Top 10 Takeaways Every IV Vitamin Therapy Practice Should Know About the Recent Revisions in USP 797

On Nov 1, 2022, the United States Pharmacopeia (USP) released the final publication of USP 797. The USP 797 standards apply to all persons and places that prepare compounded sterile preparations (CSPs) for human and animal patients. If you are a pharmacist, technician, nurse, physician, veterinarian naturopath, dentist, chiropractor, hospital, health care institution, infusion facility, or the like, you are subject to these guidelines. You are also subject to potential inspection by State Boards of Pharmacy where you hold licensure and Federal requirements and possible inspections as dictated by the FDA.

Here are the top 10 takeaways that apply to businesses administering intravenous (IV) vitamin therapy. Businesses will have up to 1 year to adjust to the final publication, amend standard operating procedures, and train staff on new guidelines and policies that is has set forth.

#1. Are you compounding when you prepare IV vitamins and subject to USP 797?

If you add more than one compounded preparation to a sterile bag for administration to a patient, then the answer is yes, you are subject to USP 797

#2. Which category are you?

Under the new categories defined in Section 1.5, most IV vitamin therapy providers can confidently refer to their business practices as a Category 1 or 2. The facility design around the cleanroom determines the Category that applies to your facility which determines the beyond-use date (BUD) within which they must be used. Category 1 is an ISO Class 5 air quality surrounded by the least controlled environmental conditions; Category 2 is within an ISO Class 5 Cleanroom surrounded by an ante and buffer room.

#3. How does the Category affect your BUD?

Besides compounding environment, the primary difference between Category 1 and Category 2 CSPs is the maximum allowable BUD that can be assigned to these preparations.

Category 1—The maximum permitted BUD is 12 hours when the preparation is stored at a controlled room temperature (20-25°C), or 24 hours Refrigerator (2-8°C).

Category 2—The maximum permitted BUD from sterile starting components 45 days Controlled Room Temperature (20°-25°C), 60 days Refrigerator (2°-8°C), 90 days Freezer (-25° to -10°C)

#4. Does this mean you are required to have an ISO Class 5 cleanroom?

The ISO Class 5 air quality is considered the working standard for sterile and non-sterile compounding when preparing single-dose vial preparation, IV bags, and syringes. ISO Class 5 air quality is required in the direct compounding area and must contain less than 3,520 particles per cubic meter by definition of ISO 5.

It would serve as best practice for every IV vitamin therapy facility to have an ISO 5 Cleanroom or ISO Class 5 Vertical Laminar Flow Workstation. Keep in mind they are both required to be recertified every 12 months. Also, all monitoring equipment must be calibrated or verified for accuracy as recommended by the manufacturer or every 12 months. This also includes your humidity sensors, pressure monitors, and thermostats.

#5. Does your IV vitamin practice classify as Immediate-Use?

According to Section 1.3 for Immediate-Use Compounding of CSPs for direct and immediate administration are not subject to the requirements for Category 1, Category 2, or Category 3 CSPs, if they meet the following criteria:

• They do not exceed more than 3 sterile products
• Use aseptic techniques, processes and procedures
• Have written SOPs in place, minimizing potential contact with nonsterile surfaces, including but not limited to the possible introduction of particulate matter or biological fluids and mix-ups with other conventionally manufactured products or CSPs
• Your personnel must be trained and be able to prove competency in all tasks according to the business SOP

#6. Why does the Immediate-Use CSP provision allow for administration to begin within 4 hours following the start of the preparation?

The Immediate-Use CSP provision was revised to allow practitioners up to 4 hours to begin administration and to balance the need for ensuring CSP quality with timely access to medication in a variety of health care settings. This provision will apply to almost all mobile IV practitioners and businesses serving walk-in patients.

These are expected to only be prepared as a single-dose container that is discarded after the preparation is complete. The administration must be within 4 hours after compounding and then immediately discarded. Compounders can prepare multiple doses of immediate-use CSPs intended for use in one or more patients in a single batch if they are also within the Section 1.3 criteria.

#7. What does “directly administered” mean in Section 1.3 Immediate-Use CSPs?

“Directly administered” refers to the dose being prepared and then immediately administered by the person who prepared it, or the administration is witnessed by the person who prepared it. There is risk involved if a CSP is unlabeled and the person who compounded it is not the person administering or present for the administration. If this is the case, then the preparation must be labeled with the names and amounts of all active ingredients, the name or initials of the person who prepared the preparation, and the 4-hour period within which administration must begin.

#8. What are the training and competency assessment requirements for personnel who only prepare Immediate-Use CSPs?

Training and competency assessment requirements are determined by the specific tasks performed and the facility’s SOPs. These must include aseptic processes with an emphasis on minimizing the potential for contact with non-sterile surface surfaces, introduction of particulate matter or biological fluids, and potential mix-ups with other conventionally manufactured products or CSPs.

#9. Is it considered compounding if you draw a dose from a conventionally manufactured container or spike an IV bag for Immediate-Use?

No, withdrawing a dose from a container or spiking an IV bag of a conventionally manufactured sterile product without any further manipulation is considered administration rather than compounding and is out of the scope of USP Chapter 797. Unless the bag has another product added, then it would be considered compounding and subject to the requirements of 797.

#10. Are you required to print and produce your own SOPs as well as training and testing?

Yes. Section 2 reviews the Training and Evaluation for all compounding personnel. Positions identified as the preparer or the administrator must prove that they can reliably demonstrate competency through written testing and proficiency through hands-on demonstration of skills every 12 months. The business must develop an SOP and institute this training and testing for any personnel directly handling or entering the compounding area in the following areas:

• Hand hygiene
• Garbing
• Cleaning and disinfection
• Calculations, measuring, and mixing
• Aseptic technique
• Achieving and/or maintaining sterility (and apyrogenicity if compounding with nonsterile components)
• Use of equipment
• Documentation of the compounding process (eg, master formulation and compounding records)
• Principles of high-efficiency particulate air (HEPA)-filtered unidirectional airflow within the ISO Class 5 area
• Proper use of PECs
• Principles of movement of materials and personnel within the compounding area

It is important that the business owners and practitioners who have entered the IV vitamin therapy industry fully embrace the heightened safety and industry standards that they are subject to. Although they are not pharmacies themselves, they are compounding when they combine sterile products and it will have grave consequences if they are not exceeding these standards as they serve patients. As a result of mistakes in compounding errors, including but not limited to patient harm and death, there is an emphasis to continuously improve the state of compounding to meet the demand of the many diverse industries that perform the compounding of IV medications. The revised version of USP 797 provides heightened personnel and environmental monitoring and controls, which will aid in meeting this demand. These changes will require personnel and financial investments for new or increased frequency of certain monitoring and testing as well as operating within the required BUD that your facility and storage will permit. All practitioners are advised to review their particular State Board of Pharmacy and Professional License limitations that specify stricter state laws or statutes regulating or pertaining to Compounding Pharmacy and the use of compounded products.