It’s Here! The Revision to CAG-009

Over the last two years, I have had the privilege of working with an outstanding group of CETA members who worked diligently to revise CETA Application Guide (CAG)-009. Expertise came from sterile compounding pharmacists, certification professionals, and microbiologists. It was with their dedication and the supportive guidance of the CAG committee, that we were able to draft a guide that meets the needs of sterile compounding industry professionals, not only for today but also for the future. Here are some highlights of the major changes to CAG-009.

How It’s Written

With the release of USP Chapter <825> Radiopharmaceuticals – Preparation, Compounding, Dispensing, and Repackaging, CAG-009 was written to meet the needs of this chapter and USP Chapter <797> Pharmaceutical Compounding – Sterile Preparations. Keeping in mind we were drafting a guide and not a standard, we did not repeat information that could be found in the USP chapters but instead provided guidance where USP <797> and <825> was lacking and included rationale for best practice recommendations. We made every effort to ensure the guide did not conflict with the 2008 or the 2019 versions of the chapters.

Title, Audience, and Scope

There are significant changes to the title, target audience, and the scope. The 2012 version was titled “USP <797> Viable Environmental Sampling & Gowning Evaluation.” The now current version is titled “Viable Environmental Monitoring for Sterile Compounding Facilities.” This change is due to the change in scope. The scope of CAG-009 now only covers viable air and surface sampling, specific to the needs of sterile compounding organizations. Initial and subsequent gloved fingertip sampling will be covered in a new guide, CAG-011, which has been drafted and is currently under review. The 2012 version of CAG-009 was really written more for the certifier, although it was also intended to provide guidance for compounders and facility managers. The revision is written with more general language and targets all sterile compounding industry professionals.

Media and Incubations Considerations

The guide addresses the types of media needed and addresses what you should look for when choosing media, such as the media being sterile, double bagged. Detail was provided on media storage and use, as there is still much confusion on whether media can be used to sample on its expiration date. As our research confirmed, for many media manufacturers, media may be used for the collection of viable air and surface samples up to and including the expiration date. Although, it is still necessary to ensure that this applies to the media chosen for use and the manufacturer’s instructions must be referenced. 

Significant detail was added to describe the single plate and dual plate incubation methods, especially since the 2019 version of USP <797> dictates very different indication parameters from the 2008 version of the chapter. The following was added as a best practice incubation recommendation:

• Single Plate Method: Incubate samples in an incubator, inverted at 30˚C to 35˚C for 48 hours to 72 hours and then incubate at 20˚C to 25˚C for 5 to 7 days.
• Dual Plate Method: Incubate TSA samples, in an incubator inverted at 30˚C to 35˚C for 48 hours to 72 hours. Incubate the other sample plates (TSA or fungal media) inverted at 20˚C to 25˚C for 5 to 7 days.

Notice the range on the incubation times. USP <797> (2019) did not have ranges and indicated that incubation had to be “at least” 48 hour or at least 5 days. This could result in samples being incubated to the point of desiccation, and any recovered growth may no longer be viable to perform identifications.

Sampling Standard Operating Procedure (SOP) and Plan

One area where both certification and sterile compounding professionals struggle is with the development of a sampling SOP and a robust sampling plan. The revision to CAG-009 discusses the need to perform a risk assessment when choosing sample locations, as this will identify the locations that would cause the greatest risk to the sterility of the sterile compounded preparation. This section also provides guidance on some why certain locations should be included in a sampling plan.

Sample Analysis and Data Expression

The sample analysis and data expression for the single plate method is essentially the same as it was. One sample is collected at a location, it is incubated at two temperatures for the designated amount of time and all colonies recovered are counted and reported. The new guide provides greater detail for the analysis and reporting for the dual plate method. In this case, the total number of colonies recovered on both samples are counted and documented. In doing so all recovered colonies are reported, as opposed to the 2012 version of CAG-009 which stated that only the bacteria on the plate incubated at 30 to 35 °C and only the fungi on the plate incubated at 26 to 30 °C were reported. In analyzing the dual plate samples in this manner, it is now essential that each plate is reported separately, and that the total number of colony forming units recovered are each compared against the action level. 

Identification of recovered microorganisms is also addressed. Since we are between USP chapters right now, it was necessary to direct the reader to reference the current versions of applicable USP compounding chapters for identification requirements. However, the benefits of identification, beyond the minimum chapter requirements were also discussed.

Documentation

All the information that must be captured as part of the sampling, laboratory submission, incubation, analysis, and reporting was added to the section titled “Documentation.” This was done to give the reader a comprehensive list of everything that would have to be documented and be accessible. This information could be on a sampling form, chain of custody, or on the final report.

Investigation and Remediation

Ever since viable sampling was added to the USP Chapter <797>, certification and sterile compounding professionals have been struggling with what needs to be done in the event of an exceeded action level of the recovery of a “highly pathogenic organism.” An entire section was added to provide guidance on what need to be done in the event of an exceeded action level. Additionally, a table was created to provide pharmacy guidance on who to speak with and what to evaluate as part of their excursion investigation. This could also be used by the certification professional as they assist their pharmacy clients through an investigation.

Final Thoughts

On behalf of the CAG-009 Action Committee, we hope you find this guide to be a valuable resource. Although it was a long process, being a part revising CAG-009 was incredibly rewarding. I would like to personally thank the members for their hard work and dedication.

Jeremy Mahurin

Martin Burke

Ronald Dewalt

Jared Eberly

Sharon Danko

Anthony Grilli

Kyle Mulder

Denise Rodriguez

We look forward to bringing you CAG-011 on gloved fingertip testing and CAG-013 on media-fill testing!