Life Sciences - USP 797: A work in progress
By Hank Rahe, Containment Technologies Group
USP 797 was introduced in January 2004 as an enforceable regulation, and the document was a surprise to many involved in the compounding of sterile preparations. General chapter <797> Pharmaceutical Compounding-Sterile Preparations addresses the compounding of sterile products in any setting, including healthcare institutions, pharmacies, physician practices and other facilities in which sterile preparations are compounded. The intent of the document is to provide the practitioner with procedures, requirements and expectations for facilities, personnel training, documentation and maintenance. It is intended to provide guidance for sterilization of compounded preparations in terms of methods, equipment and facilities. The document is supported by a number of other USP general chapters, some of which are enforceable by law and some are for information only.
The United States Pharmacopeia (USP) is a nonprofit organization that has been granted the right to establish quality standards for materials and methods for the purpose of promoting the public health. USP 797 falls under the general chapters section of the publication, which has two types of chapters: Chapters with numbers over 1000 are considered informational and those with numbers under 1000 are recognized as enforceable by law.
The Council of Experts is the standards-setting body of USP. It consists of 62 expert committee chairs who are elected to five-year terms, with the current councils having been elected in April 2005. The election committee consists of the chair of the council, convention president and the vice chair of the nominating committee. After the chair of the committee is elected, he or she proposes committee members. The proposed committee members are then chosen for the committee.
Public stakeholders, or the public in general, are involved in the process by submitting proposals for changes to USP 797. The process for submitting proposed revisions is outlined on the USP Web site and allows individuals, manufacturers and those regulating the activity to provide input for consideration by the expert committee.
The successful compounding of sterile products requires a number of things to come together in order to provide the end user with a safe preparation; the facilities, personnel and methods employed must all be compliant with best practices as well as existing regulations. The initial version of USP 797 in 2004 recognized a wide difference in compounding activities, which can be defined by type and level of risk associated with the manipulations required to compound a preparation. Low-, medium- and high-risk levels were established to separate these activities according to the potential probability of contamination of the compounded preparation. The high-risk category describes activities and ingredients having the greatest risk. Each risk level includes a description of conditions, examples of compounding practices, and quality assurance measures that should be implemented in order to successfully compound a preparation that falls into a particular risk category.
The document reflects the authors in terms of their individual expertise within the council of experts. USP 797 has basic errors and omissions that have not been corrected to date. These information gaps may reflect the make-up of the council, which is composed of well-respected individuals in the profession of pharmacy but not experts in engineering, aseptic processing and quality management.
The technical support staff for compounding facilities, such as engineering, aseptic processing and quality systems, is generally much less common in compounding facilities than in parenteral manufacturing environments. The identification of engineering terms and practices for the preparation of sterile products requires not only knowledge of mechanical systems and equipment but also input from individuals well-versed in decontamination practices.
A lack of experience in these areas is reflected in the terms used in the explanation and description of ISO air quality requirements. ISO standards are cited for defining cleanroom and critical-site exposure environments. The ISO standards are described in the USP document using terms such as “ISO Class 5.” This description leaves a void in terms of what particle size and under what conditions the environment is to be tested for compliance as required by ISO. Without this additional information, it is left to individuals to interpret the intent of the committee.
Selecting the particle size for testing is a relatively simple choice with the information already in FDA documents. Selecting the conditions under which the testing is to take place is simple for static or built conditions. However, if dynamic testing were to be required, then the dynamic conditions must be defined. If standardized testing conditions are to be used, the pharmacy community must create definitions that specifically describe the testing conditions.
To help support the efforts of the expert committee to correct errors and improve USP 797, it would be helpful for the contamination-control community to read the document and contribute their expertise to clarify and improve the document. Comments and suggested corrections to USP 797 can be addressed to Claudia Okeke at USP (e-mail: email@example.com).
Upcoming issues of CleanRooms magazine will contain articles addressing the individual sections of USP 797. In these articles, experts in the area of facilities, contamination control, documentation, testing and aseptic processing will express their opinions on the document. You, the readers of CleanRooms, can also provide input on each of the critical areas that comprise USP 797. This will help to improve and clarify the document and will benefit the practice of compounding sterile preparations and, ultimately, patient safety. III
Hank Rahe is director of technology for Containment Technologies Group and is a member of the CleanRooms Editorial Advisory Board. He can be contacted at firstname.lastname@example.org.