Where to get information on compounding sterile preparations

Someone asked me the other day where they could read up on what’s going on in the world of pharmacy sterile compounding. It’s a good question. The simple answer is to get your hands on a copy of the USP Compounding Compendium and read it over and over again. That’s where I started. Unfortunately, that will make you about $150 lighter in the wallet. Not to mention that it’s not the most entertaining of documents.

ASHP offers several training courses that include written material as well as video. I’ve gone through many of them myself. They’re good, but expensive. You can see a list of them here.

ASHP also offers a Sterile Compounding Resource Center. Lots of good content there, especially in the Policies, Best Practices, and Guidelines section. Some of the material may require you to be an active ASHP member, but I believe some (much?) of the content is free.

I’ve found Pharmacy Practice News and Pharmacy Purchasing & Products to have lots of good, timely content pertaining to sterile compounding. The best part about these two publications is that they provide free access after a one-time registration process.

If you’re just looking for general reading material, a Google search for sterile compounding, compounded sterile preparations (CSPs), primary engineering controls, beyond-use dating (BUD), USP <797>, or pharmacy compounding will give you more than you can handle.

Anyone else have any recommendations for where to find information on sterile compounding? If you do, feel free to leave a comment below.

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“.

JerryFahrni.com Podcast | Episode 6: Stability of CSPs in Syringes

Jerry talks about the problem with storing medications in plastic syringes and potency loss. Recently the FDA notified ASHP that no plastic syringe is approved for use as a final storage device. Jerry discusses the issue and how it will impact pharmacies in the near future.

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

Articles discussed in podcast:
Initial Reaction to FDA Stance on Syringes As Standalone Storage Container [JerryFahrni.com]
No Syringe Is Approved as a Standalone Storage Container, FDA Says [ASHP]
ISMP Comments On BD Syringe Potency Issue [ISMP]
Compounded or Repackaged Drugs Stored in Becton-Dickinson Syringes: FDA Expands Warning [FDA Alerts]

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

Saturday morning coffee [October 10 2015]

“Those who cannot change their minds cannot change anything.” ― George Bernard Shaw …you people know who you are.

So much happens each and every week, and it’s hard to keep up sometimes. Here are some of the tabs that are open in my browser this morning along with some random thoughts…

MUG_SMC

As predicted, The Martian was #1 at the box office last weekend, pulling in a just over $54 million in its opening weekend. It’s a good movie. Highly recommended. I expect The Martian to hold the #1 spot for a bit longer. Who’s going to challenge it, Pan?

Speaking of movies, my younger brother came up to Fresno last Sunday and took me to see Everest. The movie recreates one of the worst climbing disasters in history. I don’t usually go in for movies like that, but Everest was really quite good. Another film I would recommend.

I’ve always been a drip coffee guy, probably because that’s how I got started drinking coffee. I’ve tried various methods – pour overs, coffee press, running by Dutch Brothers twice a day – but I always come back to drip. Recently my tried and true Mr. Coffee Coffeemaker took a turn for the worst and I had to replace it. Instead of simply getting another Mr. Coffee, I wanted to try something different. I did a little online research and finally decided on a Bonavita 8-Cup Original Coffee Brewer. While the Bonavita is still makes coffee via “drip”, the water comes down onto the grounds in a sort of showerhead fashion, and the “pot” is a carafe that keeps the coffee warm for several hours. There is no warmer under the carafe. It works very well. I’m quite satisfied with the coffee it brews. The only thing that’s a bit of a bummer is that you can’t pull the carafe out before it’s finished brewing when you just can’t wait five minutes for it to finish. I used to grab the carafe on my old Mr. Coffee as soon as I had enough black gold to warrant a cup. The price we pay for good coffee.

Microsoft had an epic event this week in New York. The company introduced some of the most exciting new products that I’ve seen in years. The company took their already class-leading line of Surface machines and introduced the new and improved Surface Pro 4. The Surface Pro 4 has updated internals, a slightly larger display, improved pen technology with a better inking experience, and a better detachable keyboard. And the best thing of all is that you can custom configure the device to your liking at the Microsoft Surface site. But that’s not all. Microsoft also introduced what I think is the most innovative piece of hardware that’s come along in a while, the Surface Book. The Surface Book offers a crazy new design, making it both a complete laptop and a full-fledged tablet. It also gives users the ability to configure the Surface Book to rival any 13-inch high-end laptop on the market. It’s what a modern ultrabook-tablet should be. Surface Book is quite literally my idea of the perfect machine torn from my brain and turned into reality. It’s the most excited I think I’ve ever been for a piece of new consumer technology. It’s beautiful, and I must have one.

Here’s an interesting website: http://easypcpicker.com/. “Easy PC Picker exists to simplify the process of buying a new computer. We ask you three simple questions (price, operating system, and features) and then provide a recommendation hand-picked by our staff of experts.” I played with it a little bit. It’s not perfect, but it kicks out some solid choices for anyone looking for a new machine.

Who would have thought that Velcro could be dangerous? I’ve managed to get a few nicks and cuts on my hands from unstrapping and re-strapping my leg brace several hundred times over the past few weeks. I’m theorizing that the little hooks on one side of the Velcro strap are able to grab tiny pieces of skin that are loose. And when they grab hold, they don’t let go.

Speaking of Velcro, it “is the brainchild of Georges de Mestral, a Swiss engineer who, in 1941 went for a walk in the woods and wondered if the burrs that clung to his trousers — and dog — could be turned into something useful. After nearly eight years of research (apparently it’s not so easy to make a synthetic burr), de Mestral successfully reproduced the natural attachment with two strips of fabric, one with thousands of tiny hooks and another with thousands of tiny loops. He named his invention Velcro, a combination of the words “velvet” and “crochet,” and formally patented it in 1955. Though the first Velcro was made out of cotton, de Mestral soon discovered that nylon worked best because it didn’t wear with use.” And the moral of the story? Take time to go for a walk in the woods. (source: Time)

Have I ever told you how awesome 3D printing is? There’s a lab at the University of California San Francisco (UCSF) –  <cough>… my alma mater – that’s using living cells as the substrate to 3D print human tissue. “Zev Gartner, PhD, has focused on the next best thing: His lab is building fully functioning 3-D human tissue, cell by cell. It sounds straight out of a Frankenstein novel, but Gartner is working to grow the milk-producing tissues of the human breast to create a living, working model of the human mammary gland that grows, ages and responds to hormone signals just like the real thing. This means growing the ducts, arteries and connective tissue in the same environment.” Crazy.

How long before we all have 3D printers in our houses to print everything from our breakfast cereal to a new spray nozzle for our hose? It’s not as far off as one would think. It could even happen before I decide to checkout for good.

This week the FDA told ASHP that it has “not cleared or approved any syringes for stand-alone use as ‘closed container systems.’” Oh boy, that’s a biggie. You can read my initial thoughts about the announcement here, but I think it’s going to cause some problems for pharmacies.

Variety: “Consumers are now using mobile phones more often to search Google than desktop PCs…“We are getting over 100 billion searches every month,” Singhal said. Mobile overtook the desktop as the number one source of traffic this summer, he said.” – I talked about this a few years ago during a presentation I gave at a SoCal HIMSS Meeting. Those things in your pocket aren’t phones, they’re computers. My thought is that there has to be a way for pharmacy to leverage that knowledge to improve patient care. Really hasn’t happened yet.

You really should stop whining about your commute. Take a look at what happens when people return from vacation in China. Dude, that’s some traffic right there.

And just like that the Cardinals broke my heart. I said last week that the Rams defense was good, and they gave Palmer fits all afternoon. The Cardinals play the Lions tomorrow. I think it’s a winnable game, but the Lions have nothing to lose, which makes them dangerous. Expect the Cardinals secondary to have their hands full with the Lions long-ball.

Ugh, the Bruins took one in the shorts last Saturday night. Hats off to Arizona State, they punched UCLA in the throat. No game for the boys in baby blue this weekend. Good thing, as they have Stanford up next on the schedule. They’ve had trouble with the Stanford running attack and defense over the past few years. Fingers crossed.

Have a great weekend everyone.

Initial reaction to FDA stance on syringes as standalone storage container

This morning I woke to the news that No Syringe Is Approved as a Standalone Storage Container, FDA Says. This I’m sure is in response to the recent issue with BD syringes and drug stability. I need to think about this more, but my gut reaction is that this is huge and will have a significant impact on many acute care pharmacy practices across the country.

There are three factors to consider when making and dispensing compounded sterile products (CSPs): accuracy, sterility, and stability.

Accuracy. Self-explanatory. When you make a CSP you want it to be as accurate as possible. This is where I believe automation and technology come into the equation. My thoughts on the subject can be found in many essays/articles published on this site.

Sterility is covered ad nauseam by USP General Chapter <797>. CSPs should be free of microbial contamination. This, of course, is for the safety of patients receiving treatment with CSPs. If you have any questions regarding how long something can be stored following compounding, and still be considered “sterile” then you should look no further than the beyond-use dating (BUD) guidelines found in <797>.

Stability. When you store something in a container, i.e. a syringe, bag, bottle, etc. you want the drug to remain active for as long as necessary to administer to the patient. We know that some drugs are sensitive to light, temperature, type of storage device, etc. However, pharmacy has long used syringes as a method of distribution, and as long as the drug was considered unaffected by light and temperature, not much consideration was given to stability.(1) This is a holdover from the days when we, i.e. pharmacy used to draw everything up in glass syringes. Glass was an awesome storage medium, but we didn’t really change out practice when glass syringes became too expensive to be practical and we went to plastic. While addressed in USP General Chapter <797>, stability is not given the same detailed coverage as sterility. USP <797> was never meant to address stability in great detail.

Recently I’ve seen an upward trend in pre-drawn syringes. I’ve spent the better part of the last three months immerging myself in what goes on with medication distribution and use in the O.R. That is to say I’ve been educating myself on processes and paradigms of how anesthesiologists and pharmacy work together to ensure safe, accurate and responsible medication use during surgery.

One of the major trends I found in O.R.’s was the use of pre-drawn syringes. Pharmacy likes them because it gives them more control over drug usage and waste, and anesthesiologists like them because they don’t have to draw medications from vials prior to administration. Anesthesiologists are more concerned with monitoring the patient then they are with having to deal with medication labeling, etc.; and rightly so.

This desire to supply anesthesiologists with pre-drawn syringes has created an interesting side effect in CSP automation – there is a renewed interested in CSP robots in the clean room. Robots are good at batch production. Pulling several hundred syringes filled with the same drug is an ideal use for a compounding robot.

This of course, doesn’t include pediatric facilities that use pre-drawn syringes to stock their shelves to meet the needs of their patient population. I remember when I was a pediatric pharmacist back in the early 2000’s. We pulled thousands of syringes each and every day to replenish stock not only on our shelves in the pharmacy, but to place in ADCs for easy access to medication for nurses and physicians.

Some pharmacies will use third party vendors like PharMEDium for their pre-drawn syringes. I bet companies like PharMEDium already have data on the stability of drugs stored in syringes. Will they share this information with the rest of the pharmacy world? My gut reaction is that they won’t. By sharing  information they’re basically cannibalizing their own sales. What’s this do for them? Uptake of customers and bigger sales in the immediate future. It’ll be interesting to see how they handle it. Not to mention potential liability snafus.

Like I mentioned above, I need to think on this more deeply. However, at this moment I’m thinking that the FDA’s stance on syringes as stand-alone storage devices is going to create a lot of headaches for pharmacies across the country over the next several weeks. It’ll be interesting to see how organizations like ISMP, ASHP, USP, etc. respond to the FDA’s statement.

Grab some popcorn folks, this should be good.

——-

  1. There’s much more to this statement, but for the sake of brevity let’s just leave it at that.

Saturday morning coffee [October 3 2015]

“If someone is able to show me that what I think or do is not right, I will happily change, for I seek the truth, by which no one was ever truly harmed. It is the person who continues in his self-deception and ignorance who is harmed.” ― Marcus Aurelius

The mug below was given to me by my awesome wife and daughter. They went out to run an errand a few weeks ago and saw this mug. Apparently they decided that I really need it. They were right. It’s a pretty cool mug.

MUG_DarthVader

Hotel Transylvania 2 was #1 at the box office last weekend, pulling down nearly $50 million in its opening weekend. The first one was good, and I suspect this one is too. Sometimes I wish I still had little ones running around the house. It would give me an excuse to see movies like Hotel Transylvania 2. Don’t expect it to stay at #1, however. The Martian will likely take that spot this weekend. My wife and I saw The Martian yesterday. Besides some over-the-top corniness right near the end, it was a very good movie. Highly recommended.

Did you know that Finland is the top coffee consuming nation in the world? It’s true. Those pesky Finns drink a national average of 2.64 cups of java per day. According to WorldAtlas.com “the most popular coffees in Finland are very light roasts, much lighter than anywhere else in the world”. My kind of coffee drinkers.

I really need to try this, putting butane in Coke. Seems like a decent afterschool activity to me.

The ‘c’ key on my Yoga 2 Pro is giving me problems. Sometimes I’ll have to hit it 2 or 3 times to get it to work. It’s really starting to piss me off. You don’t realize how often you need a ‘c’ until you look up at a document you’ve been working on and it looks like someone wend crazy with a red pen underlining misspelled words. I’ve really lost faith in Lenovo with this machine.

There’s been another mass shooting, this time at Umpqua Community College in southern Oregon. Ten people were killed and another seven injured Thursday when a 26-year-old gunman opened fire in a classroom at the community college. Very sad. It gets harder and harder each time something like this happens for me to defend my pro gun position. There’s just no place for this kind of thing in our society. I don’t have an answer, but it’s obvious that what we’re doing isn’t working.

Reuters: “A new electronic drug capsule engineered to deliver medications directly to the colon could potentially offer a more effective and cheaper option for treating people with gastrointestinal conditions, according to researchers at Purdue University in Indiana. The device is comprised of two parts, one carrying a drug payload and the other housing electronics designed on the same principles used to trigger a torpedo.” – The capsule contains a magnetic trigger that separates the capsule and releases the medication. I worked on a project team that was researching something like this when I was an undergrad in chemistry. Very cool stuff.

Speaking of cool developments, Nanowerk News is reporting that “[r]esearchers have for the first time developed a technique that coats anticancer drugs in membranes made from a patient’s own platelets, allowing the drugs to last longer in the body and attack both primary cancer tumors and the circulating tumor cells that can cause a cancer to metastasize. The work was tested successfully in an animal model.” Anything that can be done to improve the targeting of cancer cells without wrecking healthy cells is a good thing. Nanotechnology rocks.

Are you a visual note taker? If so, you should drop by this site and check out 50+ Awesome Resources to Create Visual Notes, Graphic Recordings, & Sketchnotes. I desperately want to learn how to take visual notes. I’ve tried it a few times, but can’t seem to make it work. I envy the people that can do this.

visual note-taking

Google announced some awesome new hardware this week: two new Nexus phones – the Nexus 6P and Nexus 5x, the Pixel C Android tablet, a new Chromecast, and Chromecast Audio. The Nexus 6P is a spectacular device, and the Pixel C will surely become the poster child for flagship Android tablets. The announcement of the Nexus 6P has muddied the waters for me as I was just about to pull the trigger on a Samsung Galaxy Note 5. I was looking at the Moto X Pure Edition, but decided that I really wanted a Note 5 for the camera, active digitizer, and Samsung Pay. The Nexus 6P lacks the active digitizer and Samsung Pay, but offers similar camera performance and a pure Android experience. Tough choice. Actually, now that I write it out, I think I’ll stick with the Note 5….or not. Ugh.

With the introduction of the Nexus 6P, Android now has the top six best mobile cameras on the market. This according to the DxOMark website. The top ten, starting at the top: Sony Xperia Z5, Samsung S6 Edge, Google Nexus 6P, LG G4, Samsung Note 4, Moto X Style, Sony Xperia Z3+, Apple iPhone 6Plus, Apple iPhone 6, Samsung Galaxy S5. Note that the Galaxy S6 and Note 5 have the same camera as the S6 Edge, which puts them in the same slot. My wife and oldest daughter have the LG G4, while my youngest daughter has the Galaxy S6. I can tell you that the images captured by those devices are spectacular. My S5 takes pretty good shots, and both the G4 and S6 put it to shame. Smartphones have become the new point-and-shoot camera of this generation.

Gizmodo: “Tom Scott has an excellent video explaining the basic physics behind the Falkirk Wheel, a rotating boat lift in not-so-sunny Scotland. It enables boats to travel between two canals, one of which runs 80 feet higher than the other.” – I remember sitting with my mom one evening a little more than a year ago and watching a special on the Falkirk Wheel. Very cool engineering.

Due to a recent mishap I’ve had to make extensive use of our current healthcare system. I’m amazed that the system works at all. To say that the system is disjointed and full of incompetence would be putting it kindly. Actually, calling it a system is probably a misnomer because that assumes that things are connected in some logical fashion. They are not. And now that the bills have started rolling in, I find it a confusing mess of “billers”, adjustments, and insurance company EOBs. Let me give you just one example of the craziness that is our healthcare system. During an ED visit I had several X-Rays and CTs taken. Fast forward several days when I had to see an orthopedic surgeon in his office. I had to contact the hospital, request that the studies be placed on a CD – seriously, a CD – and hand carried them to my appointment. Hard to imagine in this day and age that those images couldn’t be stored “in the cloud” and simply accessed at will. Here’s the kicker. When I arrived for the appointment, the orthopedic surgeon ordered a completely new set of X-Rays because he “likes to get his own images”. Then he sat down to view the images on my hand-carried CD and couldn’t open it using his office-based EHR system. It wouldn’t read the image type. Zing! And yes, I received bills for both the ED and office taken X-Rays. I have other crazy stories from the past several weeks, but won’t bore you with the details. Suffice it to say, the current healthcare model sucks.

Harvard Business Review: “…findings from our research using six years of data from nearly 3,000 acute-care hospitals suggest that it is the communication between caregivers and patients that has the largest impact on reducing readmissions. In fact, the results indicate that a hospital would, on average, reduce its readmission rate by 5% if it were to prioritize communication with the patients in addition to complying with evidence-based standards of care.” – Huh, imagine that. It appears that communication is important. I found communication lacking when caring for my mom. Some facilities, like UCSF did a good job of communicating with both my mom and the family. Other facilities, like the two we used in the Central Valley, failed miserably at communicating information. It made a tremendous difference in her care.

The Samsung Gear S2 smartwatch went on sale yesterday. Love that watch. If I go with the Note 5 mentioned above, I’ll likely pair it up with the Gear S2. Below is a quick review by Flossy Carter. Love this dude’s reviews.

Football season is well under way and it’s been awesome. There have already been some upsets among the college ranks…cough, Ole Miss. UCLA is playing well and look good to take the PAC-12 South. They play Arizona State today. Look for them to take care of business early and win that one. The NFL is chugging along. Nothing really stands out there besides the quarterback shuffle that’s taken place secondary to injuries. My Cardinals look great. Unfortunately, they’ve done this to me before, i.e. started out strong only to finish on life support. I’m holding my giddiness until around week 10. They play the Rams on Sunday. It’s a very winnable game, but those division games can be a bugger. Not to mention that the Rams have an angry pass rush, and Carson Palmer is getting hit like a pinata this year. They really need to keep that dude upright if they have any hope of making a playoff run.

Have a great weekend everyone.

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].