In response to national tragedies surrounding compounded sterile medications and acute awareness of the danger of handling hazardous drugs (e.g. chemo); new regulatory standards are being set forth for U.S. hospitals and other compounding sites.
United States standards developing body United States Pharmacopoeia (USP) is revising its standards to help improve safety for both patients and workers, and the revisions are due to go into effect December 1, 2019. The changes impact every area of drug delivery, from receiving dock to disposal of used materials and are far-reaching into the hospital, impacting staff in many areas including facility modification.
New regulations are of critical importance to safety
While the new regulatory standards pose financial, operational and clinical challenges to hospitals, they are indeed important and necessary for the safety of patients, workers and the community at large. The USP, FDA, NIOSH and OSHA all recognize the dangers of mismanaged and incorrectly compounded medications and the inherent risks in handling hazardous drugs. Experts have discovered practices once considered safe are dangerously insufficient or ineffective, putting many individuals at risk.
For example, major modifications to regulations surrounding clean rooms used for compounding sterile drugs mean expensive upgrades may be required to meet the new standards and enhanced standards for personal protection equipment for pharmacy and nursing personnel mean changes in garbing procedures. These are just two examples of how hospitals will need to adapt to achieve compliance with these complex standards.
Specifically, the USP chapters <797> (Pharmaceutical Compounding – Sterile Preparations), <795> (Pharmaceutical Compounding – Non- sterile Preparations), and <800> (Hazardous Drugs – Handling in Healthcare Settings) have established the standards for the compounding of sterile preparations, non-sterile preparations, and safe handling of hazardous drugs respectively in the United States. In March 20181, the USP announced the revision of chapters USP <797> and USP <795>, in addition to the implementation of proposed chapter USP <800>; with an expected compliance date for all three chapters being December 1, 2019. Noting that states can and have enacted compliance with USP chapters prior to the December 1, 2019 date (ex.: California, Washington, New Jersey). Of note, any USP chapter that falls below 1,000 can be enforced by the FDA, adopted by state boards of pharmacy and surveyed against by the Joint Commission.
Many hospitals currently put patients and workers at risk
The challenge for hospitals is that pharmacy departments vary greatly in compliance with these standards. Even with those pharmacies that comply with most elements of the current USP standards, many require a number of modifications to facilities, engineering controls and practices to be considered in full compliance with current and proposed revised USP standards.
Surprisingly, in a recent report by Pharmacy Purchasing and Products, sites reported only a 73% compliance rate with existing USP <797> standards, and only 48% compliant with meeting the new proposed USP <800> requirements2. Oftentimes, pharmacies struggle to comply due to the complexity of the standards, lack of budgets, and the lack of qualified staff. Many hospitals are now under extreme pressure to assess their current situation and implement changes in a timely manner.
More governing bodies getting involved
The establishment of the 2013 Drug Quality Safety and Security Act3 added a new dimension to existing regulations and standards by introducing the FDA into the complexities of sterile products. The act introduced the Title I: Compounding Quality Act and Title II: Drug Supply Chain Security Act. Both Titles of the Act impact the practice of pharmacy with regards to compounding sterile drugs. Over the past two years, the FDA has published for comment greater than 18 Guidance Documents to revise or clarify the Compounding Quality Act with regards to sterile compounding. FDA has taken a more proactive approach to patient safety and has been actively inspecting hospital and clinic locations where sterile drugs are compounded.
Adding another layer of complexity, the proposal of USP <800> brings the Department of Labor and Occupational Safety and Health (OSH) into the vernacular of compounding. The OSH Act of 19704, which sets safety and health standards for United States workers, includes healthcare workers. The OSH Act is administered by Occupational Safety and Health Administration (OSHA), an agency of the Department of Labor (DOL). All employers are subject to the OSH Act have a general duty to provide work and a workplace free from recognized, serious hazards. Since the publications 2004 NIOSH alert5 and proposed USP <800>6 are available in the public domain, handling certain drugs are considered as a ‘recognized’ hazard. And such, sites handling these products must include them in their Hazard Communications Program. USP highlights the OSHA requirement that personnel who may be exposed to hazardous chemicals (drugs; e.g. chemo) when working must be provided information and training before the initial assignment to work with a hazardous chemical (drugs). In addition, this must be modified whenever the hazard changes, such as the addition of a newly defined hazardous drug. USP further specifies, based on the defined risks of certain drugs that personnel of reproductive capability must confirm in writing that they understand the risks of handling hazardous drugs. This statement is directed towards both female and males. It is in the best interest of sites to get a signed agreement on an annual basis confirming education and acknowledgment.
The March 17, 2016 edition of Managed Healthcare Executive listed USP <797> and USP <800> compliance as the top regulations Hospital Executives need to focus on for 2017 . With continuing national drug shortages and the escalating exposure of deficits associated with compounding pharmacies in the wake of the New England Compounding Center disaster, the issue of safe sterile compounding will also continue to receive enhanced scrutiny and regulatory oversight.
If your site has relied on conducting a paper-based gap assessment for assurance of compliance, it should be noted that this is but a minor assessment of practice. Most sites fall short of compliance based on actual practices for assurance of sterility and product integrity. A comprehensive gap analysis that involves a thorough examination of not only current compounding practices but also HVAC, primary and secondary engineering controls, quality practices and elements such as water sources and cleaning processes should be conducted. It is important to do this as soon as possible and to create plans that can be put in place by the December 1, 2019 due date. With over 20,000 clean rooms in the US there will be significant demand for services and products to support required upgrades. Also, while we expect variability in how rigorously state boards of pharmacy enforce the due date we already see evidence that boards are taking this seriously, notably California, Washington and New Jersey have been very active in enforcing current standards. Often sites will defer compounding to compounding outsource manufacturers, however, FDA has issued “cease and desist” orders for sterile compounding, leaving hospitals to revert back to sterile compounding for themselves.8
A major clean room renovation may run at least a million dollars and organizations should very carefully assess and plan for this type of capital investment. It is important to also realize that USP standards are not a static document. The Sterile Products Expert Committee is continuously evaluating and revising these standards and major revisions can be expected every three to four years. Too often organizations plan for upgrades to meet the next level of standards and do not plan beyond that. These standards never get less and are steadily moving in the direction of current good manufacturing practices (cGMP), which are regulated by the FDA. As organizations consider options for facility upgrades they would be well advised to consider not only current standards but also future possibilities and design clean rooms and compounding operations with the capability and flexibility for less costly upgrades as standards continue to evolve.
1 USP; Updates on Compounding Standards. http://www.usp.org/compounding/updates-on-standards ; Accessed March 11, 2018
2 Pharmacy Purchasing and Products Magazine; 2016 State of Pharmacy Compounding: April 2016: Volume: 13 Number: 4 (Supplement)
3 United States Department of Health and Human Services; Food and Drug Administration: 2013 Drug Quality Safety and Security Act: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/pharmacycompounding/ucm536549.pdf ; accessed March 11, 2018.
4 United States Department of Labor; Occupational Safety and Health Administration; Hazard Communication. https://www.osha.gov/dsg/hazcom/index.html Accessed March 11, 2018.
5 NIOSH alert: preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165; http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf Accessed
6 USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings
http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings. Accessed March 10, 2018
7 Maxik, K. Five pharmacy regulations health execs must keep on their radars in 2017. Managed Healthcare Executive.
http://managedhealthcareexecutive.modernmedicine.com/managed-healthcare-executive/news/five-pharmacy-regulations-health-execs-must-keep-their-radars-2017 ; accessed March 11, 2018
California Board of Pharmacy Cease and Desist Order: http://www.pharmacy.ca.gov/enforcement/ipo/ac176247.pdf
8 U.S. Department of Health and Human Services; U.S. Food & Drug Administration.” FDA alerts health care professionals and patients not to use compounded drugs from Cantrell Drug Company; agency seeks action to stop production and distribution” March 1, 2018; https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm599089.htm Accessed March 20, 2018