New & Improved!

The Upcoming USP <797> Revision
April 2016 - Vol. 13 No. 4 - Page #2

Q&A with Eric Kastango, MBA, RPh, FASHP
President and CEO of Clinical IQ, LLC, and CriticalPoint, LLC

Pharmacy Purchasing & Products: How will the changes to USP <797> impact pharmacy overall?

Eric Kastango: The USP Compounding Expert Committee published the proposed revisions to USP <797> on September 25, 2015 and the public comment period closed on January 31, 2016. Once the chapter is finalized, the changes likely will require more resources and focus devoted to quality assurance and control activities to ensure pharmacies are achieving and maintaining a proper state of control and can prove it. Knowledgeable staff will be needed to perform additional activities, such as more frequent personnel and environmental testing. Improved dedication to effective employee training and meaningful competency measurement will be required.

The practice of sterile compounding has been drawn into the spotlight in recent years, making it one of the featured parts of pharmacy operations. As such, many independent regulatory entities are looking at compounding in greater detail.

We know that the state boards of pharmacy are actively inspecting for USP compliance. Many state board inspectors have attended the CriticalPoint Sterile Compounding Boot Camp or the NABP Sterile Compounding Inspector Training (SCIT) program and all state boards of pharmacy have access to CriticalPoint’s Web-based sterile compounding curriculum. They are now well informed on how to inspect pharmacies. Additionally, CMS announced in October 2015 that their Conditions of Participation will require hospitals to comply with <797>, which, in turn, will impel all of the accreditation organizations also to inspect for compliance.

Based on the results of both the CriticalPoint USP <797> Compliance Survey and PP&Ps State of Pharmacy Compounding survey, significant opportunity exists for pharmacy to make improvements to their compliance efforts.

PP&P: How are the changes to the chapter likely to impact pharmacies that have already achieved <797> compliance?

Kastango: Given the anticipated increase in the frequency of environmental monitoring, organizations will have to consider bringing this responsibility back into the pharmacy. Currently, many hospital pharmacies subcontract viable air sampling to their certifiers who typically conduct this testing during the certification of the primary and secondary engineering controls. To meet the more frequent air sampling requirements, pharmacy should consider purchasing a volumetric air sampler and other equipment, such as an incubator, to effectively integrate these critical performance metrics into their workflow. The development of detailed training programs will be required to ensure proper implementation of these activities.

For those facilities that have yet to achieve <797> compliance, consider that compliance is not a destination; rather, it is a journey. Nonetheless, the current version of <797> has been in effect for 8 years; the journey must be undertaken in earnest. Many compliant work practices can be implemented at little cost, such as proper employee garbing, robust hand hygiene, and cleaning and disinfecting procedures. Non-compliant organizations put patients at risk; furthermore, pharmacists and technicians may be held legally accountable for any harm resulting from noncompliance.

PP&P: How can pharmacy work with risk management and administration to ensure proper funding and support to attain compliance?

Kastango: Pharmacy has a fairly easy story to tell relative to the risks of poor practice related to sterile compounding. Pharmacy executives and managers must take the time to explain the rationales behind compounding safety and detail the potential return on investment to those who hold the purse strings. This requires pharmacy to work collaboratively with the C-suite, risk management, legal, medicine, nursing, environmental services, and others. Proper funding will be forthcoming when all parties recognize how compliance benefits patients and staff; besides, compliance is not optional.

A key component of the message that should be communicated to leadership is: Quality costs! This is a simple fact, but by investing more money on needed compounding equipment, supplies, training, and technology, we have the opportunity to focus on recouping dollars by reducing compounding waste.

PP&P: What are some of the specific changes we can expect to see in the revised chapter?

Kastango: USP chapters are constantly being reevaluated. <797> has been under review since 2010 and has been significantly revised to clarify the requirements and reflect stakeholder feedback and learnings since the previous revision was released in 2008.

The chapter’s structure is modeled much like the FDA’s current good manufacturing practices (cGMPs), which had a significant influence on the development of the chapter revisions. Some of the major revisions involve changes to the placement of primary engineering controls, the frequency of environmental sampling, and the limitation on beyond-use dating to no more than 42 days if refrigerated and 45 days if frozen. I typically support shorter BUDs as there is rarely a good reason that compounded drugs made under <797> need more than a total of 59 days (14 days for sterility testing and 45 use by days) with the exception of medications for implantable pumps. However, many of the drugs used in these pumps have extended chemical stability and during the instillation of the drug into the pump, the practitioner uses a 0.22 micron filter and the pump has 0.22 micron filter integral to its drug delivery mechanism.

In order to use a BUD greater than 12 hours under room temperature and 24 hours if refrigerated, the primary engineering control—including compounding aseptic isolator (CAI) and the compounding aseptic containment isolator (CACI)—has to be located in a cleanroom suite with an ISO Class 7 anteroom and a separate ISO Class 7 buffer room. This will have a significant impact on hundreds of organizations. Be sure to note that in the revision the CAI and CACI are referred to as RABS (restricted access barrier systems).

There are some changes in the revised chapter that I find problematic. The revised chapter suggests switching from the three standard risk levels (ie, low-, medium-, and high-risk) to two neutral Categories 1 and 2. Since 2004, the lexicon of sterile compounding has used low-, mediumā€ and high-risk levels, so there is concern that confusion may result from changing the terminology. Across the industry, there is a general understanding of the differences between these levels and the compliance efforts for the last 12 years have been directed by this risk-based approach. The reality is that risk levels are not neutral categories. Risk is influenced by changes in the compounding environment, compounding ingredients, and compounding complexity, and those performing the compounding need to be mindful of this. The differences between risk levels need to be further refined so they are easier to understand and determine what comprises low-risk vs medium-risk (eg, single doses vs batched doses). The FDA Guidance for Industry Q9, Quality Risk Management states: “It is commonly understood that risk is defined as the combination of the probability of occurrence of harm and the severity of that harm.” The neutral categories are primarily differentiated by the air cleanliness of the environment and the beyond-use dating assigned. This does not take into consideration core values that the FDA expects from manufacturers regarding risk; as such, I do not endorse this change.

Risk levels are used to establish the appropriate facility design, personnel qualification levels, media fill frequencies, environmental monitoring frequencies with appropriate responses to action level excursions, and setting beyond-use dating based on patient risk. The literature demonstrates there is more potential for actual harm when conducting high-risk compounding vs low-risk compounding. Additionally, route of administration and the antimicrobial nature of the drug should be factored into the BUD decision algorithm. Consider, for example, that topical ophthalmic eye products in a multiple-dose container for a single patient poses a lower risk of harm than does an intrathecal medication.

Because the vast majority of those performing sterile compounding do not perform high-risk (nonsterile to sterile) compounding, I favor an approach whereby <797> would focus on sterile to sterile compounding requirements exclusively. The creation of an additional chapter specifically devoted to nonsterile to sterile compounding would simplify <797> for the majority of users while simultaneously allowing for a comprehensive approach to the metrics necessary for the safe compounding of high-risk CSPs.

Another major change to the chapter involves the scope of practice. The current chapter relegates the reconstitution of vials (ie, according to their package insert directions) to less than low-risk compounding. The proposed language allows this low-risk compounding activity to be done in uncontrolled environments if aseptic technique is followed. This proposed revision could result in the transfer of compounding to the bedside or nursing unit, bypassing pharmacy altogether. In this scenario, there is significant risk for a reemergence of a broad range of medication errors. In addition, there is no definition of the expectations for aseptic technique; this clarification is needed to keep patients safe.

The changes to environmental monitoring requirements must be examined within context: Are the changes too much or not enough? The current requirements for conducting air sampling twice a year offers limited utility since it does not provide sufficient data points to verify a state of control. Demonstrating a state of control requires more data in order to identify trends. More frequent environmental monitoring allows for early detection and correction before patients are harmed. In my opinion, medium-risk operations necessitate monthly monitoring of air, surface, and gloved fingertip testing sampling (see TABLE 1).

Likewise, pharmacy staff performing medium-risk compounding should undergo semi-annual evaluations encompassing media fills, didactic, and observational assessments (see TABLE 2). However, for operations performing nonsterile to sterile (high-risk) compounding, I do not believe monthly sampling is sufficient. For these high-risk compounding operations, weekly environmental and personnel sampling should be required.

PP&P: How will <797> and <800> be harmonized?

Kastango: The two chapters will be harmonized as part of the revisions to USP <797>. Each chapter will refer to the other as needed. All pharmacies that compound hazardous drugs are expected to comply with all elements of <797> in addition to all of the hazardous drug-specific requirements in <800>.

PP&P: What timeline is likely for <797> publication?

Kastango: According to the USP Web site, the earliest that General Chapter <797> may be published is November 1, 2016 in USP 40-NF35, with the earliest official date of May 1, 2017. However, please note that this is highly dependent on the quantity and complexity of the public comments submitted on the chapter. It is quite possible that there will be a second comment period as we saw with <800>, given the large number of comments the committee received that now must be evaluated. Based on my review of the proposed revisions, the chapter still needs work. For example, some of the critical performance activities were removed in the initial revision, including the requirement that CETA Application Guides be used for the certification of primary and secondary engineering controls. Without clear guidance on the appropriate tests required for testing primary or secondary engineering controls, pharmacists may get incomplete or incorrect data and not know if their PECs/SECs comply with the performance criteria of the chapter, which can put patients at risk. Because the reference to the CETA standards was extensively vetted by the USP, FDA, PEC/SEC vendors, certifiers, and practitioners prior to being included in the 2008 revision, I feel this should not be removed.

Likewise, there are myriad technology solutions utilized during the compounding process, including IV workflow/verification hardware and software and various robotic devices. Clear guidance on how to qualify these technologies and ensure that they do not negatively impact the quality of compounded sterile preparations is currently missing from the revised version of <797>.

PP&P: How do you expect regulatory bodies to incorporate the changes to <797> in their inspections?

Kastango: The period immediately following the publication of a revision can be confusing for regulators and stakeholders alike. Until the revisions are finalized (ie, published with an official enforcement date) pharmacy must continue to follow the current version of USP Chapter <797>, which can be found in USP 38-NF 33. Once the proposed chapter is finalized—and I certainly expect to see changes to personnel and environmental sampling as well as reductions to BUDs—the regulatory bodies are likely to incorporate the changes into their compliance standards. Keep in mind that <797> establishes the minimum standard of compliance and pharmacies can always make the choice to exceed the standards in the pursuit of implementing best practices.

PP&P: What steps can pharmacy take now in the pursuit of safe CSP practices?

Kastango: To start, pharmacy should establish how well they comply with the current chapter. There are a number of gap analysis tools that can be used to determine the current state of compliance. The next step is to review not only what the chapter requires, but also the reasons behind those requirements. This knowledge can then be leveraged to drive an action plan to close any compliance gaps. Ultimately, pharmacy must ensure that hospital leadership supports their efforts and provides the appropriate resources to attain compliance with these regulations.

Because <797> is considered a national standard of care, there are legal risks to noncompliance, especially for the pharmacist-in-charge or manager of record. Consider that <797> also is a patient-safety document; you may not agree with everything in the chapter, but compliance is not optional. As such, there should be a sense of urgency in integrating the chapter and its updates into pharmacy’s daily operations.


Eric S. Kastango, MBA, RPh, FASHP, is the president, CEO, and owner of Clinical IQ LLC, a provider of customized process and educational strategies for the pharmaceutical, medical device, and health care industries. Eric received a coveted ISMP Cheers Award in 2015 for his work related to sterile compounding safety.

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