Complying with USP <800>

December 2021 - Vol.18 No. 12 - Page #2
Category: USP Training Programs

Pharmacy Purchasing & Products recently held a webinar entitled:
USP <800> Compliance Update: A Sneak Peek at PP&P’s Latest Data
presented by Fred Massoomi, PharmD, BCSCP, FASHP

The following questions were submitted by attendees.
The webinar slides and full presentation can be downloaded at pppmag.com/webinars.

Q: When will USP <800> and NIOSH 2020 become finalized? Can accreditation bodies or state boards cite an institution for not having implemented the proposed changes?

A: The approval of USP <800> is dependent upon the approval of the proposed revised USP <795> Pharmaceutical Compounding-Non-sterile Preparations and revised USP <797> Pharmaceutical Compounding-Sterile Compounding chapters. The current chapters (as of November 2021) do not reference USP <800>, and the 2008 version of USP <797> has its own section on hazardous drugs (HDs).

Some state boards of pharmacy or equivalent agencies have taken a leading role in employee safety and have incorporated the language of USP <800> into current enforceable standards. Washington, California, New Jersey, and North Carolina are a few of the states that should be commended for taking the lead in protecting health care workers by the early adoption of USP <800>.

We were all given a glimpse of the immediate future approval of the revised USP chapters in October 2021 with the release of the re-revised, proposed USP <795> and USP <797> chapters. The comment period is open until the end of January 2022. As to what happens after that date, it will be up to rational health care providers sharing meaningful and sound comments with the USP Expert Committee, a committee that focuses solely on the safety of the patient, which ultimately leads to the protection of health care providers.

Q: Is the FDA on board with USP <800>?

A: The FDA focuses primarily on cGMPs—current Good Manufacturing Practices. However, they are building an understanding of USP <800> in the context of USP <797> and its impact on public safety.

It would be helpful if the FDA took more leadership in terms of HD safety; for example, establishing a categorical process (like NIOSH) to create a continuously updated list of drugs deemed hazardous to the health care providers who handle them, mandating that HD manufacturers provide the drug vials and corresponding packaging free of HD residue, requiring manufacturers to provide HD drug vials made of material that does not break easily or incorporates a protective covering, and requiring the imprinting of a hazardous symbol on HD vials to alert all health care providers and non-health care providers to the handling risks. This approach is currently part of the drug approval process in Japan, Israel, and Australia; NIOSH petitioned the FDA to add this hazardous drug symbology in the early 2000s.

Q: How do you recommend handling the pending change to the NIOSH HD list where biologics are excluded from the list but still require safe-handling procedures?

A: When the new NIOSH List of Hazardous Drugs in Healthcare Settings becomes official, I encourage sites to read it closely. In the currently proposed version, NIOSH has taken a new stance to the HD list wherein only drugs approved by the FDA’s Center for Drug Evaluation and Research (CDER) will be evaluated for inclusion on the list. Under this proposed change, products approved by the Center for Biologics Evaluation and Research (CBER) will not be included on the HD list. CBER reviews all biologics and related products, such as vaccines, blood products, gene therapies, etc. As such, products like Botox and BCG will no longer be part of the HD list.

Since 2004, NIOSH has provided the health care community with the only comprehensive list of HDs. This move to partitioning the hazardous drug list poses a critical challenge for all health care facilities, as the default may be to not include any HDs on the facility’s HD list if they are not included in the NIOSH list. My hope is that this proposed approach does not remain in the final version.

However, if this approach does remain in the final version, pharmacy departments will need to rely on an assessment of risk to determine safe handling practices for products approved by CBER. For best practice when considering a new product for formulary addition, the assessment of risk must address two key issues. First, conduct a site-specific assessment for the new product that includes all of its dosage forms and considers how and where the drug will be used in your facility. This information will guide how you classify the drug on your HD list. Secondly, review how the drug will be disposed of. While this process is outside of the USP <800> requirements, it is crucial to ensure that every product is disposed of appropriately, via the correct waste stream.

Q: What NIOSH category should investigational drugs be assigned to?

A: Each site must make their own determination as to whether they will classify and handle investigational drugs as HDs. Some facilities classify all investigational drugs as hazardous and utilize negative-pressure spaces to store and handle these products. PP&P’s 2021 USP <800> survey noted that 23% of institutions handling investigational drugs currently take this approach.1 McLeod et al provides excellent guidance on assessing investigational drugs as hazardous risks.2

Because investigational drugs are not fully or partially approved by FDA-CDER, they may not have been reviewed for safe handling implications and may not be included on the NIOSH list. Furthermore, because the NIOSH process for updating the HD list is dated at the time of publication, this leads to gaps as new drugs are approved. In fact, the proposed NIOSH HD list is current to 2015. The overreliance on a published list to serve as the sole source of an institution’s HD list without a concurrent review process for investigational and newly approved drugs leaves a significant gap in the safe handling goals established by USP <800>. As such, NIOSH recommends that “if the mechanism of action suggests that there may be a concern, it is prudent to handle them as hazardous drugs until adequate information becomes available to exclude them” from this designation.3

Read the investigator binder closely. If the handling section is not thoroughly detailed, consider assigning that drug as an HD requiring containment strategies during handling (ie, Group 1/proposed Table 1). In addition, many facilities are looking to utilize CSTDs for those investigational drugs with HD properties. Note that you must receive approval from potential sponsors to use a CSTD with investigational drugs; using a CSTD without clearance may constitute a protocol violation and void your participation.

Q: Is wipe testing for hazardous drug residue a required practice?

A: Wipe testing for environmental HD residues is not required under USP <800>; rather, it is listed as a should, or a recommended practice. Nonetheless, I would highly encourage adopting regular wipe sampling. The data points that result from conducting routine wipe sample provide another tool in the staff safety armamentarium. As institutions make significant financial investments in achieving compliance, wipe sampling provides a straightforward way to validate that investment and demonstrate how effective your facility is in minimizing HD contamination. Certainly, an area that tested negative one day can later show contamination due to a lapse in processes or incomplete spill remediation, for example. In these cases, the results can be leveraged as an educational tool to identify lapses or to reinforce effective processes.

Sites should create a hazardous drug handling committee to review all aspects of the hazardous drug program rather than simply launching a wipe sampling program. To create a successful residue assessment program, the program structure, including staff education and establishing actionable results, must be fully vetted.4

Q: What is best practice for managing spills in delivery vehicles?

A: The best spill strategy is not to have a spill. To accomplish this in delivery vehicles, it comes down to packing. All HD doses in IV bags, syringes, cassettes, elastomeric devices, vials, etc, should be placed in a thick zip lock baggie to help contain any inadvertent spills. Noting that if the dosage form has attached tubing sets, the attached tubing sets may represent a breech point if not packed appropriately.

Packing of these agents should follow the scenario of a raw egg; pack liquid hazardous drugs in a manner equivalent to how one would pack a raw egg for delivery. Consider the use of bubble wrap, Styrofoam pieces, packing peanuts, etc.

Q: Can anterooms be built as a negative pressure space to provide HD storage space?

A: Anterooms as part of a cleanroom suite must be positive pressure and rated to at least ISO 7, with at least 30 ACPH when adjacent to a negative pressure buffer room. Anterooms are not designed to be a drug warehousing/storage area. If sites need storage for HDs, they should formally plan for this storage as a dedicated, externally exhausted, negative pressure storage room with at least 12 ACPH or within the negative pressure buffer rooms.

Refer to your state regulatory agencies with regard to storage of drugs within buffer rooms (positive and negative), as they may not allow this type of storage.

Q: Does the positive-pressure ante area for an HD buffer room require external exhaust, or can it be designed with air return?

A: The anteroom of a cleanroom suite is a positive-pressure rated area that should not have any drugs stored inside. Anterooms can have recycled air through return vents as part of an energy efficient HVAC system. Non-recirculating, external exhaust are only required in the negative-pressure buffer room and, if separate, the HD storage rooms. For containment segregated compounding areas (C-SCAs), rooms where hazardous drugs are stored and compounded must be externally ventilated, negative-pressure rooms with at least 12 air changes per hour (ACPH).

References

  1. State of USP <800> Survey. Pharm Purch Prod. 2021
  2. McLeod EN, Fillis CJ, Blind JE. A practical approach to assess the hazardous exposure potential of investigational drugs. Am J Hosp-Syst Pharm. 2020.
  3. US Centers for Disease Control and Prevention and National Institute for Occupational Safety and Health. NIOSH List of Hazardous Drugs in Healthcare Settings, 2020. https://www.cdc.gov/niosh/docket/review/docket233c/pdfs/DRAFT-NIOSH-Hazardous-Drugs-List-2020.pdf
  4. Duty A, Robinson J, Bahmander D, et al. Creation of a regional hazardous drug handling task force. Am J Health-Syst Pharm 2021;78:1233-1237.

Fred Massoomi, PharmD, BCSCP, FASHP, is senior director of hospital and health-system pharmacy for Visante, Inc. He received his doctorate from the University of Kansas School of Pharmacy. Fred is a member of PP&P’s Editorial Board.

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