In This Section
General Questions about USP <797>
What is USP?
USP is a nongovernmental, scientific body responsible for setting standards for drug quality and related practices. USP also refers to the book of drug standards published by this organization.
What is USP <797>?
USP <797> is a general chapter in the USP that describes requirements for the preparation of sterile drugs, including radiopharmaceuticals.
What is a compounded sterile product (CSP)?
A CSP is a sterile drug product (including a radiopharmaceutical) that was prepared by compounding or underwent other handling or manipulation prior to administration.
Does USP <797> apply to radiopharmaceuticals?
In general, USP <797> applies to all CSPs including sterile radiopharmaceuticals.
Is the USP definition of compounding the same as the FDA definition of compounding?
No. Compounding under USP is much broader and includes many more situations than are subject to the FDA definition of compounding.
What is the immediate-use provision in USP <797>?
This is basically an exemption to USP <797> that allows certain sterile products to be prepared (compounded) without the need for special facilities (e.g., clean room or ISO Class 5 hood) and practices (e.g., full cleansing or gowning). Two key criteria for immediate-use exemption are avoidance of touch contamination and administration within 1 hour. Nevertheless, it is prudent to carry out immediate-use compounding in an area that is kept clean and orderly. Additionally, common aseptic techniques should be followed.
Who enforces compliance with USP <797>?
The USP<797> Convention is a nongovernmental, scientific body responsible for setting standards for drug quality and related practices but is not an enforcement agency. Enforcement of compliance with USP , therefore, falls upon other agencies.
Does USP <797> apply to physician offices?
Yes.
If USP <797> applies to physician offices, who will enforce the regulation in these locations?
USP <797> explicitly states that the standards do apply to all places where CSPs are prepared, including physicians' practice facilities. Enforcement most likely falls under state agencies, such as state boards of pharmacy, state boards of medicine, and state departments of health.
How will inspectors handle the fact that it will take some time to make all the changes, especially renovating facilities, needed for compliance with USP <797>?
Everyone understands that compliance will take some time to achieve. Inspectors will likely review your plans and progress toward compliance, rather than actual compliance, during this period of transition.
What will be the cost of compliance?
The cost of compliance is extremely variable, ranging from minimal cost for immediate-use exemption to thousands of dollars for simple low-risk compounding (e.g., laminar flow hood in a segregated area) and to more than $100,000 for medium-risk compounding (e.g., biological safety cabinet in a clean room).
Can you give some examples of situations in nuclear medicine and how requirements in USP apply?
- Unit-dose radiopharmaceuticals:
- If unit doses are administered, without further handling or manipulation, USP does not apply.
- Manipulation of unit-dose radiopharmaceuticals:
- If the unit dose is manipulated (e.g., normal saline is added to the syringe to dilute the contents), then USP standards do apply. Nearly all such manipulations can likely fall under the immediate-use exemption. Remember that the key components of the immediate-use provisions are the avoidance of touch contamination and administration within 1 hour. Dilution with normal saline, whether in a vial or in the syringe, is considered compounding under USP.
- Preparation of adjunct drugs (e.g., sincalide, furosemide, adenosine, and dipyridamole):
- Nearly all such preparation can likely fall under the immediate-use exemption. Remember that the key components of the immediate-use provisions are the avoidance of touch contamination and administration within 1 hour. Transfer of contents from a vial into a syringe is considered compounding under USP .
- Sterile radiopharmaceuticals or adjunct drugs used more than 1 hour after preparation (e.g., kits reconstituted with 99mTc):
- These products must comply with special facilities and procedures for low-risk level compounding.
- Low-risk level compounding must be performed in an ISO Class 5 containment device (i.e., laminar flow hood or isolator). For products to be administered in the range of 1–12 hours after preparation, the ISO Class 5 hood must be located in a segregated compounding area. For products to be administered more than 12 hours after preparation, the ISO Class 5 hood must be located in a clean room. Additionally, in both situations, specific procedures must be followed regarding hand hygiene, garb, personnel practices, etc.
- Elution of 99mTc generators:
- Elution must be performed in an ISO Class 8 or cleaner environment (e.g., clean room). Additionally, specific procedures must be followed regarding hand hygiene, garb, personnel practices, etc.
- Leukocyte labeling:
- Because labeling of leukocytes, with either 99mTc or 111In, includes more complex aseptic manipulations and is of longer duration, leukocyte labeling is generally considered to be medium risk level. Hence, these procedures must comply with facilities and procedures for medium-risk-level compounding.
- The compounding procedure must be performed in an ISO Class 5 biological safety cabinet that is located in an ISO Class 7 clean room. Additionally, specific procedures must be followed regarding hand hygiene, garb, personnel practices, etc.
My local commercial nuclear pharmacy told me that "797 is all about interpretation and how you can best fit it into your practice." The pharmacy also mentioned that "nuclear medicine should be allowed some forgiveness in certain cases because of the nature of what we do." These explanations are "safe" blanket statements that I wouldn't repeat to an inspector. Could you please direct me to a definitive source on how I can abide by 797 in my situation?
It is true that USP involves some interpretation. Hence, it is not surprising that there may be differences of opinion regarding specific compliance requirements. Individual practitioners should consult with their facility's pharmacy department, administration, state board of pharmacy, and legal counsel. USP and the USP Guidebook to Pharmaceutical Compounding—Sterile Preparations are the definitive source documents and also provide some general guidance for compliance.
It was my understanding that all USP general chapters numbered 1000 and below were considered to be federal law. Yet after reading several articles, these general chapters are portrayed as optional or as if applicability varies from state to state. We have spent considerable time and resources becoming compliant but find very inconsistent company among our colleagues. What's the real scoop?
Generally, USP general chapters numbered less than 1000 are "enforceable" whereas general chapters numbered greater than 1000 are "informational." USP general chapters numbered less than 1000 are not federal law per se, but rather may be cited by FDA rules and guidance, and thereby enforced by FDA. Enforcement of USP as a specific chapter is variable depending on particular facility status, state regulations, etc.
Could you please give me any information you have concerning the date when hot labs need to be in compliance with USP 797.
There is no exact answer to this question. Deadlines for achieving compliance depend on the particular enforcing entity. Some State Boards of Pharmacy have already announced dates for expected compliance. The Joint Commission has not formally adopted USP at this time, but inspectors are looking for compliance with existing local requirements (e.g., applicable State Board of Pharmacy rules). Compliance with is regarded as a significant safety-related medication issue, however, so Joint Commission standards may change in the future. June 1, 2008 is the effective date for . Since is an FDA-enforceable general chapter, FDA can and will exercise its “enforcement discretion” if they notice any problem of pharmacy compounding practice that affects public health.
Is there any mechanism whereby a facility can become "certified" as USP compliant?
There is no USP compliance certification per se. That is, there is no organization or other entity that specifically inspects for USP compliance and awards a certificate of compliance (or “seal of approval”). If a facility is subject to USP compliance (by state board of pharmacy rules for example), is inspected and passes the inspection, then the facility may legitimately claim to be USP compliant. Otherwise, claims of USP compliance are based on professional judgment.