IV Hydration Therapy and Compounding Guidelines
What is USP 797?
USP is the United States Pharmacopeia, a nonprofit organization that creates guidelines for compounding drugs to ensure quality, safety, and sterility. Many states have adopted the USP guidelines as governing law, including Minnesota. USP 797 is the set of guidelines that apply to compounded sterile drug preparations or CSPs. It should be noted that USP’s position is that the 797 guidelines “serve as the minimum standards for the preparation of CSPs for human and animal drugs” and that USP plays no role in enforcing the guidelines. Changes to USP 797 will go into effect on November 1, 2023, therefore it is important to be aware of the changes and how they affect IV hydration clinics. Holt Law is available to assist in amending your current policies and procedures to be in compliance and to create standard operating procedures if your clinic decides to compound on site.
What is sterile compounding?
Sterile compounding includes all the following:
-combining;
-admixing;
-diluting;
-pooling;
-docking a proprietary bag and vial system for future activation and administration;
-reconstituting;
-repackaging of a sterile product or preparation from its original container into another container;
-altering a drug or bulk drug substance in any way to create a sterile preparation; or
-preparing a single dose of a conventionally manufactured product differently than the EXACT directions contained in the manufacturer’s approved labeling.
What is not considered sterile compounding?
Certain practices do not fall under the category of sterile compounding and therefore are not subject to the USP 797 guidelines. Applicable ones include:
- Docking and Activation of proprietary bag and vial system in accordance with the manufacturer’s labeling for immediate administration for an individual patient;
- Administration;
- Withdrawing a dose from a container or a conventionally manufactured sterile product without any further manipulation before administering;
- Spiking an IV bag; and
- Conventionally manufactured sterile products that are prepared for administration for a single dose for an individual patient in accordance with the manufacturer’s approved labeling.
What does it mean to “prepare per manufacturer’s approved labeling?”
The labeling or materials provided by the product’s manufacturer must be followed exactly, including information for the diluent, the resultant strength, the container closure system, and storage time. If the label is missing any of that information or the medication is put into a different container, then it is considered compounding and therefore must abide by USP 797 guidelines.
What is “Immediate Use”?
“Immediate Use” has been interpreted differently by different organizations over the years. Many IV hydration clinics have been compounding sterile drug preparations (CSPs) on site but have been abiding by the immediate use provision of USP 797, which does not require drugs to be compounded in ISO Class 5 conditions.
The old USP definition for immediate use included the words “emergent-use situations” or “urgent” and was to only apply when abiding by low-risk compounding procedures would cause risk or potential harm for a patient because of the delay. The new USP 797 guidelines have removed the “emergency use” portion out of the immediate use category, have extended the beyond use date (BUD), and have increased preparation requirements if medications are going to be compounded for immediate use.
How does a practitioner abide by the Immediate Use requirements?
If a medication is prepared for immediate use, all of the following requirements must be followed:
- Aseptic techniques, processes, and procedures are followed, and written standard operating procedures (SOPs) are in place to minimize the risk of contact with nonsterile surfaces, particulate matter or biological fluids being introduced, and mix-ups with other conventionally manufactured products or CSPs.
- All personnel who prepare CSPs are trained and have demonstrated competency in aseptic processes as they relate to assigned tasks and the facilities SOPs.
- The preparation is performed according to evidence-based information for the drug’s physical and chemical compatibility. This would include the product’s approved labeling instructions, the stability of the products, and compatibility studies.
- The preparation involves no more than 3 different sterile products.
- Any unused starting components from a single-dose container must be discarded after preparation is complete. Single-dose containers must not be used for more than one patient.
- Administration must begin within 4 hours following the start of the preparation of the CSP. If administration has not begun within 4 hours, the CSP must be safely discarded. This means that no compounded mixtures can be batched or stored. Ideally, there are no steps that occur between compounding and administration.
- No hazardous drugs are used in the compounding.
- Unless the person who prepared the CSP directly administers it or witnesses the administration to the patient, the CSP must be labeled with the names and amounts of all of the active ingredients, the name or initials of the preparer, and the 4-hour time period for which administration must begin. As a practice, it is wise to label regardless of whether the preparer directly administers the CSP.
What else should be taken into consideration besides following only the immediate use guidelines?
Since USP 797 is a minimum standard, there are other risk determinations that should be evaluated before deciding if a CSP should be compounded outside of ISO 5 Class 5 conditions. These risk determinations include:
- Where the preparation is being made;
- The number of components or the number of aseptic breaches needed to compound the preparation; and
- The complexity of the compounding process.
Additionally, the compounding personnel must take into consideration the potential danger of exposing their patients to microbial bioburden and the microbial growth factors influenced by product storage time, temperature, and product ability to support microbial growth, surface and time exposure of critical sites, and microbial bioburden in the environment. If compounding will take place anywhere other than a segregated area that is sterilized multiple times throughout the day, the environment can further influence the risk of microbial growth.
And finally, there is the opinion of the Minnesota Board of Pharmacy that does not believe that the immediate use provision was meant to be utilized out of convenience. Previous USP 797 guideline commentary also stated that when circumstances make the risk level determination unclear, guidelines for the more stringent category should prevail. However, Minnesota law follows the USP 797 guidelines, so the law will be according to the revised immediate use guidelines that will go into effect on November 1, 2023.
Ultimately, a practitioner needs base their decision to compound on several factors and determine the safest and cleanliest option for their patients and practice. Choosing to err on the side of chance or convenience could have major implications if a patient were to contract an infection that could have been prevented with compounding in a more sterile environment.
Who oversees IV Hydration Clinics?
While there is not a specific state license to open and operate an IV hydration clinic, that does not mean that they are not regulated. The FDA and the US Federal Trade Commission are becoming increasingly concerned and aware of the need for stricter regulation on IV hydration clinics and are working to engage federal and state regulators to involve the appropriate licensing boards to inspect clinics and ensure compliance.
See: FDA highlights concerns with compounding of drug products by medical offices and clinics under insanitary conditions. fda.com
How can an IV Hydration Therapy Clinic comply?
There are a several different options for hydration clinics to be in compliance, one which requires major changes, one that requires moderate changes, and four that require less drastic changes in operation. Which route the clinic decides will be dependent on what works for the clinic, how much a clinic is willing to spend to make changes, and the amount of risk the clinic is willing to assume.
The Safest (and most expensive option): Build an ISO 5 Clean Room.
Building an ISO 5 clean room can be quite costly, ranging anywhere from $180/sq.ft. to $2800/sq.ft. and for modular clean rooms, they can cost up to $500,000. ISO 5 clean rooms are the recommended environment for compounding IV bags and the classification is according to the maximum number of particles in the air, per cubic meter. An ISO 5 clean room must have less than 100,000 particles per cubic meter. The air must be exchanged 240-480 times per hour to ensure the particulate ratio, so a HEPA filter must be installed in the ceiling of a clean room along with ceiling fans. Other requirements of a clean room include ceiling tiles that are clean room grade and seamless vinyl flooring. Depending on the material of the walls, they may need to be painted with epoxy paint. Additionally, before a person enters a clean room, they must remove any clothing that does not meet cleanroom requirements, cosmetics and makeup must be removed, as well as any jewelry. To enter, a person must also wear appropriate garb that includes shoe covers, a face mask, a gown, and a hair cover. All products that are brought into the clean room must be wiped down with at least 70% isopropyl alcohol or a bleach solution and the clean room and ante-room must be disinfected daily. It is recommended to always consult or hire a professional who has experience in designing and building a clean room before undertaking renovations with a traditional contractor.
The Moderate Price Option: Purchase a USP 797 Compliant Hood.
ISO Class 5 Laminar flow hoods range anywhere from a couple thousand dollars up to as much as $25,000. Most IV hydration clinics will not require a hood that costs more than a few thousand dollars because they don’t need the ability to hang eight to twelve bags at one time. If purchasing a hood, it is important that the IV hydration clinic has a room that can accommodate the hood so it is separate from the common areas or patient care areas. When using a hood, it is recommended that all garbing requirements are abided by as if it were an ISO 5 clean room including shoe covers, face masks, gowns, and hair covers.
Other Good Options that are More Cost Effective:
- Strictly adhere to the “Immediate Use” section of the USP 797 guidelines.
Strictly adhering to the immediate use classification is still considered to be in compliance, if all of the requirements are followed. (See the list above for all requirements of the immediate use classification.)
- Use a proprietary bag and docking system.
A proprietary bag and docking system is a product that can be purchased which includes a specialized IV bag and a vial with medication in it. The vial is uncapped and screwed into a port in the IV bag and then by manipulating the vial, an internal plug releases and the medication empties into the IV bag. The administrator thoroughly shakes the bag to mix the solution, it is spiked, and then administered to the patient within the recommended period of time. One criticism of the proprietary and docking system is that at times, the medication does not fully empty into the bag and it can result in a decreased medication dosage and a varied ratio of medication to dilutant.
- Push meds in an IV for simpler infusions.
Spiking an IV bag is not considered compounding. Withdrawing and administering a dose from a single use container that is pre-mixed and does not require dilution or mixing with any other products is not considered compounding. And neither is administering a pre-mixed, pre-filled syringe. So, one option is to spike the IV bag and begin administration and then push the vitamin/supplement mixture into the IV line. This is only an option, however, if the vials that are purchased are 100% ready-to-administer or if pre-filled syringes are purchased and used in the push administration. One downside to this method is that is requires the person power of a practitioner to administer and push the syringe and depending on the medication, it may require a slow push over a span of several minutes. Another downside is that the options of vitamin and supplement mixtures that can be purchased this way may be more limited than the traditional mixing and compounding options.
And remember, all syringes, even if they are pre-mixed and pre-filled, need to be labeled for safety with what the syringe contains and the patient’s identifying information.
- Order your IV bags premixed from a 503B Compounding Pharmacy.
503B compounding pharmacies register with both the FDA, the DEA, and the state board of pharmacy in which they are located. While compounded drugs are not regulated by the FDA, the facility itself is. 503B compounding pharmacies can be a great option for IV hydration clinics because the clinic can be confident that the IV bags are compounded in a sterile environment and the clinic assumes less risk than mixing and introducing microbial growth factors onsite. Make sure to do significant research before ordering from a 503B compounding pharmacy as they are not all equally reputable and exact dosage in mixtures can vary. One drawback of ordering from a 503B compounding pharmacy is that it will be more expensive than compounding onsite. Another drawback is many 503B compounding pharmacies require mixtures to be ordered in bulk, so clinics may find it necessary to reduce the options of vitamin and supplement mixtures available to patients or risk investing significant amounts of money in product that must be properly stored and used before its expiration. Ordering all of the possible mixtures and then storing them could end up being more than most clinics want to take on.
What needs to be included in the Standard Operating Procedures (SOPs) for compliance with the Immediate Use Guidelines?
Clinic policies will need to change to specifically explain not only the clinic’s process of compounding for immediate use, but also to indicate who is allowed under the clinic policies to compound and administer medications.
The Designated Person: Clinics will need to designate one or more individuals to be the “designated person” that is responsible for the facility’s performance, operation, and personnel in the preparation of CSPs and other functions that fall under USP 797 guidelines. This person will also need to be named in the clinic’s SOPs and may need to register with the state. The duties of the designated person will include, but are not limited to:
- Ensuring all compounding staff are fully trained and show competency in USP 797 guidelines while compounding;
- Overseeing and monitoring compounding activities and if a person or process is out of compliance, taking immediate action; and
- Ensuring the SOPs are fulling implemented and strictly followed.
Drafting the SOPs: Clinics will need to create and implement standard operating procedures that include exactly how compounding personnel will sterilize the environment, wash their hands, don protective garb, prepare the elements of the CSP, label the CSP, etc, and must be according to the 797 immediate use guidelines.
Another Consideration:
Clinics may not use prefilled saline syringes to reconstitute a mixture or dilute a substance and then draw the mixed solution back into the same syringe or a different syringe. This also includes only using part of the syringe for dilution and drawing up the mixture back into the syringe or drawing up any other mixtures to add to the prefilled saline. The reason is that pre-mixed saline flushes or syringes are considered a medical device and are not approved for dilution or administration of IV push medications.
What about other Minnesota rules/laws in this area?
Most of the other Minnesota rules/laws are related to acceptance of medications and storage.
The important ones to know are:
- Minn. Administrative Rules 6800.9951, stating that practitioners who dispense drugs should have a separate locked storage area to store drugs and the only people who have access to it are those who have the legal authority to dispense or those under their direct supervision.
- Minn. Administrative Rules 6800.9952, Subd. 2, stating that a practitioner who dispenses should reduce all drug orders to a written prescription and that patient chart records do not qualify as a prescription record.
- Minn. Administrative Rules 6800.9954, stating that a practitioner engaged in dispensing drugs shall keep on file a record of drugs received, administered, dispensed, sold, or distributed. The records shall be readily retrievable and maintained for at least two years.
Ultimately, the best course of action is to consider what is going to be most safe and sterile for patients. If a clinic is unsure about how to be in compliance, they can always hire a pharmacy consultant who has knowledge and experience in the area of compounding and how to remain in compliance with the USP 797 guidelines.
Sources and other informational sites: