Your Guide to Understanding USP General Chapter <825> Radiopharmaceuticals – Preparation, Compounding, Dispensing and Repackaging

Published: April 8, 2024

Radiopharmaceuticals represent a unique class of drug products where compounding and other handling activities include the use of radionuclide generators, the preparation of commercially manufactured radiopharmaceutical kits, the dilution of FDA-approved multi-dose vials, the labeling of human blood products with radionuclides, the preparation of patient-specific radiopharmaceutical doses and more. These activities occur in an environment where individualized patient needs and the safe handling of radioactive materials demand a high level of care and clearly defined standards. These standards are developed by the United States Pharmacopeia (USP). One example is USP <797>, which outlines the necessary procedures for preparing compounded sterile medications in a way that reduces risks such as contamination, infection or incorrect dosing.

However, given the unique characteristics of radiopharmaceuticals, complying with USP <797> standards was next to impossible for nuclear medicine professionals. Thus, a new reference chapter was created, USP <825> Radiopharmaceuticals—Preparation, Compounding, Dispensing, and Repackaging. The new chapter adds an expanded scope and is specific to the nuances of radiopharmaceuticals, while also adding the concepts and disciplines of radiation safety.

What is USP <825>? 

USP <825> provides uniform minimum standards for the preparation, compounding, dispensing, and repackaging of sterile and non-sterile radiopharmaceuticals for humans and animals that occur as part of state-licensed activities (e.g., the practices of pharmacy and medicine). USP <825> describes facilities and engineering controls, personnel training and qualifications, and procedural standards for processing radiopharmaceuticals in nuclear pharmacies, nuclear medicine areas in hospitals and clinics, and other healthcare settings that utilize radiopharmaceuticals. It applies to all individuals who prepare, compound, dispense or repackage radiopharmaceuticals. Applicable individuals consist of authorized nuclear pharmacists (ANPs), and authorized user (AU) physicians, as well as individuals working under their supervision. This includes, but not limited to, student pharmacists, nuclear pharmacy technicians, nuclear medicine technologists and students and physician residents and trainees.

What Are the Differences Between <797> and <825>?

There are several key differences between USP chapters <797> and <825>, with the USP <825> focusing on:

  • Scope of Practice: USP <825> applies to all individuals who prepare, compound, dispense, or repackage radiopharmaceuticals, both sterile and non-sterile. The practice settings include nuclear medicine departments in hospitals and clinics, nuclear pharmacies, nuclear cardiology clinics, and other specialty clinics.
  • Radiation Safety: Among the main differences between the two chapters are the requirements for radiation safety. Although exposure to ionizing radiation cannot be avoided entirely, it can be minimized through a robust radiation safety program. As Low as Reasonably Achievable (ALARA) is the goal for nuclear medicine workers. There are four key elements in achieving ALARA:
    • Time: Radiation exposure is directly proportional to the quantity of radioactive material (RAM) handled and the time spent handling it; therefore, minimizing the handling time will minimize the radiation exposure.
    • Distance: Radiation exposure follows the inverse square law; increasing the distance from radioactive materials will decrease the exposure by the square of the distance. Thus, operators may utilize techniques to increase distance (eg, tongs or other remote handling tools).
    • Shielding: Personnel exposure to radiation decreases with the use of shielding materials, such as lead and tungsten syringe shields and vials shields.
    • Radiation Contamination Control: Radioactive materials contamination, such as spills, drips, sprays, and volatility, is a safety concern, and materials such as disposable absorbent pads that are low-lint are used to contain and quickly remove contamination. In addition, vertical laminar airflow hoods are utilized to ensure that radiative contamination does not blow at the operator.
  • Facilities and Environmental Controls: Whereas USP <797> defines a segregated compounding area (SCA) as an area of unclassified air quality with a PEC, USP <825> instead has a segregated radiopharmaceutical processing area (SRPA) with a PEC in ISO class 8 air quality, which is necessary to protect the eluting of the Tc-99m/Mo-99 generators needed to prepare many radiopharmaceuticals.
  • Microbiological Air and Surface Monitoring: Whereas USP <797> has microbiological sampling occurring under dynamic or simulated conditions, USP <825> instead suggests that this process occurs after the radiopharmaceutical processing but prior to cleaning and disinfecting. This change aims to better protect the monitoring technicians from being exposed to radioactive materials.
  • Cleaning and Disinfecting: After microbiological air and surface sampling has been conducted, radiation safety must be observed before the cleaning and disinfecting of the buffer area and anteroom can occur. This process must include the following steps:
    • First, the absorbent paper in the PEC must be removed and checked for radioactive contamination with a Geiger counter, and any contaminated paper must be placed in an appropriate lead barrel.
    • All surfaces inside and surrounding the PEC must be checked for contamination with a Geiger counter, and wipes must be taken and sampled for activity.
    • If contamination is found, it must be thoroughly decontaminated. If the levels of radiation are unacceptable, lead covered in plastic must cover the area for 10 half-lives of the isotope.
  • Master Formulation Records: When doses are changed or altered, a master formulation record (MFR) is required. For example, when a diagnosis is needed in cases of diabetic gastroparesis, Tc-99m sulfur colloid is commonly added to scrambled eggs for consumption. The data needed for the MFR includes but is not limited to:
    • Name of the radiopharmaceutical
    • Name, identity, strength, purity, and quality of ingredients
    • Range of radioactivity
    • Range of volume
    • Quality control tests to be performed for final release
    • Reference source for BUD assignment and storage conditions
    • Equipment to be used and detailed procedures

How RLS Radiopharmacies Can Help

With the advent of USP <825>, many institutions may find themselves navigating uncharted territory. That’s where specialized services like those provided by RLS Radiopharmacies come into play. At RLS, all 31 of our locations are equipped with expertise in the realm of radiopharmaceutical preparation, compounding, dispensing and repackaging, and our experts are here to offer support in matters related to compliance with USP <825> standards. We can assist you in implementing proper procedures and protocols that are central to the safe handling, compounding, and dispensing of radiopharmaceuticals in alignment with USP <825>. 

For institutions and practitioners, adherence to USP <825> is not just about regulation compliance but a commitment to excellence in patient care and safety. In navigating these requirements, RLS Radiopharmacies strives to be an indispensable partner, providing the expertise and guidance to maintain the highest standards in nuclear medicine. For help with USP <825> compliance matters, we encourage you to reach out to your local RLS representative. Our professionals are here to help.

More About RLS Radiopharmacies

RLS is America’s only Joint Commission-accredited radiopharmacy network, with 31 radiopharmacies covering more than 85% of the population. Every RLS radiopharmacy houses cutting-edge clean rooms and is fully equipped and aligned to USP <797>, USP <825> and ISO 14644-1 compliance standards. Every RLS radiopharmacy is led by experienced nuclear pharmacists, who, along with nuclear technicians, in-house couriers and a robust delivery fleet, ensure every SPECT, PET and therapeutic product the company offers is meticulously prepared, dispensed and distributed to the company’s more than 1,500 customers without fail. For more information, please visit rls.bio.

 

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