In an effort to prevent harm through contamination, the U.S. Pharmacopeial Convention has been working on a series of proposed changes to USP Chapter 797.1 Pending approval, processes to compounded sterile preparations (CSPs) will be affected, including changes to injections, irrigation solutions for internal body cavities, ophthalmics and aqueous bronchial inhalations. The changes to USP 797 will apply to all individuals who prepare compounded sterile preparations, as well as those who work in these environments.
The Purpose of Change
The proposed changes to the chapter are to continue preventing harm through microbial contamination, excessive bacterial endotoxins and inappropriate quality of ingredients. Additionally, USP 797 will be updated to reduce risk associated with unintended physical and chemical contaminants, as well as variability in intended strength. Currently, USP 797 is enforceable by the U.S. Food and Drug Administration, as well as 28 State Boards of Pharmacy.
Proposed Major Changes to USP 797
There are a series of major changes being proposed to USP 797, including the rejection of the following statement from Section 503A of the Federal Food, Drug and Cosmetic Act:2
“Compounding does not include mixing, reconstituting, or similar acts that are performed in accordance with the directions contained in approved labeling provided by the product's manufacturer and other manufacturer directions consistent with that labeling.” The proposed revision of USP 797 advocates this is still compounding in spite of access to directions associated with proper labeling.
Additionally, a new Beyond-Use-Date (BUD) paradigm has been presented as a part of USP 797. The proposed rule states that the BUD can only be determined from the time that the CSP is compounded. Furthermore, the BUD cannot exceed 45 days, regardless of a sterility test being performed.
Here is a summary of other additional proposed changes to USP 797:
- Master formulation and compounding records will be required for all batch and non-sterile compounding activities.
- “In-Use Time” will be used to describe the time before which a manufactured product or compounded dilution bag must be utilized after it has been punctured.
- Sterile sleeves, in addition to sterile gloves, must be donned prior to compounding under certain conditions.
- Viable air and Surface sampling is required each month.
- A visual observation of hand hygiene and garbing must be conducted every quarter.
- USP 800 will be used to outline Hazardous Drug requirements and referenced in USP 797.
- Three risk levels have been changed to two categories, which are distinguished according to the conditions under which CSPs are made and time within which they are used.
CSP Categories Under USP 797
There are two categories of CSPs proposed under USP 797: “Category 1 CSPs” and “Category 2 CSPs.” Under the Category 1, endotoxin and sterility testing would not be required. The compounding environment also does not have to contain ISO classified air. Category 1 CSPs would have a BUD of 12 hours or less at room temperature and 24 hours or less when refrigerated. The BUD for Category 2 CSPs would be the same, and endotoxin testing would not be required for sterile components. However, sterility testing would be recommended based on the BUD, and the environment is required to have ISO classified air.
Personnel Training Under USP 797
Depending on whether the personnel is working with Category 1 or 2 CSPs, their garbing may vary. In all cases, non-cotton, low-lint disposable gowns should be worn. Head and facial hair should also be covered, and sterile sleeves and gloves must be used. However, Category 2 CSPs would require the use of a mask, unlike Category 1 CSPs. Eye shields would also be an option for personnel handling Category 2 CSPs.
A gloved fingertip test would be recommended each quarter under the new USP 797 guidelines, as opposed to semi-annually or annually. A media fill would also be required quarterly, instead of semiannually or annually. Furthermore, a failed test would require three successful repeats prior to restarting. At the present time, a failure constitutes requalification.
Under the proposed changes, a compounding area must be free of cracks and crevices. The buffer area around the compounding location must also be free of water sources, such as sinks or floor drains. Category 2 CSPs must have a positive pressure buffer room with access through a positive pressure anteroom. It also needs to be situated in an ISO Class 7 area,3 where garbing is worn by personnel. The room temperature in both Category 1 and 2 CSPs should be at 20 degrees or cooler with a relative humidity level of less than 60 percent. Furthermore, a CSP cannot be re-frozen after it has been thawed.
The Introduction of Urgent-Use CSPs
It is proposed that “Urgent-Use” will replace “Immediate-Use” in terms of specific CSPs that need to be utilized as soon as possible. The Urgent-Use guidelines state that a CSP can be prepared in conditions worse than ISO Class 5 air when it needs to be used for a single patient. Compounding procedures are not permitted to exceed one hour, and naseptic technique must be used during preparation.
Public responses to the proposed changes can be submitted by utilizing the Comment Submission Template, accessible on www.USP.org. Your comments will be accepted if they are sent to firstname.lastname@example.org by January 31, 2016.
- Kastango, Eric. “Proposed USP Chapter 797.” ClinicalIQ. September 25, 2015. <www.clinicaliq.com>
- “Section 503A of the Federal Food, Drug and Cosmetic Act.” FDA. Retrieved October 27, 2015. <www.fda.gov>
- “ISO Class 7 Cleanrooms.” Blue Thunder Technologies. Retrieved October 27, 2015. <www.bluethundertechnologies.com>