Ten Questions and Answers on CSTDs With Fred Massoomi, PharmD, FASHP

Pharmacy Times Health Systems Edition, November 2016, Volume 5, Issue 6

Firouzan “Fred” Massoomi, PharmD, FASHP, is the pharmacy operations coordinator for Nebraska Methodist Hospital Pharmacy.

Firouzan “Fred” Massoomi, PharmD, FASHP, is the pharmacy operations coordinator for Nebraska Methodist Hospital Pharmacy. He has lectured nationally about implementation strategies for USP <797> compliance, hazardous drug management, proper disposal of hazardous drug waste, and has over 14 years of experience in testing and using closed-system transfer devices (CSTDs). Specialty Pharmacy Times interviewed Dr Massoomi for his expert perspectives on the growing importance and use of CSTD systems.

1. What are CSTDs and what does CSTD use mean practically for a specialty pharmacist or pharmacists practicing in a hospital setting?

Closed System Drug Transfer devices are highly specialized, designed drug compounding and drug administration devices that are uniquely designed to protect health care providers and patients from the exposure to hazardous drugs. CSTDs were first introduced to the US in 1998 and formally defined by NIOSH in 2004 as “a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system (http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf).” There are 2 key points to this definition, and also to what these devices are touted to be.

One is that a CSTD does not allow anything to come into the system once it is fully engaged and fully closed, meaning that there is no bacteria or particulate matter associated with compounding, either by accident or by accidental contact with high-risk sterility points. It does not allow bacteria or particulate matter to enter the system, and more importantly, as we are doing the manipulation step of either compounding or administration of the product, the CSTD does not allow any of the product within the system to escape, be it in a vapor form, or spray or droplet form—“nothing in nothing out.”

2. Several CSTDs are available, including PhaSeal, Spiros, Texium, On-Guard/Tevadaptor, ChemoClave, Equashield/Equashield II, ChemoLock, Halo and Vialshield. Which of these are you most familiar with and what are some of the favorable and unfavorable characteristics of different devices?

We have done research on all available devices. We have also investigated a newer product on the market (Halo) that is currently undergoing trials as far as validating its role.

The Nebraska Methodist Hospital Hazardous Drug team has had very extensive experience working with all of these products and we have had all of them in here at some point, either in a research format or in a utilization format. Just recently, the Nebraska Methodist Hospital Hazardous Drug group repeated the proposed NIOSH Vapor Containment Performance Protocol for Closed System Transfer Devices Used During Pharmacy Compounding and Administration of Hazardous Drugs, Picture.

We learned a great deal about all of the devices by performing this test. There are 3 broad categories I could place these devices into. The first is full containment utilizing a diaphragm-based system, similar to the systems used by PhaSeal (the innovator product), ChemoLock (a newer product from ICU medical), Vialshield, and Halo.

Basically, you have a diaphragm that collects both vapors and any sprays that may occur through equalization of pressure within the system. The second grouping I would broadly classify as compartmentalized-based devices, meaning that there is no external additional piece to the system. The ability to contain and equalize pressure is built within the system. A total of 3 devices use some variation of this process.

Equashield I/II compartmentalizes the vapor behind the barrel head of a highly engineered syringe and transfers the vapor in between the system and the vial, and does the equalization of pressure using the sealed back portion of the syringe so that vapors and any sprays do not come out of the system. Another example of compartmentalization is the older device, ChemoClave, which uses the Genie device that allows for compartmentalization and equalization of pressure within the vial of the drug.

With this device, a balloon inflates within vial to help equalize the pressure between the syringe and the vial itself. One CSTD that did not make it to market that used the compartmentalization process was SureConnect, which was originated by Baxa and is now owned by Baxter.

The third grouping I would put into place, as far as how these devices function mechanically, would be that of what NIOSH refers to as the air-cleaning technology devices, which would be OnGuard (also known as Tevadaptor), and also the B. Braun ChemoPen. These devices use a variety of filters to filter any vapor/sprays coming out of the system, any air going into the system as well. Of note, these systems do allow for air transfer between the product and environment.

3. Beyond the broad mechanical classifications of CSTDs, how can CSTDs be subclassified further?

There are really 2 basic types of mechanical interfaces a device can have within itself. It can either use a membrane-to-membrane with needles, where it actually has a needle that pierces through 2 membranes to enact a common fluid/vapor channel. Then as it comes out of the system, it physically wipes the needle off, reseals, and does not allow any drips to occur (dry connections).

Examples would be PhaSeal, Equashield I and II, Halo, the OnGuard Tevadaptor device, and the SureConnect product. The second one is a needleless process, which forms a common fluid/vapor channel, basically without the use of needles. What you have occurs either through leuring or sliding, where the device actually pushes open a port that is closed in the system and opens up a common fluid/vapor pathway between the vial device and the syringe device without the use of any needles.

When you disengage the system, it physically wipes off the tip of each 1 component as it disengages to minimize any leakage that would occur. Examples are ChemoClave, ChemoLock, Vialshield, SureConnect, and Texium.

4. What is the likely effect of USP <800> on the use and uptake of CSTDs, both in pharmacy and in nursing?

Firstly, I have nothing but accolades with regard to that chapter (http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings). I think the revision of USP <800> we saw come out in its final form is very easy to understand, and is probably 1 of the easiest chapters to understand within USP.

There is really not much to question, as far as things that we should be doing or must be doing from a recommendation standpoint. From a CSTD standpoint, it is very clear that it is a recommendation or a “should” for the compounding side of using a CSTD, and from the nursing or drug administration side, use of CSTDs is a “must” or a requirement.

Interestingly, the difference between compounding and administration, in my opinion, should have been a “must” for both. It does not make sense to dissociate the partnership between nursing and pharmacy, or the compounder and administrator. It is important to note as a disclaimer point, that the CSTD is only 1 step in a holistic hazardous drug safety program.

It is not the answer to everything, but it is a very important piece of it because it is a piece that actually keeps the system closed and protects the health care worker. We do know from a survey that was done in 2015 by Pharmacy Purchasing and Products magazine—they do an annual survey on compounding—that approximately 49% of the hospitals that responded stated that their pharmacy departments were using a CSTD, and that about 42% of nursing departments were using CSTDs, as well.

We have a disconnect where hospitals are not yet using these devices fully.Many are still using the old needle and syringe methodology, but the disconnect is that nursing and pharmacy departments should be synchronized on safety.

5. What are some key points for engaging nursing stakeholders and making sure that pharmacies get access to these systems as well as nursing departments?

It is unfortunate in today’s environment, with all of the information we have, that we have to convince people to use these devices to protect themselves. It is analogous to wearing a seatbelt as you drive a car, and we have to have laws that say, “If you don’t drive with a seatbelt on, you will get a ticket.”

We know what the best practice is. There is evidence that clearly shows wearing a seatbelt decreases deaths associated with car accidents. It is the same thing with the CSTDs. We know that it minimizes exposure to health care professionals of hazardous drugs if they use these devices.

One of the things that Tom Connor, PhD (lead author of the 2004 NIOSH Alert), and NIOSH group has done to help heath care providers with understanding hazardous drugs is assimilating 1 of the most robust listing of references about the risk and safe handling of hazardous drugs.

The articles are subcategorized into NIOSH publications; Recent Publications, Guidelines, Review Articles & Surveys; Effects of Occupational Exposure; Occupational Monitoring, and Environmental Sampling, Decontamination, Protective Equipment, CSTD systems and Work Practice (http://www.cdc.gov/niosh/topics/antineoplastic/pubs.html#sthash.C2VMKDi2.dpuf).

Anyone who has any question as to 1) concerns about exposure or 2) not believing that a concern actually exists, I would encourage them to go to the NIOSH website where you can view a summary of all of the articles, of which there are more than 80 citations on surveillance studies and case reports of health care professionals being exposed to these products, and what the repercussions of exposure to these products has been.

I think putting together a solid hazardous drug safety program starts with understanding what all of the risks are in the many reports published since 1979. Of note, all NIOSH-specific publications regarding hazardous drug handling are free of charge to access and download. Once we have established that the risk does exist, it is important to look at the tools we have to minimize the risk. This is not just a risk to pharmacy.

The risk applies to anyone who would handle these products. Nursing plays a big part in that. I think we always end up focusing on nursing and pharmacy, but we need to realize that using a CSTD also minimizes risk during the delivery process for individuals who are delivering these drugs to the floor, such as technicians or couriers.

More importantly, these CSTDs would also minimize any potential spills or off-gassing that would occur after the products are used and are placed in waste containers. It is not just nursing and pharmacy—it is very holistic in how these devices can work across the systems to minimize that risk potential.

6. How does USP <800> affect the layout of pharmacies and how does this affect costs?

In my opinion, this is a good time for pharmacists and pharmacy leaders to sit down with this document and upgrade their systems. It is ironic that these drugs, if you want to look at it from a revenue standpoint, generate a considerable amount of revenue for our institutions, and that revenue needs to be put forth towards upgrading and keeping the upgrades in these departments going.

As an example, radiology is not a department that continues to practice the same way it did 2 years ago, let alone 10 years ago. It is a department that continually keeps up with regulatory standards that surround managing and handling radiation and associated products, and they are continually updating their departments with safety initiatives that are put in place.

Pharmacy needs to have the same mindset. We need to educate our leadership within our systems to let them know that as new drugs come out and new evidence comes out, we too need to evolve with that understanding and not just say, “pharmacy has always done it, so we are not going to invest any money into this.”

This is the time to upgrade what the departments are doing to be able to do it in a safe manner that protects individuals. An example of this would be in, again, the radiology department they have the luxury of personal dosimeters, where they can measure individual radiation exposure in those providers working in that department. For nursing and pharmacy personnel who handling hazardous drugs, we do not have that luxury, we do not know if we have been exposed or not, and we do not know what the long-term effects of that exposure is continuously.

With that being said, we know that there are issues. Therefore, we need to progress with the safety recommendations and put them into place, and we have to be the educators. I think 1 of the things that I have seen historically, is that 1) people do not want to go through the efforts to see what the benefits are to their employees, and 2) they don’t want to go to their administration and ask for the equipment or practice changes because they are concerned about the perception of pharmacy as a cost center, or an expense center.

But pharmacy is not an expense center. If you do not want to spend anything for the safety of health care providers, then don’t handle these drugs and get out of that business. If you want to handle these particular products, then you need to conduct a gap analysis, define a compliance plan, and budget for the necessary changes needed to safely handle hazardous drugs to protect our health care providers and patients.

7. USP <800> classifies medications as hazardous drugs, including antineoplastic drugs, nonantineoplastic drugs that may affect cancer risks, and drugs that pay pose reproductive hazards. How can pharmacists develop a list of hazardous drugs for their specific institution?

First, I have to compliment NIOSH. In 2014, they created a 3-tiered classification of these products, which allows us to take a step back and ask: “Is it an all-hazards risk or a risk to a certain population of individuals who handle these drugs?”

For example, for all antineoplastic drugs that exist, the way in which they work is going to be an all-hazards risk to anybody handling those products. Therefore, we are going to want to have the highest standards in place for protecting individuals who are handling those products.

When we get into some of the other drugs, like group II or category II drugs, which are the non-antineoplastic hazardous drugs, including carbamazepine, phenytoin, and fosphenytoin, the package insert will tell you that these are hazardous products, but historically we have never treated these products that way.

One of the things that is really important to understand is that in the United States—and we are one of the few countries that does not do this—is we do not put hazardous markings on the packages of any of the drugs.

The manufacturer may take it upon themselves to say that a given product is an antineoplastic or to place a warning label on the packaging, but there is no consistent standard in the United States that tells anybody what they are handling is actually a hazardous product.

What we have is this recommendation list from NIOSH that says these are products that may be of concern if they are not handled appropriately. Another example of a non-antineoplastic drug that we have all collectively put into that realm is ganciclovir. We have always compounded this product as a hazardous drug.

First, we know it is a very basic drug and it has the potential to create DNA changes in normal individuals, so we want to protect individuals from that perspective. So why do we have a disconnect between ganciclovir and phenytoin? When you get into reproductive risks, drugs that are category III or level III drugs, these are products that, in my opinion, would pose the greatest risk to anybody who is trying to conceive children, who are already actively pregnant, or who may be breastfeeding.

This is where you would really want to stratify the risk to a specific population. In addition, in the NIOSH 2014 document, I would encourage pharmacists and nurses to look at all the appendices. It tells you exactly how to use that list. What some have done is taken the entire list and said, “This is what we have in our facility.”

Really, what this list is created for is to have people sit down and talk about medications and stratify the risk to individuals in their facilities. We went through the list of more than 200 drugs that are currently on all 3 lists, and we only had on our formulary about 121 those drugs. Comparing the list and your formulary is the first step. Then, you have to stratify the products into the 3 noted categories.

The NIOSH document has examples of how to handle these drugs within each of the risk stratification categories and is an excellent resource to make this an easy process. Of note, NIOSH has put out for comment the 2016 Hazardous Drug list for consideration.

8. Some hospitals use CSTDs to extend the use of vials of medication that do not contain antimicrobials, a practice known as drug vial optimization (DVO). In this way, less medication is wasted. How does this practice affect hospitals?

In light of the article by Bach and colleagues published in the British Medical Journal (Bach PB, Conti RM, Muller RJ, Schnorr GC, Saltz LB. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016.), researchers discussed the fact that manufacturers do not have enough vial sizes of dosage forms to use, and we are wasting billions of dollars each year because of that.

Within that study, there is no discussion about vial optimization programs, but this will be an important article to discuss DVO in greater detail. When we refer to DVO programs, first we must defer back to USP <797> on sterile compounding, regardless of what the literature says, because that is the set of standards we use in the United States for compounding sterile drugs.

We should not be deferring back to the manufacturers of the CSTDs for their articles to guide us on the compounding of a sterile drug. With that being said, what USP <797> does give you is a construct on how to conduct your own trials at your own site to do beyond-use dating.

Meaning you cannot take an article that has been published and then apply it to something you are doing at your facility unless you repeat that study and you have the same confirmation of results. The reason for that is multifactorial, but the main reason is that I may have superior or inferior engineering controls versus those individuals who actually did the study.

Secondly, I may have inferior or superior individuals who compound the products. Thirdly, it is important to consider the laboratory I am using for sterility and stability testing. I always defer people to USP <797> for guidance.

9. As a manager and clinician, what is your responsibility to your employees in ensuring their safety?

As a manager, I have the responsibility for 110 individual lives that work for Nebraska Methodist Hospital. It is my responsibility to read the standards, interpret them, and educate administration to make sure we get these safety standards put into place. We have used PhaSeal since 2001. We were 1 of the first community hospitals to actually bring it in—this is even prior to NIOSH.

When I actually heard the compelling evidence about how to protect individuals with these particular products, it’s 1 that we said we are going to do. We did not need a standard to tell us to do it. We saw that this was the safest thing for us to do for our employees. When NIOSH came out in 2004, it validated that we made the right decision.

That is what we as managers or as clinicians need to do all the time. We see drugs that come out that provide great strides and we are willing to bring them in for our patients. We need to do the same thing in protecting individuals when it comes to either compounding sterile drugs or handling hazardous drugs. We need to apply the same mentality of doing all that we can for our patients, to the standards that are out there for protecting health care providers.

10. What are some important points for pharmacists to know about CSTDs and what does the next 5 to 10 years hold in sterile compounding?

The first point is to read USP <800> now, not when the anticipated compliance date is in July 2018. This is the time to read it so that you understand what is going on, and then plan with your administrative personnel to budget for these changes you need to put in place, and that would also include implementing a CSTD.

The second piece is trying to understand what the CSTDs are and what they bring to the table. If you look at the normal syringe and needle process that we use today, which is commonly used for compounding drugs and for hazardous drugs, it is not the safe process. We have seen spills occur and we know that there is a risk for needle sticks.

The last thing you want is an inadvertent needle stick with these drugs. Also, you can contaminate the product on the outside, and that contamination goes up with the product to the nursing unit where they handle the product and they handle the patient. It is critical to understand what the CSTD brings to the table.

These are the only devices that were specifically designed to handle the attributes of hazardous drugs. Needle and syringe preparation has never been able to do that. Finally, it is key to foster a partnership between nursing and pharmacy. It is a collaborative approach that you need to see how we can make this an efficient and seamless process.

We did an efficiency study that actually has shown that using a CSTD actually decreases the amount of time from preparation to administration (Knolla K, Greisen D, Massoomi F. Time and motion study of 5 closed system transfer devices for IV chemotherapy drug compounding and administration).

People may think that using a CSTD causes more work, but we actually found it decreases the amount of work. In the future, I think that these drugs are going to get more and more complicated. I am concerned about research drugs as they come out, where we do not really know the hazards associated with them, and in a lot of the studies CSTDs are not used.

The sponsors of the studies want us to use a simple needle and syringe for fear of incompatibility associated with these products and their drugs. That needs to be investigated as well. I think in the next 5 to 10 years we are going to get out of the realm of compounding any sterile products because we realize that the number 1 risk to contamination of these products is human touch and the processes associated with that.

There are sites that do hundreds of doses a day, and to compound a very simple IV product requires greater than 20 steps for compliance. For us to assure that all of these steps are followed, it is difficult to say that every one of those steps are followed 100% every single time. We are going to see a shift to more stringent safety process to protect all parties involved.