settings along with other scientific articles. The SCC received a significant amount of feedback from world-renowned experts in the area of infection control, cleaning, and disinfection, and the section of the chapter related to personnel reflects their guidance. The revised chapter requires the use of sterile gloves, frequently disinfected with sterile 70 percent IPA, during compounding activities.
It is important to understand that using a CAI or CACI does not obviate the need for sterile gloves during compounding activities. Sterile gloves must be donned when compounding within an isolator. The manufacturers of CAIs and CACIs can determine how best to outfit their isolators with sterile gloves.
Historically, USP <797> called for a pharmaceutical manufacturing model of environmental monitoring, requiring routine air, surface, and fingertip sampling in various locations, but now the chapter follows more of an infection control model. Recognizing that people are the primary source of contamination of CSPs, surface and fingertip sampling are now tied to specific, employee-related events, such as initial training, media fill verification, and the ongoing annual or semi-annual training and certification of compounding personnel (depending on risk level). In concert with the required facility air sampling, the new environmental sampling requirements should allow pharmacists and technicians to demonstrate a state of control in critical compounding environments, provided those environments are properly designed, constructed, and certified as functioning properly.
The revised requirements for environmental monitoring include the following:
- Viable, volumetric air sampling must occur at least every six months. Gravimetric methods (i.e., the use of plates or paddles) are not permitted for air sampling.
- Personnel fingertip sampling must occur during initial training, as part of the media fill process, and as part of the personnel competency assessment that takes place annually for low- and medium-risk compounding operations, and semi-annually for high-risk compounding operations.
- Surface sampling via contact plates and swabs must occur periodically, at the end of the compounding day.
Personnel training and evaluation requirements
The training and competency assessment is a critical aspect of ensuring the quality and sterility of CSPs. There is a greater emphasis in the revised chapter on compounding personnel training and competency.
The current chapter does not dictate the curriculum for compounding training, but there are a number of available educational resources that can aid pharmacists in their efforts to train and assess the competency of their compounding staff. USP <797> does require that personnel complete annual (for low- and medium-risk compounding) or semi-annual (for high-risk compounding) didactic training, followed by a written test. Additionally, all personnel must undergo a visual skills assessment, using observational audit tools, and successfully complete aseptic media fill testing. The chapter provides sample observational competency assess-ment checklists.
“If it wasn’t documented, it didn’t happen.” First and foremost, pharmacists need to follow their state board of pharmacy regulations regarding the documentation of compounding activities. Some states provide very specific guidance in this area. Documentation provides the evidence that quality standards were adhered to throughout the compounding process.
As health care professionals, compounding pharmacists are obligated to “first, do no harm.” With this in mind, it should be our professional responsibility and moral obligation to adhere to the evidence-based and best practice requirements set forth in the revised USP Chapter <797>. The delivery of parenteral medications has evolved significantly in the past 20 to 30 years, and the standards have changed to reflect that. While some of the traditional compounding practices are still very appropriate, others need to evolve; it is necessary to advance our understanding of the science of compounding and embrace these changes in order to advance the delivery of safe health care services.
There is no substitute for understanding the requirements of the revised chapter directly from the primary source material—the revised USP Chapter <797> itself. In order to ensure that the efforts to comply with the revised chapter are not fleeting, it is important to understand the principles and rationale for them so they can be applied regardless of practice setting.
Eric S. Kastango, RPh, MBA, FASHP, is the president, CEO, and owner of Clinical IQ, LLC, a provider of customized process and educational strategies for the pharmaceutical, medical device, and health care industries. A member of USP’s Sterile Compounding Expert Committee, he has practiced in the field of both hospital and home care pharmacy since 1980.