JerryFahrni.com Podcast | Episode 10: Hazardous Drug Compounding

Show Notes:
Host: Jerry Fahnri, Pharm.D.

Short updates for the week ending March 26, 2016. I briefly touch on USP <800>, DrugCam semi-automated iv workflow management system, and the Grifols KIRO Robot

Items discussed in podcast:

Current setup:
Blue Microphones Yeti USB Microphone – Blackout Edition
Dragonpad Pop Filter
Sony MDR-V150 Headphones

Recommendations for technology-assisted CSP preparation

Both ISMP and ASHP are working on draft recommendations for technology in the IV room. ISMP’s version is an update to their ‘Guidelines for Safe Preparation of Sterile Compounds’ that was originally published in 2013. The proposed revision is open for public comment until April 10th. ASHP is also working on new recommendations for the use of IV Workflow automation technology for the preparation of compounded sterile products (CSPs)

It feels a bit like running into a burning building to pull people out instead of taking action to prevent the building from catching fire in the first place, i.e. reactive instead of proactive. Many of us have known for years that there’s a problem in the IV room. It’s the dirty little secret of the industry. We’ve been saying that change is needed, but it has mostly fallen on deaf ears until now. What’s changed? I have an opinion, but that’s for another time.

We’ve known for decades that the IV room is not only one of the busiest areas in a pharmacy but also one of the most dangerous. IVs present higher risks than most other medications and the literature presents abundant evidence of the prevalence of pharmacy compounding errors, (1, 2, 3, 4, 5, 6, 7) which result in patient harm or death. (8,9, 10, 11) These errors not only impact patients but caregivers and healthcare facility as well. The human and financial toll are staggering.

While we may think we don’t make mistakes in the IV room, studies have shown that errors during CSP production are not uncommon. According to the frequently cited article by Flynn, Pearson, and Baker published in 1997: “A five-hospital observational study on the accuracy of preparing small and large volume injectables, chemotherapy solutions, and parenteral nutrition showed a mean error rate of 9%, meaning almost 1 in 10 products was prepared incorrectly prior to dispensing.” (7)

Many of the errors found with CSPs can be easily prevented through the use of common, currently available technologies. While adoption of technology has been slow, pharmacies are increasingly moving toward the use of these systems. Guidelines from ISMP and ASHP will certainly help speed things up.

Compliance with USP <797> Pharmaceutical Compounding—Sterile Preparations and ASHP Guidelines on Quality Assurance for Pharmacy-Prepared Sterile Products has certainly led to improved processes and safety in the IV room. Both address the need to accurate identify, measure, dilute, mix, package, and label CSPs. However neither of the guidelines is designed to drive adoption of CSP technologies to improve safety, accountability, and documentation.

The quality and safety of CSPs goes beyond sterility, potency, and stability and must include accurately identified and measured ingredients, diluents, final solutions, and containers as well as identifying, tracking, and documenting the CSP from cleanroom to patient.  Current practices do not support or encourage the use of available automation and technologies to support these activities.

Much has yet to be defined and there are currently no guidelines or governing entities to drive standardization for vendor development and design, nor is there anything to help healthcare systems make smart choices.* With that said, it appears that changes are just around the corner.

During this time, it is important to understand the following:

  • Vendors must design – and users chose – systems that provide a clear advantage over manual systems in patient safety, workflow standardization, and documentation; are cost-effective; interoperable with existing systems; are simple to install, use, and maintain; and carry a high degree of certainty and reliability.
  • Minimum requirements** should include interoperability with pharmacy information systems and electronic health records, control of final product label, bar code verification of all ingredients and final containers, imaging for verification and documentation, documentation of master formula records, lot numbers, expiration dating, and products used, and basic dose tracking functionality.
  • While some of the products available today generate their own ISO class 5 compounding environment, these systems must function properly in cleanroom environments and comply with all USP <797> and <800> standards and recommendations.
  • And finally, technologies for CSP production must be correctly selected and utilized to effectively create a safe environment for both the healthcare provider and the patients they serve. There is no one-size-fits-all approach to these systems and each healthcare system is different. Proper selection will depend on several factors.

It’s time for vendors and healthcare systems to wake up and get ready for what’s coming.

References

  1. US Food and Drug Administration Website. Report: Limited FDA Survey of Compounded Drugs. Available online at: http://www.fda.gov/cder/pharmcomp/survey.htm. Accessed on January 3, 2004.
  2. United States Department of Justice, Federal Bureau of Investigation Website, April 22, 2002. Available online at: http://kansascity.fbi.gov/kcmostate042202.htm. Accessed on July 6, 2002.
  3. Trissel LA. “Compounding our problems–again.” Am J Health-Syst Pharm. 1 Mar. 2003: 432.
  4. Selenic D, Dodson DR, Jensen B et al. “Enterobacter cloacae bloodstream infections in pediatric patients traced to a hospital pharmacy.” Am J Health-Syst Pharm. 2003; 60:1440–6.
  5. Niedowski E, Bor J. State to probe Hopkins death: 2-year-old cancer patient died after receiving improper IV mixture. December 20, 2003. Baltimore Sun, Baltimore, MD.
  6. Flynn, EA, Pearson, RE, Barker, KN. “Observational study of accuracy in compounding IV admixtures at five hospitals.” Am J Health-Syst Pharm. 1997 Apr 15; 54: 904–912
  7. Solomon SL, Khabbaz RF, Parker RH, et al. “An outbreak of Candida parapsilosis bloodstream infections in patients receiving parenteral nutrition.” J Infect Dis 1984; 149:98–102.
  8. Hughes CF, Grant AF, Leckie BD, et al. “Cardioplegia solution: A contamination crisis.” J Thorac Cardiovasc Surg 1986; 91:296–302.
  9. Associated Press. Pittsburgh woman loses eye to tainted drug; 12 hurt. Baltimore Sun. November 9, 1990:3A.
  10. Dugleaux G, Coutour XL, Hecquard C, et al. “Septicemia caused by contaminated parenteral nutrition pouches: The refrigerator as an unusual cause.” J Parenter Enteral Nutr 1991; 15:474–475.
  11. Perrin J. “Unsafe activities of compounding pharmacists.” Am J Health-Syst Pharm 1995;52:2827–2828.

*Actually, I would argue that IN THE CLEAN ROOM: A review of technology-assisted sterile compounding systems in the US (Jerry Fahrni, Pharm.D. and Mark Neuenschwander) would be a great tool for helping pharmacies make smart choices, but most seem averse to the information.

**Minimum requirements. This is not to say that this should be the end game, but rather a place to start. Overreaching in the beginning of this process is sure to dampen development and adoption.

General Chapter 800 Commentary posted

Just in case anyone was interested and wanted to get a jump on the upcoming USP Chapter <800>.

The USP-NF Compendial Update for February included General Chapter <800> Commentary, which was posted on February 1, 2016. It’s a PDF document that includes all the comments that were submitted for consideration to the Expert Compounding Committee. The document can be found here.

If you want to get a sense of what’s going to be in the chapter, just open it up and search for ‘comment incorporated’. There are just over 100 items. On the flipside, if you want to see what was rejected search for ‘comment not incorporated’. My search found more than 200 items that were rejected. Too bad, really. I thought some of the items that were kicked to the curb were pretty good ideas.

Will the revised USP Chapter 797 include recommendations for automation and technology?

Whether or not future editions of USP General Chapter <797> will include recommendations for IV room automation and technology is a great question, and one that I’ve been pondering for quite some time. I’m torn as to whether or not I think adding such recommendations to a USP General Chapter is a good idea.

On one hand, I believe that pharmacy is over-regulated as it is. The amount of time spent by pharmacy personnel adhering to and documenting compliance to regulations currently in place is staggering. New regulations are frequently added to the process, but rarely, if ever taken away.

On the other hand, pharmacies refuse to utilize game-changing automation and technology even when they know it has the potential to improve operations, improve patient safety, and decrease cost. I’ve met many pharmacy directors and operations managers over the years that operate in a state of willful blindness when it comes to adoption of technology in the pharmacy.

While I don’t support adding, even more, regulatory requirements to pharmacy practice, I’m in favor of increased use of pharmacy automation and technology, especially in the IV room. It’s a conundrum.

With that said, it may become a moot point as it is possible that recommendations addressing the use of iv room automation and technology will find their way into the next revision of USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. Recent discussions with people close to the situation lead me to believe it could happen.

Should that occur, it would likely be a good thing for pharmacy practice in the long run as it would drive adoption of CSP preparation technology. Even if the Expert Compounding Committee were to recommend adoption and not mandate it, i.e. “should” versus “shall”, the industry would surely take note. Recommendations that show up in <797> have a way of trickling down into other regulatory agencies as well as into the minds of inspectors and pharmacy directors. For example, the 2015 California Lawbook for Pharmacy(1) states that “The board shall review any formal revision to General Chapter 797 of the United States Pharmacopeia and The National Formulary (USP–NF), relating to the compounding of sterile preparations, not later than 90 days after the revision becomes official, to determine whether amendments are necessary”. Regardless of whether or not the board takes action, they are sure to take notice.

It’s too early to say whether or not the revisions to Chapter <797> will include recommendations for CSP preparation technology, but I suspect we won’t have to wait long to find out. Chapter <797> is currently up for public comment until January 31, 2016. Based on recent changes to USP General Chapter <800>, I suspect revisions to Chapter <797> will become official in a similar timeframe so that the chapters can be properly harmonized. Only time will tell.

Something worth thinking about.

———–

(1) Article 7.5, Section 4127(c)

USP General Chapter <800> has been approved

I’m sure that most of you are aware, but just in case, I thought I would pass this little tidbit along.

The Compounding Expert Committee announced on November 20, 2015, that USP has approved a new General Chapter USP <800> – Hazardous Drugs—Handling in Healthcare Settings. The revised chapter will be published February 1, 2016, in the first supplement to USP 39-NF 34. USP standards typically become official 6 months after publication, but the Expert Committee approved a delayed official implementation date of July 1, 2018 to prevent any undue hardship on systems that need to make major changes.

You can get more information on General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings to be Published in USP 39–NF 34, First Supplement here.

Good luck, people.

Major differences between proposed USP Chapter 800 and current USP Chapter 797

USP <800> is still in draft form. The official date of the chapter has not yet been determined and is dependent on several factors, but expect it to become official some time in mid to late 2016. And while USP <797> is in the process of being updated, the current version is still the one everyone has to live with.

Information contained in USP <800> is in addition to information found in USP Chapter <797> Pharmaceutical Compounding – Sterile Preparations and USP Chapter <795>  Pharmaceutical Compounding – Nonsterile Preparations.

In its current iteration, USP <797> and USP <800> requirements for hazardous drugs (HDs) differ.  However, HD compounding in the upcoming revision to <797> will be harmonized with Chapter <800>. Actually, it looks like USP will simply defer all HD compounding to USP <800>, which makes sense.

Until all the USP Chapters are on the same page, here are some highlighted differences between Chapters <800> and <797>:

  • Requirement of compounding supervisor
  • Applies to sterile as well as non-sterile compounding
  • No longer allowed to store, unpack, or manipulate HDs in positive pressure areas
  • Elimination of exemption that allowed low volumes of HDs to be compounded in a non-negative pressure room. All quantities of HDs must be compounded in a separate, negative pressure room
  • C-SCAs may be used to compound low- and medium-risk HDs
  • CSTDs are recommended for compounding and required for administration

Perhaps the greatest impact will come from elimination of the current USP <797> exemption for small volumes of HDs to be compounded in a positive pressure room. USP <800> handles this by allowing low- and medium-risk HDs to be compounded in a containment segregated compounding area (C-SCA). C-SCA is a new concept, and is defined as “a separate, negative pressure room with at least 12 air changes per hour (ACPH) for use when compounding HDs. Low- and medium-risk HD compounded sterile preparation (CSP) may be prepared in a BSC or compounding aseptic containment isolator (CACI) located in a C-SCA, provided the beyond-use date of the CSP does not exceed 12 hours“.