I received an email yesterday from the International Journal of Pharmaceutical Compounding. The email contains a link to the IJPC’s Compounders’ Resource Directory. There’s a lot of good information on the list. It’s worth a look.
Both the IJPC and CompoundingToday.com are great resources for anyone doing extemporaneous (non-sterile) or sterile compounding.
Enjoy!
Here’s an interesting article from the January 13 issue of the Journal of Medical Internet Research (JMIR): Digital Pills To Measure Opioid Ingestion Patterns In Emergency Department Patients With Acute Fracture Pain: A Pilot Study (1)
A group of researchers out of Boston utilized digital pills (eTectRx, Newbury, FL, USA) to observe the ingestion patterns of oxycodone for patients discharged from the hospital following an acute extremity fracture.
Eighteen patients met inclusion criteria for the study, but only ten consented and were enrolled. Of the ten, eight had usable data. Not exactly a large number, but you gotta’ start somewhere.
Study drug was dispensed in capsule form. The digital pill was compounded with oxycodone tablets using a standard capsule-filling machine by the hospital’s investigational drug services pharmacy. Compounded digital pills were dispensed in blister packages.
When ingested, the gastric chloride ion gradient in the stomach activates the digital pill, transmitting a unique radiofrequency signal that is captured by a hip-worn receiver. The ingestion data is then transmitted to a cloud-based server where it can be viewed and analyzed. Because each digital pill emits a unique frequency, the system can record multiple simultaneous ingestion events, which is very cool.
It turns out that the digital pill did a pretty good job of recording the patient’s ingestion of their pain meds. It wasn’t perfect, and they had some technological issues along the way, but overall it results look promising. Imagine being able to see how your patients are taking their medication in real-time. You could even use the data coming from the digital pill to determine if a patient had ingested too many capsules at once.
The use of digital pills definitely has potential.
From the abstract:
Results: We recruited 10 study participants and recorded 96 ingestion events (87.3%, 96/110 accuracy). Study participants reported being able to operate all aspects of the digital pill system after their training. Two participants stopped using the digital pill, reporting they were in too much pain to focus on the novel technology. The digital pill system detected multiple simultaneous ingestion events by the digital pill system. Participants ingested a mean 8 (SD 5) digital pills during the study period and four participants continued on opioids at the end of the study period. After interacting with the digital pill system in the real world, participants found the system highly acceptable (80%, 8/10) and reported a willingness to continue to use a digital pill to improve medication adherence monitoring (90%, 9/10).
Conclusions: The digital pill is a feasible method to measure real-time opioid ingestion patterns in individuals with acute pain and to develop real-time interventions if opioid abuse is detected. Deploying digital pills is possible through the ED with a short instructional course. Patients who used the digital pill accepted the technology.
Pharmacy Practice News: “The National Institute for Occupational Safety and Health (NIOSH) held a meeting today in Cincinnati to discuss a universal closed-system drug-transfer device (CSTD) testing protocol, which is being developed… The new protocol will test both physical barrier systems, which block the intake of environmental contaminants or the unintended release of hazardous drugs into the environment; and air-cleaning systems, which clean or filter vapors to prevent the unintended release of drug or the intake of environmental contaminants… NIOSH released a draft test protocol last year to evaluate the efficacy of physical barrier–type CSTDs to see whether they prevented hazardous drugs from escaping the closed system. After hearing from the public and meeting with various stakeholders, NIOSH was asked to develop a new performance test protocol for air-cleaning CSTDs. Instead of developing a completely new protocol, NIOSH decided to develop a universal one that addressed both types of systems.”
NIOSH and the CDC game out with guns blazing back when USP <800> was drafted. Here’s the section on CSTDs from USP <800>:
5.4 Containment Supplemental Engineering Controls
Containment supplemental engineering controls, such as CSTDs, provide adjunct controls to offer an additional level of protection during compounding or administration. Some CSTDs have been shown to limit the potential of generating aerosols during compounding. However, there is no certainty that all CSTDs will perform adequately. Until a published universal performance standard for evaluation of CSTD containment is available, users should carefully evaluate the performance claims associated with available CSTDs based on independent, peer-reviewed studies and demonstrated containment reduction.
AÂ CSTDÂ must not be used as a substitute for a C-PEC when compounding. CSTDs should be used when compounding HDs when the dosage form allows. CSTDs must be used when administering antineoplastic HDs when the dosage form allows. CSTDs known to be physically or chemically incompatible with a specific HD must not be used for that HD.
Around the same time, the CDC and NIOSH released a “Vapor Containment Performance Protocol for Closed System Transfer Devices Used During Pharmacy Compounding and Administration of Hazardous Drugsâ€. The idea is admirable, but the testing method adopted by the protocol left some CSTD manufacturers on the outside looking in, and they let the CDC know about it. Feel free to drop by the protocol comment site for clarification.
Apparently the comments made an impact because NIOSH is going back to the drawing board to try and come up with a universal protocol to meet the testing needs for all CSTD systems. However, one has to wonder if the damage is already done. For the past several months pharmacies have been making decisions on which CSTD to use based on information in the draft vapor containment protocol. Right or wrong, that’s the truth of the matter. I have to believe that some of the companies in this space have been irreparably harmed. Only time will tell.
Management of controlled substances(1) inside acute care pharmacies is a mess. It’s difficult for me to stress how utterly disappointed I am by this area of pharmacy technology.
I haven’t been in a pharmacy in years that wasn’t using technology to manage these drugs. This is likely due to the amount of fear and regulation swirling around controlled substances. These drugs have the highest level of control and are more regulated than any other drug class; at least until USP <800> goes live. The paranoia around these medications is crazy. The man hours dedicated to their management is obscene.
Based on my observations, the technology is outdated, difficult to use, and has failed to improve the process in any appreciable way. It remains unclear to me what advantage these systems offer. I don’t think it would be difficult for someone to argue in favor of ditching the technology in lieu of replacing it with two people locked inside a room using pen and paper. Crud, it might even be more efficient.
Consider that in a majority of instances the inventory management system used to manage controlled substances is separate from the system used for other inventory, and almost never tied directly to the EHR. Yes, it means you have to maintain a separate database for one area within the pharmacy.
Also consider that at least one of the major players in this area cannot handle partial doses, i.e. half-tablets or increments of mL’s. That’s right, software designed to keep detailed records for controlled medications chokes on something as simple as 7.5 mL.
This is an area of the pharmacy that needs an enema. Someone out there must have a better way. If you have any ideas, please give them up.
And for the companies playing in this space, you really need to do a better job. Go sit in a pharmacy for a day or two and observe how utterly terrible these systems are to use.
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Two things happened to me recently that have pushed this question to the front of my mind.
The first is by way of some comments that were left in response to something I wrote in June about Google’s new symptom search. The comment is as follows:
“...I have to question your closing statement: The idea of such a vast amount of knowledge at one’s fingertips is mind boggling, to say the least. Google, like any reference, has “informationâ€, but I’m not sure if I would classify it as a “vast amount of knowledgeâ€. Actually, knowledge on the part of the reader is what is required to make sense of the information that a source like this provides. The ability to interpret drug literatures only comes with education, training, and experience…”
The second item comes from a Reddit thread that I got involved with a few days ago. In the thread a user asks whether or not a pharmacist could be replaced “by a computer†in another 20 years. I argued that it could certainly happen. Someone countered by saying that it couldn’t happen because “the evaluation side, the interpretation of a patient, taking it’s [sic] history into account†couldn’t be done by decision-making software.
Depending on which side of the fence you’re on, there is potential for some good discussion here.
As I see it, information by itself holds little value. Having the skills to apply information to a given situation, i.e. “having knowledgeâ€* makes all the difference in the world. Many think that it is this that makes humans indispensable in certain roles, like pharmacists. However, don’t be too quick to dismiss the ability of artificial intelligence (AI) and machine learning (ML) to mimic the actions of a human, especially in healthcare. Both AI and ML are powerful tools that can be used to appropriately apply information to any given situation. If a piece of software is able to use ML and AI to apply information to a situation based on past experience, doesn’t this become “knowledgeâ€? I think it does.
This is what pharmacists do throughout their career – take what they’ve learned, add it to what they’ve experienced, and apply it to a given situation – and why seasoned veterans are so valuable. It’s not that they’re smarter than their younger counterparts; it’s that they’ve been around longer and seen more. The knowledge gained by veteran pharmacists is often the difference between making average decisions and making great decisions. As pharmacists practice, they gain more knowledge. As time goes by it becomes increasingly rare to see new situations. I’m sure that computers can take information and combine it with previous actions and outcomes to make decisions. They do it all the time.
Not all knowledge requires depth of logic and “freedom of thoughtâ€. Take for example a pharmacist that gains knowledge by reading through a new set of treatment guidelines, or a journal article, or by attending a conference lecture. After digesting the information – use drug x in this situation – the pharmacist is ready to apply it. This is one of the things that make pharmacists better as clinicians over time, i.e. learning new things from others. Can’t a computer use the same information and be given parameters from which to apply it? Sure. How is that different from a human pharmacist? On the surface it’s not.
So while I understand the desire for pharmacists to push back on the idea of being taken over by computers, I fundamentally disagree. I believe that 80% of what pharmacists do right now could be successfully emulated by a combination of technologies. Decisions made by pharmacists rarely require some special power of observation. Most are actually pretty cut and dry. What about those times that require a judgement call? That’s the other 20%. And while I think you need a pharmacist to make those calls today, I don’t think it will be long before technology can do the same thing. After all, most judgment calls are simply something learned plus experience. Computers may not be able to think on their own, but they can certainly take information, search for a previous encounter, and “make a decisionâ€.
Obviously this is just my opinion, take it for what it’s worth.
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*one definition of knowledge – “facts, information, and skills acquired by a person through experience or education; the theoretical or practical understanding of a subject.â€
USP <800> has an entire section dedicated to deactivation, decontamination, cleaning, and disinfecting areas that are used for compounding sterile hazardous drugs (HDs).
The chapter calls for:
Deactivation – Renders the compound inert or inactive. Residue from deactivation must be removed through decontamination (see below). There is no single method for deactivating all known compounds.
Decontamination – Inactivating, neutralizing, or physically removing HD residue from non-disposable surfaces via wipes, pads or towels. This includes work surfaces and under work trays where residue may collect.
Cleaning – Process to remove contaminants – organic and inorganic material – from objects and surfaces using water, detergents, surfactants, solvents, and/or other chemicals. Cleaning may not be performed while compounding activities are occurring.
Disinfection – Process of inhibiting or destroying microorganisms. Required for surfaces where sterile compounding occurs.
Most of the above is common sense. While it may seem complicated, most pharmacies will simply purchase kits designed to walk them through the process. An example of a kit used to meet USP <800> requirements is WipeDown 1-2-3 by Valtek Associates. I’m sure there are others as well.
The WipeDown 1-2-3 product description can be seen below. Notice that the kit contains numbered packets designed to walk you through the process, i.e. Packet #1 – deactivation, Packet #2 – decontamination, Packet #3 – disinfecting/cleaning. Pretty straightforward.
WipeDown 1-2-3 is a sterile 3 step application wipe kit, that when used in sequence, provides deactivation, decontamination, and disinfection/cleaning of sterile compounding surfaces from most hazardous drugs. WipeDown 1-2-3 satisfies both USP compounding sterile preparations and USP hazardous drugs – handling in healthcare settings.
Each Sterile WipeDown 1-2-3 kit includes:
- Packet #1 – HYPO-CHLOR®, 5.25% Sodium Hypochlorite for deactivation
- Packet #2 – THIO-WIPE, 2% USP Thiosulfate for decontamination
- Packet #3 – ALCOH-WIPE®, 70% USP Isopropyl Alcohol for disinfecting/cleaning
Medgadget: “A collaboration between researchers at the University of British Columbia and Paul Scherrer Institut in Switzerland has developed a microneedle device for drug monitoring. The device is in a form of a patch that’s stuck onto the skin, painlessly pushing microneedles through to sample the interstitial fluid…The proof-of-concept device reported by the team was used to measure the concentration of vancomycin.”
This is something that has been sorely needed for a long time. As a pharmacist, I can confidently state that we spend entirely too much time looking at drug levels that are within normal limits versus evaluating those that are not. It would seem much more efficient, at least in the acute care environment, to ignore “normal” levels and spend our time investigating those that are out of whack.
In the outpatient environment this makes even more sense as a patient safety measure. Imagine never again having a patient urgently admitted to the hospital for a drug level that’s way too high. Think of all the medications that require at least intermittent drug levels: carbamazepine, phenytoin, digoxin, tacrolimus, and so on.
Side note, my mother was taking tacrolimus around the time of her liver transplant. An EHR charting error occurred that resulted in her receiving 10 mg orally twice a day instead of 1 mg orally twice a day; yep, a 10-fold error. True story. Almost killed her. The small-town hospital where she lived didn’t recognize the symptoms and failed to get a drug level when she was admitted for “dehydration”. Several days of pleading with physicians and calls to UCSF resulted in a level being drawn. It was off the charts. She was subsequently transferred to UCSF where she spent the next six weeks in the ICU. The entire ordeal could have been avoided with real-time drug monitoring. Just sayin’.
I recall being really excited about sensor-enabled asthma inhalers several years ago. I even remember giving a presentation in 2013 on “the future of pharmacy†that included two such products: Asthmapolis and GeckoCap. Each was an add-on device for existing inhalers. They were marketed as tools for improving medication adherence, and by default helpful in controlling patient’s asthma symptoms. Each had a very different approach but were both pretty cool in their own way.
Asthmapolis is still around, as far as I can tell, but at some point, the product was rebranded as the Propeller Sensor by Propeller Health. The only reason I know this is because earlier this year the Propeller Sensor received FDA 540(k) clearance. I always thought the approach used by Asthmapolis was interesting because the product utilized crowed-sourced data to generate “Asthma risk maps†to help keep patients with asthma informed about potential hot zones in and around their area. It appears as though not much has changed. While the Propeller Health website doesn’t offer many details, a quick search of the web generated several articles that lead me to believe the mission remains the same. I’m still impressed with the Propeller Sensor and would love to see it in action sometime. It seems like it would be well suited for use by ambulatory care pharmacists.
The other product, a little doohickey known as GeckoCap was a glowing “smart cap†that used a blinking light and gamification to remind patients when to use their inhalers. Data collected by the device was transmitted to a database via Bluetooth connection where family members and physicians could access it. I thought the use of gamification was rather clever, especially for kids. Parents could set goals with accompanying rewards to encourage kids to remain compliant. In this day and age, that made sense to me.
Similar to Asthmapolis, it appears that at some point GeckoCap became CareTRx [pronounced care-tracks]. However, it doesn’t appear that the product is actively being developed at this time. The last few reviews on the Google Play Store included complaints about server issues, and those were from December 2015. Based on information at the CareTRx website, the company was acquired by Teva in September of 2015. I’m not sure what that means. I don’t know if the product is dead or alive.
I wonder why these products never took off? Seems like these little devices would fit right into the up and coming Internet-Of-Things era.
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.
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.â€â€¦ 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.â€
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.
Interesting timing on this article at Healthcare IT News: “With an eye on improving safety, increasing compliance and reducing waste, an increasing number of hospitals and health systems are looking to insource and automate their IV compounding processes… Campbell said that the transition to robotic sterile compounding has resulted in a cost savings of $100,000…At the core of the technology is Omnicell’s REINVENT – Registry for Intravenous Technology in Pharmacy – global, multi-site data registry designed to collect compounded sterile preparation data from hospitals and health systems for evaluation, analysis and insight.”
I spent some time earlier this week speaking with Omnicell about their IV room automation and technology, including REINVENT. I’ve written about REINVENT before. Since that time, Omnicell has made big strides in connecting customers and collecting sterile compounding data.
It is my belief that most companies in this space fail to understand the value of all the data floating around in pharmacies. There is so much untapped potential there. Few vendors have given serious consideration to how best to deal with it, much less create a product that brings value to their customers. I’m pretty stoked about what Omnicell is doing with REINVENT and hope that other vendors will follow their lead. The future of pharmacies is in the data.