USP Enforcement Status Update

November 2019 - Vol.16 No. 11 - Page #14

Q&A with James A. Jorgenson, RPh, MS, FASHP,
Chief Executive Officer and Chairman of the Board
Visante, Inc, and Visante Limited

Pharmacy Purchasing & Products:
How do the appeals to USP Chapters <797> and <795> impact current compounding compliance efforts?

James A. Jorgenson, RPh, MS, FASHP: Since the revised <795> and <797> are now postponed pending appeal, there is no immediate impact on current compounding compliance efforts; sites should ensure that they are in full compliance with the existing versions of USP <795> (2014) and USP <797> (2008).

PP&P: What is the scope of the items under appeal?

Jorgenson: USP is considering appeals for the following three topics under USP <795> and <797>:

  1. Beyond-use date (BUD) provisions in both chapters
  2. Removal of the alternative technology provision from USP Chapter <797>
  3. Applicability of both chapters to veterinary practitioners

It is important to note that Chapter <825> is also under appeal in terms of compounding from sterile and nonsterile radiopharmaceuticals and the applicability of <825> within the radiopharmaceutical regulatory context.

PP&P: Is there a timeline as to when USP will respond to the appeals?

Jorgenson: To date, a definitive timeline has not been released; however, USP is working on completing the appeals process as expeditiously as possible. I recommend operating under the assumption that this is likely to be a brief delay; pharmacy should be ready to demonstrate full compliance to the 2019 chapters in short order.

PP&P: Are there likely to be additional changes to the chapters resulting from USP’s review, beyond the issues currently under appeal?

Jorgenson: Not that I am aware of at this point. I highly encourage pharmacists to sign up for updates through USP’s website and monitor all of the postings as this process evolves:

PP&P: How are state boards and accrediting bodies expected to respond to this postponement from USP?

Jorgenson: It appears the majority of state boards that have already adopted <797> will wait for the release of the revised chapter and will not move forward with revisions to their rules and regulations until the new chapter is finalized with no pending appeals. However, since General Chapter <800> is not subject to any pending appeals, it will become official on December 1, 2019. It is important to note that during the postponement and pending resolution of the chapter appeals, USP has stated that <800> is informational and not compendially applicable.

Nonetheless, some states, such as Iowa, will be enforcing <800> in its current form as of December 1. The Iowa Board of Pharmacy has further clarified that those facilities current with the 2019 requirements for <797> and <795> can operate under those regulations, while facilities that have yet to achieve full compliance may continue to operate under the current chapters until USP finalizes the chapter. Basically, each entity has the option of deciding which version of the chapter they will be inspected under.

Sites should look to their state regulating bodies for guidance. It is clearly highlighted in the USP announcement that “USP encourages utilization of <800> in the interest of advancing public health,” an interest we should all foster.

PP&P: For the time being, how would you recommend pharmacies approach BUDs?

Jorgenson: Facilities should ensure that their BUDs are in full compliance with existing <795> and <797> standards as well as any specific state board standards until such time that the new chapters are released. Given USP’s Notice of Intent to Revise, the 2008 <797> risk assessment based on preparation/product process should remain as the basis of BUD preparation until otherwise directed by USP to utilize the proposed risks categories (ie, Category 1 and Category 2). In addition, facilities should follow any guidance provided by their state regulatory agencies.

PP&P: During this appeal period, what efforts should pharmacy focus on to ensure safe compounding practices?

Jorgenson: Since the primary element of the <795> and <797> appeals impacts BUDs, sites should continue to work to enhance all other elements of their programs to meet the new chapter requirements, as it is unlikely that anything outside of the current appeal will change. For example, assigning an expert, removing excess clutter from compounding spaces, enhancing cleaning programs, conducting monthly viable surface testing, and creating or updating master formulation records and compounding records are all examples of processes that sites should be working to achieve.

Likewise, USP Chapter <825>, which provides guidance for the management of radiopharmaceuticals, should not be overlooked. Pharmacy should be working with the nuclear pharmacy or radiology department to coordinate compliance plans for this new chapter.

Those facilities that have already upgraded their compounding operation for compliance with the 2019 updates are now operating under more rigorous standards, and should continue to do so. Creating a safer environment than the current standards require certainly is not going to cause any compliance challenges. Conversely, those facilities that have not yet achieved full compliance to the 2019 chapters now have an opportunity to catch up, and this opportunity should not be squandered.

For next steps, a strong focus on <800> is recommended as this chapter may be enforced by state boards before the appeals are resolved. Thereafter, assuming that facility upgrades have occurred, there are key areas in the chapters under review that should be addressed, including issues encompassing personnel, environmental monitoring, and standard operating procedures (SOPs).

PP&P: What are some of the key personnel-focused changes in the new chapter?

Jorgenson: The following new requirements are designed to help avert practice drift:

    • A visual observation of hand hygiene and garbing must be conducted every 6 months, rather than annually.
    • A gloved fingertip and thumb test must be conducted at initial orientation and every 6 months thereafter, rather than annually.

  • A media fill test must be conducted and passed at orientation and every 6 months thereafter. Furthermore, a failed test requires three successful repeats prior to restarting.
  • The individual must pass all competencies prior to being permitted to prepare patient doses.

Click here to view a larger version of this Figure

PP&P: What steps should pharmacy take to update environmental monitoring practices?

Jorgenson: The 2019 revisions to USP <797> include more frequent microbiological environmental monitoring requirements. Sites should work to ensure that robust documentation and compliance monitoring systems are in place to support the enhanced monitoring requirements.

It is important to review the new section entitled “Microbiological and Surface Monitoring,” which encompasses the requirements for environmental monitoring. Key changes include:

  • The timeline for viable and non-viable air sampling remains the same (ie, every 6 months) and can continue to be performed by certifying bodies; conversely as a best practice, sites can bring this process in-house.
  • Surface viable sampling has changed: monthly sampling is now required. Sites should refer to historical surface sampling maps and emulate the locations to create meaningful data trends.
  • The surface sampling action level for ISO Class 8 is now defined at >50 CFU/sample, which requires that any microorganism recovered be identified.
  • To ensure containment of hazardous drugs under USP <800>, environmental wipe sampling to detect uncontained hazardous drug residues should be performed routinely (eg, initially as a benchmark and at least every 6 months thereafter, or more often as needed, to verify containment). However, with the emergence of new rapid detection technology, sites have the ability to test more frequently.

PP&P: What are the key elements to include in an out-of-specification results response plan?

Jorgenson: Most important is establishing a formal program to address and document the process. The pharmaceutical industry utilizes the process of Corrective Action and Preventative Action (CAPA) to formally document and trend out of specification events, which can serve as a model for pharmacy.

One of the best programs that we have seen is the one established at Massachusetts General Hospital, which is well organized, well documented, and addresses all of the key elements. They utilize an electronic system to capture, document, and trend these events, which are then subcategorized by cause as one of the following:

  • Environment
  • Personnel
  • Product
  • Other

The sample form in FIGURE 1 captures the key components for addressing out-of-specification events, which must include:

  • Reporting person
  • Date received
  • Nature of complaint
  • Response to complaint
  • Name/strength of product
  • Internal ID number of product
  • Quarantine and destruction
  • Date completed (this is key to demonstrate completion of the out of specification event versus lingering events with no resolution)

PP&P: What changes should be made to policies and procedures?

Jorgenson: SOPs must be reviewed at least every 12 months. If the facility defined review periods differ, they must be adjusted to meet the USP standard. It is important to ensure that the SOPs reflect the actual practices on site and that the actual practices emulate the USP standards.

Commercially available SOPs may be purchased to serve as a guidance document. However, if the templated SOPs are not modified to match actual site practices, this could lead to accreditation and regulatory compliance issues.

Access to SOP master documents must be limited. The individuals who are permitted access to the working document should be clearly defined and all changes should be documented and dated. The pharmacist in charge should ensure that a formal change, approval, and posting process is in place, and that rogue changes to SOPs cannot occur.

Once SOPs are revised, a formal process must be in place to communicate changes to staff. Simply emailing and posting the new SOP is insufficient; a more formal process introducing the changes should be in place and include documentation that the communication was received and acknowledged by staff.

PP&P: Should we stop using the terms CAI and CACI?

Jorgenson: Yes, compounding aseptic isolators (CAIs) and compounding aseptic containment isolators (CACIs) are now classified as restricted access barrier systems (RABS). RABS are defined in USP <797> (2019) as:1

An enclosure that provides HEPA-filtered ISO Class 5 unidirectional air that allows for the ingress and/or egress of materials through defined openings that have been designed and validated to preclude the transfer of contamination, and that generally are not to be opened during operations. Examples of RABS include CAIs and CACIs.

A pharmaceutical isolator is defined by USP <797> as:1

An enclosure that provides HEPA-filtered ISO Class 5 unidirectional air operated at a continuously higher pressure than its surrounding environment and is decontaminated using an automated system. It uses only decontaminated interfaces or rapid transfer ports for materials transfer. [Note—A CAI or CACI is not a pharmaceutical isolator.]

Any mention of “isolator” within USP <797> (2019) refers to a pharmaceutical isolator, not CAIs and CACIs. Historical exemptions to practices connected to the older isolator terminology are removed in USP <797> (2019).

PP&P: How would you recommend facilities approach the “shoulds” in USP <797>?

Jorgenson: Every “should” should be in place. Because standards never lessen—they only advance—we can safely assume that over time some of the “shoulds” will become “musts.” All compounding planning must begin with an acknowledgement of the very first sentence in <797>:1

This chapter describes the minimum standards to be followed when preparing compounded sterile human and animal drugs [compounded sterile preparations (CSPs)].

Our patients deserve more than the minimum standards of care.

James A. Jorgenson, RPh, MS, FASHP, is chief executive officer and chairman of the board of Visante, Inc, and Visante Limited. Before joining Visante, Jim was chief pharmacy officer and vice president of Indiana University (IU) Health, where he was responsible for the design and operation of the system’s pharmacy services supporting IU Health’s integrated delivery network. He is a member of PP&P’s Editorial Board.


  1. USP General Chapter <797>. Pharmaceutical Compounding – Sterile Preparations. Second Supplement to United States Pharmacopeia and National Formulary (USP 42-NF37). June 3, 2019. Accessed October 15, 2019.


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