On June 3, 2019, the USP released the long anticipated final changes to Chapter 797. There are significant changes that each organization will need to comply with by December 2019. This month we begin with Part 1 of our 4-part series. This month, we will focus on the changes that relate to Scope, Categorization, Beyond Use Dating, Personnel training and competency, and Personal hygiene and garbing requirements.
USP Chapter 797 sets forth the minimal standards to be followed when preparing compounded sterile products (CSP). Sterile compounding is defined as “the combining, admixing, diluting, pooling, reconstituting, repackaging or otherwise altering a drug or bulk drug substance to create a sterile medication.” While the USP has no role in enforcement, Accreditation and Credentialing organizations may elect to enforce these standards. Chapter 797 goes further to define what must be sterile:
- Injections and Infusions
- Irrigations for INTERNAL body cavities (this EXCLUDES irrigations to the mouth, rectal and sinus cavities)
- Ophthalmic dosages (all forms)
- Products for pulmonary inhalation (this EXCLUDES products intended for local application to the nasal cavity).
- Baths and Soaks for live organs and tissues
- Allergenic Extracts
- Hazardous drugs (must also comply with USP Chapter 800)
IMMEDIATE USE COMPOUNDED STERILE PRODUCTS:
When CSP’s are compounded for direct and immediate administration to the patient, then the requirements associated with Category 1 and Category 2 compounding do not apply, provided the following conditions are met:
- Aseptic processes are in place and the organization has written policies that are designed to minimize the potential for contact with non-sterile surfaces, introduction of particulate matter and mix-ups with other conventionally manufactured products.
- The preparation is performed in accordance with evidence-based information for physical and chemical compatibilities,
- The preparation involves the combining of not more than 3 different products.
- Any remaining components not used to create the final product are discarded after preparation for the individual patient is completed.
- Administration begins WITHIN 4 HOURS following the START of the preparation.
- The product is labeled with the names and amounts of all active ingredients , the name or initials of the preparer, and the exact 4 hour time period within which administration must begin unless the product is prepared and administered by the same person of the person administering the product observed the preparation of the product.
CATEGORIZATION OF COMPOUNDED STERILE PRODUCTS:
Effective December 2019 compounded sterile products will be categorized into 2 groups: Category 1 and Category 2. Historically there were 3 categories, low, medium and high risk. The most important component of the category assignment is the associated Beyond Use Dating:
|Category||Beyond Use Date|
< 12 hours at Room Temperature
< 24 hours Refrigerated
>12 hours at Room Temperature
> 24 hours Refrigerated
The assigned category for a product is based upon the conditions under which the product was prepared. Additional sterilization steps may be required when the product is compounded using non-sterile products.
Proprietary Bag and Vial System Requirements:
When using a system such as addEASE, ADD-Vantage, or Mini Bag Plus the Beyond Use Date is determined by the intent:
- When the bag and vial are docked and activated and the product is IMMEDIATELY administered, the act of activating the bag and vial are not considered compounding and no specific environmental conditions apply.
- When the bag and vials are docked for future activation and administration, the docking process is considered compounding and the docking process must occur within an ISO Class 5 environment and the Beyond Use Dating assignment must not exceed the manufacturer’s labeling.
PERSONNEL TRAINING AND COMPETENCY
USP 797 requires the designation of a person who will oversee the training of personnel. The expectation is that all personnel involved in the compounding of Compounded Sterile Products must be initially trained and qualified (deemed competent) to perform these services. Your organization must have a written training program that describes:
- The required training
- The frequency of training
- The process for evaluating everyone’s performance
- How the training and competency assessment process will be documented
Competency in the following areas must be demonstrated and documented every 12 months:
- Hand Hygiene (Performance must be observed and documented every 6 months)
- Garbing (Proper donning and doffing of Personal Protective Equipment must be observed and documented every 6 months)
- Cleaning and disinfection
- Calculations, mixing and measuring
- Aseptic technique
- Achieving and/or maintaining sterility and apyrogenicity
- Use of equipment
- Documentation requirements of the compounding process which includes the master formulation and compounding records
- Principles of HEPA filtered unidirectional airflow within the ISO Class 5 environment
- Proper use of all primary engineering controls
- Principles of movement of materials and personnel within the compounding area
Keep in mind, that several of these competencies can be accomplished via written test.
PERSONAL HYGIENE AND GARBING
The proper application and use of Personal Protective Equipment is essential to both keep staff safe and achieve the level of protection needed during the compounding process. Hand Hygiene and Garbing must be observed and documented every 6 months. Gloved fingertip and thumb sampling is a required test that assesses the individuals skills in hand hygiene and garbing. Please note that this test consists of three separate performances of hand hygiene and garbing. Once the initial competency is completed, this testing must be performed every 6 months. In order to pass the initial assessment, the results of the biological testing must be zero colony-forming units all future tests are considered acceptable provided the Colony-forming units are less than 3. Additional details regarding the specific information that must appear on the competency assessment can be found in Section 2.2 of USP 797.
All persons entering the compounding area must be properly garbed and maintain proper personal hygiene in order to minimize the risk of contaminating the environment or CSP. Personal hygiene components that should be considered include, but are not limited to rashes, recent tattoos, oozing sores, conjunctivitis and/or active respiratory infections). Organizations need to work with their Human Resource and Occupational/Employee Health Departments to establish a process for managing staff that may present with any of the above.
It is also important to establish a clear communication process regarding what is permitted in the compounding area from a personnel management perspective. At a minimum:
No personal outer garments (No bandanas, jackets, sweaters, vests, hats).
No cosmetics can be worn in the compounding area.
All hand, wrist jewelry must be removed in order to minimize the risk of interfering with the functionality of the Personal Protective Equipment. This includes any piercings that may interfere with the mask and/or eye protection. Any exposed jewelry that cannot be removed must be covered.
Electronic devices including earbuds and/or headphones are not permitted unless an integral component of the compounding process.
Fingernails must be neatly trimmed and in their natural state. No nail polish, artificial nails or nail extenders can be worn.
Stay Tuned as next month we will explore the changes related to: Facilities and Engineering Controls, Microbiological Air and Surface Monitoring Requirements, Cleaning and Disinfection of the Compounding Area and Certification and Recertification requirements.
United States Pharmacopeia, USP 797- Pharmaceutical Compounding- Sterile Preparations , published June 3, 2019, Retrieved from https://www.usp.org/compounding/general-chapter-797