The Compounding Expert Committee of the US Pharmacopeial Convention decided to propose some changes and revisions to the existing USP General Chapter 797 Pharmaceutical Compounding – Sterile Preparations.
These revisions differ from the existing chapter in some significant ways – both structure and content. These changes, at least some of them, will undoubtedly require the pharmacy system and processes to undergo some significant adjustments. Although, many of the variations will be easier to implement.
The changes are set to become official and take effect on December 1, 2019. Public comments on these changes are no longer heard, but we can still take a look at some of the most significant changes that will take effect in less than a year.
Changes to the Classification of CSPs
CSP (Compounded Sterile Preparation) classification has witnessed a significant overhaul with these proposed changes.
The current system classifies CSP as either low, medium, or high risk. The rankings are based on the number and types of manipulations in the compounding, and the sterility of the starting ingredients.
In the new system, on the other hand, the classification is entirely different. The three risk system is eliminated, and a new classification system introduced. Sterile preparations are now placed in only two classes – category 1 or 2. The categories are based on the conditions in which the products are prepared.
Category 1 CSPs are sterile preparations made in a segregated compounding area. The area consists of a single ISO 5 primary engineering control (like a laminar airflow workbench) which is always located just outside of an ISO 7 clean room.
Category 2 CSPs are sterile preparations also made in an ISO 5 primary engineering control, but this time – it has to be located inside of a clean room environment.
Changes to the Beyond-Use Dating System
The requirements for beyond-use dating and the entire system for allocating these dates to CSPs has also undergone through some changes.
Until now, the dates were assigned based on the risk level of preparation, and it was always a maximum allowable date (BUD – beyond-use date).
The change which will implement soon complicates the system to ensure the safety of products. This new system for allocating BUDs is based on a couple of different factors, all of which are related to either maintaining existing sterility or achieving it.
The new system:
Category 1 CSPs can only get a BUD of 12 hours in controlled room temperatures or 24 hours in refrigerated conditions.
Category 2 CSPs have a more complicated and varied system of requirements for assigning BUDs. It is especially true for CSPs which are:
- Terminally sterilized
- Tested for sterility
- Prepared with sterile components only
- Stored in refrigerated or in frozen conditions
Aseptically prepared CSPs to have BUDs which range from a single day to 60 days, based on whether or not they passed sterility testing and on the temperature they are stored in. The more sterile they are and the colder the storage conditions, the higher the BUD.
Terminally sterilized CSPs receive BUDs also based on the same requirements. However, the numbers are now higher, and they range from 14 to 90 days.
When it comes to terminally sterilized CSPs, there are some additional changes outside of the BUD system. First of all, these CSPs have longer BUDs because they are sanitized in final container-closure systems and sterilized with the use of filtration. Furthermore, terminal sterilization means dry heat, irradiation, and steam, for example. This type of sterilization is also the preferred method, and the current existing chapter already supports this. However, the changes require the CSP or the container-closure system to tolerate terminal sterilization for this method to be the preferred one.
Changes in the Requirement for Conducting Investigations and Implementing Corrective Actions
The most important thing to note about these changes is that much greater emphasis has been placed on these requirements.
The existing version of the chapter only requires an investigation to be started in the event of:
- Sterility test failure
- Recovery of colony-forming units in environment monitoring, if the activity level of the facility has been exceeded
The changes, on the other hand, introduce a much larger number of such specific scenarios which necessitate investigations by a designated person or the implementation of corrective actions. These events include:
- Personnel qualification failure
- Facility certification failure
- Quality control check failure
- Media fill failure
- Complaints on quality of CSPs
- Out-of-specification results in laboratory tests
- Other adverse events
Changes in Requirement for Calibration, Qualification, and Certification
Once again, as the case was in the previous section, changes are made that place a greater emphasis on the need for routine calibrations, qualifications, and certifications for equipment and classified areas.
There are a lot of changes here, but for example, these changes explicitly state the need for continuous and regular certification or calibration of pressure and temperature monitoring devices and incubators. In addition to that, these changes require the use of calibrated chart recorders which monitor sterilization in autoclaves and dry heat ovens in each cycle.
Equipment is not the only area that requires checks in these proposed changes, classified clean room areas now also have additional requirements or better explanations of existing requirements.
In the end, the new changes decisively require testing in its entirety of every part of the facility certification to be performed in dynamic operating conditions. These imply that the operating conditions need to be normal and for the personnel to be present in these rooms.
Unfortunately, we cannot provide you with a summary of all the changes in the USP chapter 797. There are too many of them to list in one article, no matter how long. You will have to review the changed document yourself to see how these changes will affect your practices. We strongly recommend that you do so, as the changes are essential and sometimes completely alter existing methods. You can take a more detailed look at the proposed revisions here.