Originally published by our sister publication Specialty Pharmacy Continuum

NATIONAL HARBOR, Md.—One of the major changes in the revised USP General Chapter <797> on sterile compounding is the move from categorizing compounded sterile preparations (CSPs) as low, medium or high risk to numbered categories of 1, 2 and 3. 

At the NHIA/DC 23 in National Harbor, Md., on March 26, 2023, USP senior scientist for the Compounding Expert Committee Selma Mitiche, PharmD, explained the rationale for this move and why it’s important, along with other key questions in the chapter revisions.

“When we labeled a CSP as high, medium or low risk, that assigns a risk level without considering all of the factors that influence quality,” Dr. Mitiche said. “A low-risk CSP made by poorly trained staff actually poses a very real and high risk, for example. So, we made the decision to move to numbered categories based on the conditions in which the CSPs are made and specific processes and preparation steps involved.”

Category 1 CSPs: Must be prepared in a primary engineering control (PEC) that may be located in an unclassified segregated compounding area, and are assigned a beyond-use date (BUD) of 12 hours or less at controlled room temperature or 24 hours or less when refrigerated. ?

Category 2 CSPs: Must be prepared in a cleanroom suite, and may be assigned a BUD of more than 12 hours at controlled room temperature or more than 24 hours if refrigerated.

Category 3 CSPs: Have additional requirements beyond preparation in a cleanroom suite that must be met at all times, and may be assigned a BUD longer than established for category 2 CSPs, up to 180 days. ?
“The bulk of CSPs will fall into category 2, for preparation in a typical cleanroom suite,” she said.

Stakeholder feedback on this topic was widely polarized, Dr. Mitiche noted. “Some said that the only way to extend BUDs is to move to a GMP [good manufacturing practices] environment like a 503B, while others said, ‘I went to school for a very long time; let me use my professional judgment to extend BUDs.’ The committee chose extensions of BUDs, but with limits that are stratified based on risk elements including the compounding process, the environment and storage conditions.”

The chapter has flexibility built in wherever possible, she said. “For example, the alternative technologies clause allows you to use technologies, methods and techniques not mentioned in the chapter, as long as they are noninferior and validated.”

Personnel training has been stratified based on the individual’s role. “The people who do the most have to be trained the most,” Dr. Mitiche said. There are three personnel categories:

• compounder or compounding oversight personnel,
• restocking, cleaning and disinfecting personnel, and 
• other personnel.

Compounders and those with compounding oversight must undergo training every 12 months in core skills. These include hand hygiene and garbing; cleaning and disinfection; calculations, measuring and mixing; aseptic technique; achieving and maintaining sterility; use of equipment; documentation of the compounding process, including Master Formulation Records and Compounding Records; principles of HEPA-filtered airflow; and principles of movement of materials and personnel within the compounding area.

This group of personnel must also complete aseptic garbing competency—every six months for those who compound CSPs categories 1 and 2, every three months for category 3, and every 12 months for those who have oversight but do not compound. “You have to pass garbing competency three times in a row,” Dr. Mitiche said. “They do not all have to be on the same day, but you can’t pass one, fail one, then pass two.”

She pointed out that the revised chapter includes increased flexibility in the garbing procedure. “The responsibility now falls on the facility or entity to develop SOPs [standard operating procedures] on the order of garbing, but it must be in an order that reduces contamination, and donning and doffing should not occur in the anteroom or sterile compounding area [SCA] at the same time.”

Finally, they must also successfully complete aseptic manipulation assessment, including media fill testing, on the same schedule.

“Because the point of media fill testing is to verify the skill of your personnel to prepare CSPs without contamination, it makes sense to test your most difficult and challenging procedures,” Dr. Mitiche said. “This would include factors associated with the length of the process that can pose contamination risk, such as operator fatigue and quality of equipment; number of aseptic additions or transfers; number, type and complexity of manipulations; and the number of personnel in the buffer room or SCA.”

Category 3 CSPs have additional personnel qualification requirements for garbing, gloved fingertip and thumb sampling, and media fill testing. As examples, no exposed skin is permitted, all low-lint outer garb must be sterile, disposable garbing items must not be reused, and laundered garb must not be reused without being laundered or resterilized with a validated cycle. “We can’t entirely eliminate risk, but we can have layers,” Dr. Mitiche said.

For non-compounding and oversight personnel, requirements are:
• Restocking, cleaning and disinfecting staff must meet requirements for personal hygiene and garbing, and undergo training and competency in the quality of the environment as well as ongoing training per the institution’s SOPs.
• “Other” personnel—such as outside cleaners, inspectors and anyone else who may have a need to enter your compounding facility—must comply with personal hygiene and garbing requirements and go through ongoing training per your SOPs.

“The reason that we have these standards goes beyond ensuring that this specific CSP is safe for this patient,” Dr. Mitiche said. “They build trust. The standards we develop, the quality we implement, are all about making sure that when patients have to make a decision about their care, they can trust the healthcare system.”