Tag: USP 797

The impact of COVID-19 on Pharmacy Personal Protective Equipment (PPE)

COVID-19 has taught us many things, among them that our healthcare supply chain is poorly designed and flimsy. Just a few weeks into the pandemic and our supply chain for Personal Protective Equipment (PPE) has been completely disrupted. PPE is now in short supply, and I suspect that we will run out of PPE in just a few weeks if things continue on their current trajectory.

Are we using more PPE because of COVID-19? Of course! But we are unable to spin up production because a vast majority of the products we need are not made in the United States and the world is in lock down. An industry that is literally designed to provide care to others and save lives has no supply chain redundancy, no failover strategy for shortages, and no geographical diversity for equipment and supplies.

Any pharmacy that compounds sterile medications – intravenous antibiotics, for example – is required to wear a lot of PPE. Guidelines have lead to staff being required to wear a clean, low-lint gown, bouffant (head cover), mask, shoe covers, and sterile gloves when entering the buffer area of a pharmacy cleanroom; I also have to wear a beard cover, but most do not.

When leaving the area, a vast majority of the aforementioned PPE gets tossed, i.e. wasted. Up until about a week ago, much of the PPE worn by pharmacy personnel could not be reused. Now, because of the pandemic, regulatory agencies are lifting these restrictions. It’s an interesting shift in thinking.

In general – in theory? – the use of PPE during sterile compounding is designed to decrease risk of introducing bioburden into process. I suppose that makes sense. Unfortunately, the risk has never been quantified to any appreciable manner. There are no before and after statistics to determine whether or not strict adherence to PPE guidelines has done anything to improve sterile compounding safety, or lesson the risk of contamination. One thing is does, however, is generate a ton of waste and increase the cost of sterile compounding significantly .(1)

Current garbing practices are basically at the whim of groups like the United States Pharmacopeia (USP). The process by which USP creates these guidelines is not at all transparent. We have no idea what thought and/or research goes into their recommendations. Unfortunately, USP guidelines are frequently – almost universally – adopted in whole or part by other regulatory agencies like Boards of Pharmacy, Departments of Public Health, The Joint Commission (TJC), and so on. Few ever question the decisions because everyone is too busy trying to follow the rules and take care of patients to fight it.(2)

Over the past couple of weeks, organizations and regulatory agencies have been pulling back on the requirements for sterile compounding PPE, due in no small part to the disruption in the supply chain caused by COVID-19. It’s an evolving situation.

As we move through this crisis, I recommend the following:

  • Review your current PPE practices. Some folks are doing way more than is required. While noble on the surface, doing so is adding to the shortage and not necessarily benefiting anyone.  A prime example is pharmacies that use full PPE in anterooms.
  • Re-use PPE when allowed. See most recent USP recommendations here.
  • Do not place re-used PPE in plastic bags for safekeeping. I saw this recommendation somewhere and it makes no sense to me. People perspire in PPE, and zipping it up in a bag is akin to a makeshift incubator.
  • Sign up for USP, TJC, and local Board of Pharmacy email communications. Things are changing rapidly, at least they have been here in California. We’ve had to make several adjustments over the past 7-10 days, and I expect we’ll have to make even more in the coming weeks. It’s going to get weird.
  • Use common sense. Folks, pharmacists are highly trained, specialized professionals. Now is not the time to be averse to making judgement calls. It’s why we spent all those years in school and get paid the big bucks. Use your head. Be smart but be flexible.

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  1. It is not uncommon for large hospital pharmacies with busy cleanrooms to spend more than $10K per month on disposable PPE. Think about that the next time a hospital administrator complains about spending $3K on a “non-formulary” course of therapy
  2. Recently, a group successfully blocked the publication of new USP <797> guidelines. One of the reasons the group went after USP was due to lack of transparency in their process and failure to provide information when comments and requests were ignored.

Building a sterile compounding space in California – Regulatory Hurdles

For almost a year, I’ve been working as a ‘Pharmacy Project Manager’ on a large healthcare system project to bring all their pharmacy sterile compounding spaces — a.k.a. Cleanrooms, SCA’s, C-SCA’s, etc. — into compliance with USP General Chapters <797> and <800>. Some areas have been remodeled while others have simply been scrapped in favor of a completely new space.

The time on this project has been one of the highlights of my 20-plus year career. I’ve learned so much in such a short period. You think you know something until you have to start doing it day in and day out. It’s only then that you realize you know nothing. Here I am a year later and my knowledge base on sterile compounding has increased tenfold. It’s been a great experience.

One of the things that I learned early on in this position is that no pharmacy project in California is easy. There are several state and local agencies that have to be involved. And as one might expect, when government agencies get involved, the paperwork, time, money spent, and frustration can escalate quickly.

The process for remodeling or building a new sterile compounding area, at least in California, involves at least three agencies: the Office of Statewide Health Planning and Development (OSHPD), the California State Board of Pharmacy (BoP), and the California Department of Public Health (CDPH).

In a nutshell:

Office of Statewide Health Planning and Development (OSHPD): Part of the OSHPD mantra is to “ensure hospital buildings are safe”. They’re basically the organization that looks at your architectural and engineering plans and says yea or nay. My experience has mostly been nay on first glance followed by weeks of back and forth until all parties are satisfied. It’s an interesting process, to say the least. It’s also time-consuming.

OSHPD is a real stickler when it comes to anchoring equipment in place in case of an earthquake — noting that California has only had a few major quakes in the past few hundred years. A majority of our quakes are small and cause no damage. But don’t tell that to OSHPD. Their anchoring requirements are, shall we say robust; read that as overkill. The buildings around the anchored equipment will come crashing down long before the equipment will budge an inch. Just sayin’.

OSHPD is the first organization to sign off on a project. Once the plans are approved, a building permit may be issued and construction may begin. Once construction is complete, OSHPD inspects the area, and if everything meets code, they sign off and provide a Certificate of Occupancy (C of O) for the space.

I honestly don’t know a whole lot about OSHPD. The process is mostly handled by the architects, the project engineers, and the construction folks. I get informed with progress and sometimes provide snippets of information, but for me, the overall process is magic behind the curtains.

California State Board of Pharmacy (BoP): The BoP is responsible for ensuring that every pharmacy, or part of a pharmacy, conforms to the requirements set forth by the California Lawbook for Pharmacy. The BoP process starts with submission of an application, license sterile compounding or satellite pharmacy. The BoP reviews the document and either requests changes, which happens a lot, or approves the application and assigns an analyst. The analyst assigns an inspector to the project and a new set of back and forth begins. The inspector often asks for a lot of paperwork before their inspection: copy of sterile compounding PnP, testing and certification results for the room and hood, culture results, “QA” and competency results for staff, cleaning logs, etc. Once the inspector is satisfied with the paperwork — noting that each inspector is different and may ask for different things — they schedule a visit.

Assuming the BoP inspection goes smoothly, which is a hit and miss, the inspector will clear the site for licensing. Unfortunately, the inspector doesn’t actually license the space. All they do is notify the analyst assigned to your case that the space has been cleared for licensing. The actual license isn’t official until a new license number is assigned and posted to the BoP website. This can take anywhere from 2-6 weeks after the inspection. The BoP says “2 weeks” but I’ve found that to be inaccurate in almost all cases so far. The fastest I’ve had approval has been two weeks. The longest has been more than six weeks. If you haven’t heard from the BoP in two weeks, I recommend sending them a nudge, “hey, remember us?”.  It seems to help.

I recommend submitting your application to the BoP at least a couple of months before construction is complete.

California Department of Public Health (CDPH): If one were to assume that CDPH is a single organization, one would be only partly correct. For pharmacy projects, the organization is actually broken into multiple groups, each with its own set of requirements and approval processes for every single pharmacy sterile compounding project in California.

There’s the CDPH Central Application Unit (CAU), which works with each facility to ensure all necessary paperwork is in order: an HS Form 200 application form, along with a bunch of other paperwork like the OSHPD C of O and Form STD 850 Fire Safety Certificate. It’s quite a process. However, I’ve found that the CDPH CAU is easy to work with. They’re a friendly bunch that appears to want to help.

And there’s the CDPH Pharmaceutical Consultant Unit (PCU). As far as I can tell, the existence of the PCU in an official capacity is new. At least it feels new. The PCU requires its own laundry list of paperwork. Seriously, it’s a huge list of stuff.  The list includes the C of O for the space, even though the CAU requires it before they notify the PCU inspector; all sterile compounding PnP; temperature, pressure, and cleaning logs; a copy of the pharmacy plans, including HVAC system layout — even though this has already been approved by the engineers at OSHPD; test results for the room and hoods; employee competencies and QA testing; high-resolution photos of the space — even though CDPH PCU has no way to receive files this size and can’t use a file sharing service like Dropbox, Google Drive, or OneDrive from Microsoft.

Given my experience with the CDPH PCU, it’s difficult for me to understand their existence. They do almost exactly the same thing as the BoP. See above. It’s a duplication of efforts, to say the least. And in my humble opinion, the PCU doesn’t appear to provide any benefit to the overall health of the project. It doesn’t really matter as going through the PCU for approval of the space is required, so that’s what we do. Fortunately, the PCU inspectors are typically pretty easy to work with. They demand a lot but typically work with you to get it done.

The entire CDPH process is a bit convoluted. Once the CAU has everything they need for your new pharmacy sterile compounding area, i.e. they have all the paperwork, they notify the PCU that you’re clear for inspection. The PCU inspector contacts the facility via email or phone and works with them to schedule a field inspection. The inspector comes out, inspects the space, and if it’s good to go — almost never in my experience — they clear the space for use. However, the PCU clearance doesn’t mean you can use the space. The PCU inspector must first notify the local CDPH office with a “recommendation” to approve the space for use. The local office reviews the PCU inspectors report and if they agree with the inspector’s recommendation, which they always do, they notify the inspector of the approval. The inspector then notifies the facility that they’re good to go. Simple, right? Riiiight.

I recommend submitting your CAU application 4-6 months in advance of your construction completion date. I recommend contacting the PCU 2-3 months out. It’s better to be on their radar.

Final Thoughts

Building a new sterile compounding space is expensive, time-consuming, and disruptive. Even with the best planning, the regulatory processes in California are going to make you want to pull your hair out and scream. But there’s nothing you can do about it. I’ve found that being informed about the process is the best weapon in your arsenal, and can only help you in the long run. Get educated on the process. Reach out to all the agencies involved and find out what you have to do well in advance of your project. And don’t be afraid to reach out to the inspectors — BoP and CDPH PCU — because they’re there to help you.

Three concepts that create a lot of confusion: stability, beyond-use date, expiration

The differences between stability, beyond-use date (BUD), and expiration for compounded sterile preparations (CSPs) causes a lot of confusion. I’m not even certain that I fully understand their roles in day to day pharmacy operations. With that said, I think the key is for everyone to at least understand and agree that the BUD of a CSP is not the same as the expiration date.

Here’s how I understand it:

Stability is based on the chemical stability of the solute in solution, i.e. ingredients alone or in combination. This is what the Handbook on Injectable Drugs is all about, i.e. loss of drug potency/activity in solution.

Expiration date is defined by the FDA and identified by the product manufacturer.  Basically, it’s the shelf-life of the drug when properly stored. The expiration date no longer applies once the manufacture’s container is opened and the drug product is transferred to another container for dispensing or repackaging. Pharmacy uses “expiration date” loosely as we are not manufacturers. Most often I see pharmacies use expiration date in place of stability, i.e. the drug is good in solution for “this long”.

Beyond-use date (BUD) is assigned by the pharmacy for a CSP and is an arbitrary date/time found in USP <797> and adopted by many boards of pharmacy. BUD is based on sterility, stability. The BUD identifies the time by which a preparation – once mixed – must be used, i.e. “hung”. Once the CSP is hung on a patient, the BUD goes out the window and no longer applies. USP <797> does not address what to do with a CSP once it is hung on a patient. So something can have a BUD of 12-Hours, but be stable much longer. Pharmacies can extend BUDs, but only after independent sterility testing performed according to USP <71>, or in some cases when appropriate literature sources are used.

In summary, the BUD is not the expiration date, nor the stability of a preparation. Nurses must hang a CSP before the BUD is reached. The CSP can continue to hang on the patient until the “Expiration Date” is reached.

I would love to hear how facilities are dealing with these three concepts. Does your facility use a BUD and expiration on CSP labels?

Cool technology for pharmacy – Formulary Toolkit

Omnicell has been busy developing the IV automation and technology that they acquired from Aeysnt. Honestly, a couple of years ago I was ready to write off Aesynt’s presence in the IV room because of their tiny market share. This is when their current IV room products were still part of Health Robotics. With that said, the IV group has effectively reinvented themselves over the past couple of years and are doing some really neat stuff.

Two developments that I’m particularly excited about are REINVENT and Formulary Toolkit (FTK). I’ve written about REINVENT several times already, most recently just 6 days ago. I’ve mentioned FTK a couple of times in passing but have never really understood what it was, until now.

FTK

Aesynt website: “Said John Barickman, senior executive IV pharmacist consultant at Aesynt.  “With the Formulary Toolkit, we can now offer pharmacies data and services to better leverage automation technology and enable best practices in pharmacy like beyond use dating.”… Formulary Toolkit provides cost-effective access to cGMP quality gravity and drug stability data, in combination with established robust sterility protocols and testing services, that can be utilized to extend beyond use dates for compounded sterile preparations.”

Basically, Omnicell (previously Aesynt) has taken it upon themselves to do CSP stability testing for a select group of drugs. They do this to offer extended beyond use dating (BUD) for sterile compounds. Why would they do that? Sit back and I’ll tell you.

The BUD for a CSP identifies the time by which the preparation – once mixed – must be used before it is at risk for chemical degradation, contamination, and permeability of the packaging. In the absence of direct sterility and stability testing evidence that supports longer BUDs, USP <797> currently states that low-risk CSPs are good at controlled room temperature for 48 hours, at cold temperature (refrigerated) for 14 days, and frozen for 45 days. For medium-risk compounds, BUDs are 30 hours, 9 days, and 45 days, respectively.

Given appropriate stability and sterility testing, BUDs can be extended, giving a hospital the ability to plan further ahead, reduce waste, and better allocate resources. FTK takes care of the stability testing, giving pharmacies one important piece of the puzzle they need to create large batches with extended BUDs. Once extended BUDs have been established by laboratory testing, facilities have only to test batches for sterility.

So let’s say your pharmacy services several facilities in your healthcare system and uses a ton of vancomycin 1250 mg in 250 mL D5W [Baxter bags]. According to USP <797> you can get 14 days in the refrigerator or 48 hours at room temperature. However, what if stability studies demonstrated that the same CSPs were stable for 90 days at room temperature? You would be able to make significantly larger batches. Prior to using the batch, it would need to be quarantined while sterility testing was performed, which usually takes a couple of weeks. But, when the sample returned negative results, the batch could be used for the remainder of the 90 days, effectively extending the BUD by more than four-fold. This is such an advantage for pharmacies that must prepare frequent, large batches of specific drugs.

I don’t know what drugs have been tested for inclusion in FTK, but I’ve been told that data for several drugs in currently available and more are being added each quarter. Very cool.

JerryFahrni.com Podcast | Episode 12: Pharmacy IV room discussion with Ray Vrabel, PharmD

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

Jerry and Ray talk about the pharmacy IV room, specifically where we’ve been, where we’re at, and where we’re headed. Topics include workflow, the impact of USP <797> on pharmacy iv room operations, and thoughts on currently available iv workflow management system technologies.

You can learn more about Ray at his LinkedIn Profile here.

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.

Novel formulation of ethanol for glove decontamination to prevent Clostridium difficile contamination

Clostridium difficile is a major problem in hospitals across the U.S. According to the CDC, it is estimated that C. difficile caused almost half a million infections in the U.S. in 2011, and approximately 83,000 of the patients who developed C. difficile experienced at least one recurrence and 29,000 died within 30 days of the initial diagnosis.  Staggering numbers.

C. difficile is a nasty spore-forming bacteria that produces toxins. The main clinical symptoms of C. difficile infection include watery diarrhea, fever, nausea, abdominal pain, and loss of appetite. More serious infections can result in pseudomembranous colitis, perforations of the colon, and in extreme cases sepsis.

For the reasons cited above, I found this Pharmacy OneSource article quite interesting. According to the OneSource article: “A concise communication recently published in the Infection Control & Hospital Epidemiology (ICHE) journal provides effectiveness data on a novel formulation of ethanol used for glove decontamination to prevent Clostridium difficile (spores) hand contamination during glove removal… Test solutions included the novel, sporicidal ethanol formulation (70% ethanol adjusted to pH 1.3 with hydrochloric acid), as well as, 1:10 and 1:100 dilutions of sodium hypochlorite (bleach), and 70% ethanol with no pH adjustment/additives… [the] sporicidal ethanol formulation was effective in rapidly reducing C. difficile spores by approximately two logs, with a further reduction when applied as a wipe.” This was equivalent to 1:100 dilution of bleach solution.

While there are no studies that I’m aware of linking C. difficile infection to pharmacy cleanroom practices, such a novel anti-C. difficile solution has potential wide sweeping application throughout acute care facilities as well as long-term care facilities.

The abstract for the article cited in the OneSource piece can be found here states: “Decontamination of gloves before removal could reduce the risk for contamination of hands of personnel caring for patients with Clostridium difficile infection. We demonstrated that a novel sporicidal formulation of ethanol rapidly reduced C. difficile spores on gloved hands without adverse odor, respiratory irritation, or staining of clothing.” – Infect. Control Hosp. Epidemiol. 37.03 (2015): 337-339.

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.

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(1) Article 7.5, Section 4127(c)

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“.

USP soliciting comments for proposed changes to Chapter <797> Pharmaceutical Compounding—Sterile Preparations

The USP Compounding Expert Committee has published a Notice of Intent to Revise for General Chapter <797> Pharmaceutical Compounding—Sterile Preparations.

I knew this was coming. I’ve talked to several people this year that indicated that revisions to Chapter <797> were imminent, especially with the introduction of USP <800> Hazardous Drugs—Handling in Healthcare Settings.

According the USP notice:

The General Chapter has been under review since 2010 and has been significantly revised to clarify requirements, and reflect stakeholder feedback and learnings since the last revision became official in 2008.

Major revisions of the General Chapter include:

  1. Reorganization of existing sections and placement of procedural information in boxes
  2. Collapsing of the three compounded sterile preparation (CSP) microbial risk categories (e.g. low-, medium-, and high-risk) into two categories (Category 1 and 2) distinguished primarily by the conditions under which they are made and the time within which they are used.
  3. Removal of information on handling hazardous drugs and added cross-references to <800> Hazardous Drugs—Handling in Healthcare Settings
  4. Introduction of the terminology “in-use time” to refer to the time before which a conventionally manufactured product used to make a CSP must be used after it has been opened or punctured, or a CSP must be used after it has been opened or punctured.

Items #2 and #3 are significant.

Most hospitals do not currently make CSPs that fall into the microbial high-risk category. Altering these categories could have significant impact on acute care pharmacies.

The introduction of USP Chapter <800> Hazardous Drugs – Handling in Healthcare Settings will make any mention of hazardous drugs in the current Chapter <797> obsolete. I suspect that the Compounding Expert Committee will likely remove management of hazardous drugs from Chapter <797> and simply defer to USP <800>, which has yet to be published in anything other than draft form.

I will be spending the next week or so going through the proposed changes to better understand what the USP Committee is thinking. Remember, these revisions aren’t final.

Revisions to General Chapter <797> will be published for public comment in Pharmacopeial Forum (PF) 41(6) [Nov.–Dec. 2015] on November 2, 2015. You can view the proposed revisions with line numbers in advance of publication here [PDF].