Q&A with
Patricia C. Kienle, RPh, MPA, FASHP,
Director of Accreditation and Medication Safety
at Cardinal Health 

Pharmacy Purchasing & Products: What is the current status of proposed USP Chapter <800>? 
Patricia C. Kienle: Based on public comments received for the originally proposed USP General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings published in Pharmacopeial Forum (PF40[3] May-Jun 2014), the USP Compounding Expert Committee developed a revised chapter (available online at http://www.usp.org/sites/default/files/usp_pdf/EN/m7808_pre-post.pdf). The expert committee incorporated changes resulting from the previous public comment period and is seeking another round of feedback. The revised chapter was posted in December 2014 on the USP Web site and also will be published in the March-April 2015 issue of the Pharmacopeial Forum. The new public comment period for the revised chapter is open until May 31, 2015. 

PP&P: Did the expert committee make a significant number of changes in response to the first round of public comment? 
Kienle: Yes, in fact wording changes were made in almost every section of the chapter. While these were primarily to further clarify or explain points on which we received comments, some significant changes were incorporated as well (see BOX 1). I commend pharmacists for their commitment to this topic; the expert committee received a multitude of thoughtful comments and suggestions on the original draft, which clarified what needed to change in the chapter. It is my hope that pharmacists will remain equally engaged in this round and will submit comments on the recent revisions, as this is our opportunity to make USP <800> as clear as possible. 

PP&P: Are there differences between <797> and <800>?
Kienle: One important issue that was part of the original <800> proposal and that remains unchanged is that USP <797> allows low-volume compounding of hazardous drugs (HDs) in a positive-pressure room, but proposed USP <800>, both before and after revisions, does not. All HD compounding must be conducted in a separate designated area, and it cannot occur in a positive-pressure room. 

USP <800> eliminates the low-volume exemption in <797>, but provides a different way for entities to comply. The best option still is to use a negative-pressure cleanroom for compounding HDs, but for organizations that may not have a negative-pressure cleanroom (eg, small hospitals or oncology clinics), USP <800> includes an allowance to use a containment segregated compounding area (C-SCA). This is a separate, negative-pressure room that is vented to the outside and has at least 12 air changes per hour, but it does not need to meet International Organization for Standardization (ISO) cleanroom standards. 

There is an important caveat that accompanies this exception: Proposed USP <800> limits the beyond-use dating of HDs compounded in a C-SCA to 12 hours, similar to what <797> allows for compounding nonhazardous drugs. So while compounding in a C-SCA is less expensive than building a negative-pressure cleanroom, the trade-off is the shorter beyond-use date for IVs compounded therein. This 12-hour limit may not be a problem for IV chemotherapy production, as these medications typically are not produced until the patient arrives and is cleared for treatment. 

PP&P: What is new in the containment requirements for HDs? 
Kienle: The revised chapter includes a new explanation in section 2, List of Hazardous Drugs. Following the release of the original USP <800>, the National Institute for Occupational Safety and Health (NIOSH) updated their list of HDs, which are now stratified into three categories: antineoplastics, non-antineoplastics, and reproductive hazards only. In response, the revised USP Chapter <800> stratifies the containment requirements into those same categories (see BOX 2). 

So, when handling an antineoplastic drug that requires manipulation—such as mixing an IV or compounding from an active pharmaceutical ingredient (API)— a hospital or other setting (an entity) must use all the containment strategies listed in USP <800>. When handling non-antineoplastic HDs or those HDs that are reproductive hazards only, entities can opt instead to conduct an internal assessment of risk to determine if their practices ensure safe HD handling. An assessment of risk approach also can be taken for antineoplastic agents that do not require any manipulation other than counting or dispensing an intact package (such as methotrexate tablets).

This internal assessment may determine that no change is required to the current handling practices for a non-antineoplastic or an agent that is a reproductive hazard only. The risk assessment must be specific to the drug and dosage form and include the containment strategies in use and/or those that will be implemented to ensure safe handling. The written assessment should describe the format in which the product is provided and detail the work practices used during handling. If all the requirements can be sufficiently addressed, then the agent may not need to be stored separately, may not need to be prepared in a negative-pressure room, and may not require different labeling for the patient. Again, this is permitted only for HDs on the list that are not antineoplastic (unless in final dosage forms) and that are not APIs. 

Oxytocin is a good example of such an HD. Widely used, oxytocin is found in any hospital that has an obstetrics department, but by NIOSH’s definition, it is an HD because it poses a reproductive hazard. A hospital’s assessment of risk for oxytocin could include, for example: We buy the FDA-approved dosage form in a vial. We buy a premixed IV bag from an FDA-registered outsourcing facility. The few doses we prepare are prepared under controlled conditions. Our employees know oxytocin is a reproductive hazard. We dispense doses only in a final form: an IV bag that nurses and doctors can administer. We do not use powder; we do not open vials; we do not expose people unnecessarily. 

The revisions in section 2 of the proposed chapter address many concerns pharmacists raised about the original chapter, two of the most prominent being that oxytocin was listed as an HD, which meant that hospitals not providing chemotherapy, but offering obstetric services, were subject to USP <800> standards, and the second concerning preparation of antipsychotic agents for administration and how patients might react to staff utilizing additional personal protective equipment and medication prominently labeled as hazardous. 

The bottom line is that entities cannot claim that drugs listed by NIOSH as non-antineoplastics or reproductive hazards are not hazardous; they are hazardous, and their employees need to know that. However, entities can go through their policies and identify, by drug and dosage form, the containment strategies and work practices they will implement to ensure safe handling of those agents that are antineoplastics that do not require any manipulation other than counting, and those HDs that are non-antineoplastics and reproductive hazards only. 

PP&P: Does the revised chapter discuss the requirement for external venting for nonsterile compounding? 
Kienle: Revised USP <800> includes a change in the requirement for venting for nonsterile compounding. The original proposal required external venting of the containment primary engineering control (C-PEC) used for nonsterile compounding. The revision emphasizes that external venting of the C-PEC is preferred for nonsterile compounding, but adds the option of substituting with redundant high-efficiency particulate air (HEPA) filters in series. Particle generation is the main concern with nonsterile compounding, and redundant HEPA filters are designed to contain any powders. 

If an organization is building a new space for nonsterile compounding, external venting is the best and safest choice, but an option now exists for entities that cannot provide venting to the outside. Requirements for sterile compounding remain the same in the original proposal and the revision, with only minor wording changes to enhance clarity.

PP&P: What other changes did the expert committee include in the revised <800> proposal?
Kienle: The statement that said there is no acceptable level of personnel exposure to HDs was removed. Although the statement is accurate, it was removed because, from a regulatory perspective, organizations might be held to a higher standard than they could possibly meet. 

In addition, the original proposal stated that drug unpacking should not occur in a positive-pressure area. While this is still the case in the revision, the wording has been changed. The wording now indicates that drugs can be unpacked either in a negative-pressure area or in a neutral-pressure area—just not in a positive-pressure area. This is to prevent the dispersal of contamination that may exist on the packaging. 

Also, the cleaning section has been updated to more clearly delineate the cleaning tasks that need to occur and the order in which they need to be performed, particularly as those tasks relate to deactivating an HD or decontaminating an area where an HD may have been. The original proposal only discussed using sodium hypochlorite (bleach) for cleaning. In the revised proposal, the language has been broadened to allow for the use of other commercially available agents approved by the Environmental Protection Agency for use in the decontamination of HDs.

PP&P: What is the timeline for entities to implement changes to meet the new standards and what should they be doing now to prepare?
Kienle: Because the proposed chapter was posted earlier than when it will be published in Pharmacopeial Forum, USP is providing a total of six months for comments on revised chapter <800>. It is premature to predict when the standard will be published and become official, since it depends on several factors, including the nature and significance of the public comments received, whether any further revision is required, and whether a delayed implementation period is approved. A delayed implementation would provide entities additional time in order to come into compliance with the chapter. The official date for the chapter may be in 2016 or 2017. Furthermore, enforcement is dependent on adoption by regulatory bodies, such as state boards of pharmacies. 

As far as what can be done now, pharmacists should read the revised proposal of USP <800> and provide any further comments, as necessary. Pharmacy leaders are understandably concerned with requirements that could impact facility design, which require capital and long-term planning, but until the final version of USP <800> is published in USP-NF, it may be premature to plan significant infrastructure renovations. It is clear, however, that the low-volume exemption is going away. Entities that are using it now must prepare a proper place to compound their HDs and should not wait until USP <800> is final to begin to address this issue.

Patricia C. Kienle, RPh, MPA, FASHP, is a member of the USP Compounding Expert Committee and chair of the Hazardous Drug Subcommittee and Expert Panel, although her comments here are her own and not official information from USP. 

BOX 1
Major Changes in Proposed USP Chapter <800> Resulting from the First Public Comment Period

• Clarified wording in many sections
• Removed statement concerning no acceptable level of personnel exposure to HDs
• Revised section on list of HDs, allowing entities to perform an assessment of risk for non-antineoplastic drugs and reproductive risk-only HDs to determine alternative containment strategies and/or work practices 
• Clarified that HDs may be unpacked only in a neutral-, normal-, or negative-pressure area 
• Allowance for either external venting or redundant HEPA filtration in C-PECs used for nonsterile compounding

USP Web site. General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings. http://www.usp.org/sites/default/files/usp_pdf/EN/m7808_pre-post.pdf. Accessed January 12, 2015.

BOX 2 
Containment Requirements 

• Any antineoplastic HD requiring manipulation and HD API on the NIOSH list must follow the requirements in this chapter.
  • Final antineoplastic dosage forms that do not require any further manipulation other than counting final dosage forms may be dispensed without any further requirements for containment unless required by the manufacturer.
• For dosage forms of other HDs on the NIOSH list, the entity may perform an assessment of risk to determine alternativecontainment strategies and/or work practices.

USP Web site. General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings. http://www.usp.org/sites/default/files/usp_pdf/EN/m7808_pre-post.pdf. Accessed January 12, 2015.