USP-NF <797> Pharmaceutical Compounding - Sterile Preparations
One definition of sterile preparations is that they are anything that is not a nonsterile preparation. Although the statement may be true, it is not very helpful. A sterile preparation is one that does not have any microbial contamination. However, the only absolute method to prove that a preparation has no microbial contamination is to submit the entire preparation to a sterility test, thereby consuming it.
Sterility in a practical sense must provide a means to statistically ascertain that the preparation is not likely to carry enough of a microbial burden to cause patient harm. This is amplified in the first sentence of Chapter <797>: "The objective of this chapter is to describe conditions and practices to prevent harm, including death, to patients that could result from (1) microbial contamination (nonsterility), (2) excessive bacterial endotoxins, (3) variability in the intended strength of correct ingredients that exceeds either monograph limits for official articles or 10% for nonofficial articles, (4) unintended chemical and physical contaminants, and (5) ingredients of inappropriate quality in compounded sterile preparations (CSPs)."
The chapter grew out of the efforts of the National Association of Boards of Pharmacy (NABP), the USP, and the American Society of Health-Systems Pharmacists (ASHP) during a 20-year period to create a set of guidelines that would be universally accepted by manufacturers and compounders of sterile products and preparations. These guidelines were difficult to formulate and slow to be accepted. In a national survey conducted in 2003, only 5.2% of hospitals were in compliance with the guidelines. Chapter <797> became official on January 1, 2004, but its origins and its development are a fascinating story of regulatory process in the United States.
The first revision was available in 2008, but between January 2, 2004, and January 1, 2008, the USP identified components that needed revision based on external stakeholders' feedback and internal review. The chapter is organized to provide a foundation for the development and implementation of procedures for the safe preparation of low-risk, medium-risk, and high-risk level CSPs. The following are sections in the chapter:
- Responsibility of Compounding Personnel
- CSP Microbial Contamination Risk Levels
- Personnel Training and Evaluation in Aseptic Manipulation Skills
- Immediate-Use CSPs
- Single-Dose and Multiple-Dose Containers
- Hazardous Drugs as CSPs
- Radiopharmaceuticals as CSPs
- Allergen Extracts as CSPs
- Verification of Compounding Accuracy and Sterility
- Environmental Quality and Control
- Suggested Standard Operating Procedures (SOPs)
- Elements of Quality Control
- Verification of Automated Compounding Devices (ACDs) for Parenteral Nutrition Compounding
- Finished Preparation Release Checks and Tests
- Storage and Beyond-Use Dating
- Maintaining Sterility, Purity, and Stability of Dispensed and Distributed CSPs
- Patient or Caregiver Training
- Patient Monitoring and Adverse Events Reporting
- Quality Assurance (QA) Program
- Abbreviations and Acronyms.
The writing and institution of General Chapter <797> in the United States required enormous and sustained effort. But there are still many questions about how the chapter should be implemented and followed within an individual compounding facility. This is because all individual compounding facilities have unique or special situations that were impossible to foresee and detail in the chapter, which already occupies 45 pages in the USP on Compounding. The chapter was written in general terms so its provisions could provide guidance to many different facilities, but an implementation step that is applied in one facility may not be appropriate or possible in another facility.
Many commentaries have been published about the interpretation of the chapter, and the USP posts Frequently Asked Questions (FAQs) on the organization's website. Some of these interpretative references regarding personnel and types (categories) of preparations made are included. Additional interpretative references will be included in subsequent chapters for that appropriate material.