The United States Pharmacopeia (USP) Convention was first held in 1820 when 11 physicians gathered to set standards to ensure that a prescribed medicine would be the same, regardless of where it was created or where a patient lived. USP reference standards for pharmaceutical development and manufacturing confirm accuracy and reproducibility through rigorous testing and evaluation by multiple independent laboratories, including the USP, as well as commercial, regulatory, and academic laboratories. USP publishes publicly available, official documentary standards for pharmaceutical ingredients in the USP-National Formulary, which links directly with its pharmacy reference standards. The process for creating reference standards is complex, and involves extensive testing, analysis, and laboratory results—in short, science and evidence.
The USP has been revered for its scientific, evidence-based standards, general chapters, and monographs on ingredients, products, and preparations of medicines. “Through our rigorous science and the public quality standards we set, USP helps protect patient safety and improve the health of people around the world.”1 However, when it began to create standards for the professional practice behavior and operations of healthcare professionals, it veered sharply away from the use of science as the basis for its standards. These professional practice standards are written by volunteer committees recruited every 5 years. USP offers these committee members the chance to use their opinions as the basis for policy. “USP volunteers are called upon to utilize their best personal, professional, and scientific judgment to benefit global public health.”2
Many of the overly prescriptive details of both USP General Chapter 797 Pharmaceutical Compounding – Sterile Compounding (USP <797>) and USP General Chapter 800 Hazardous Drugs – Handling in Healthcare Settings (USP <800>) are simply the opinions of a very limited number of individuals, with little operational experience in nonpharmacy healthcare settings such as medical practices and other facilities.
Recommendations should not be made or suggested as mandates if there is a lack of defensible scientific, clinical, epidemiologic, and/or statistical evidence to support them. The harm that can be done to the healthcare system by encouraging compliance with non–science-based standards for professionals goes far beyond the mission or purview of the USP.
The USP notes that it was granted the authority to create general chapters by the USP Convention, which is not an external regulatory or governing authority. The USP does not enforce its chapters but aggressively promotes them as enforceable, thus creating a ready market for the purchase of its general chapters. Once official, these standards must be purchased solely from the USP for individual use, and the cost is substantial. Purchasers include any interested or affected organization that may have the standards applied to them, as well as anyone providing guidance or choosing to use the standards as enforcement. The bottom line is that these “professional standards” have become an important source of income for the USP.
In recent years, the USP convened “Expert Committees” to author USP general chapters for professional practice standards, beyond the ingredient-based standards for which it was known. USP General Chapters 795 Pharmaceutical Compounding – Non-Sterile (USP <795>), USP <797> (2008 version), and USP <800> each delve specifically into the policies, procedures, training, facilities, documentation, and general operations of the entities to which the standards may be applied—a far cry from oversight of the ingredients of medicines.
Expanding the focus of USP chapters to reach into the deepest aspects of healthcare operations brings with it a significant cost to society, facilities, and patients. Layering detailed onerous requirements for compliance with published standards can lead to negative consequences that may far outweigh the risks the standards were written to avoid. USP <800> is the most far-reaching of the 3 professional standards chapters, and the most controversial. In the introduction, it states that it shall apply to the receipt, storage, compounding, dispensing, administration, and disposal of sterile and nonsterile products and preparations for all healthcare personnel who handle hazardous drug preparations and all entities that store, prepare, transport, or administer hazardous drugs (eg, pharmacies, hospitals, and other healthcare institutions; patient treatment clinics, physicians’ practice facilities, or veterinarians’ offices). The Compounding “Expert Committee” is comprised of 15 members, with little diversity in their membership to include perspectives from the field of the affected entities.
The chapter appears to have been written from the perspective of an ideal, sterile world, with a lack of awareness of the real-world impact and application of the standards on the variation of care delivery in such diverse entities.
The chapter covers a wide range of standards, including the following:
Although there are 45 references listed at the end of USP <800>, there are no subscripts tying any of those references to details inside the document. The absence of tagged number references added at the end of the chapter for measures, standards, or requirements within USP <800> is a strong indicator that those measures, standards, and requirements are opinions, and are not based on scientific evidence. These references appear to be more of a reading list than actual scientifically annotated references supporting standards set forth in USP <800>. Most of them appear to be others’ opinions or writings of the members of the compounding committee, referencing their own opinions as support for the opinions leading to the USP <800> requirements. In some instances, the references note an expectation or finding that has no relevance to the compounding scenario. Opinions do not provide the scientific, evidence-based rigor that the USP delivered in its trademark ingredient standards.
Within USP <800> there are references to other published USP chapters that are built on the same lack of science-based evidence. Some of the references refer readers to informational chapters with 4-digit chapter numbers. The 4-digit USP chapters are not meant to be enforceable, but to provide information. USP <795>, <797>, and <800>, being more opinion than science, should have been published as 4-digit, rather than 3-digit, chapters, but that would not have provided the same reach and revenue opportunities that they currently provide.
These are just a few of the details within USP <800> that make little sense from a scientific perspective.
Without scientific proof of the detailed requirements, no explanation for the one-size-fits-all standards, and no references to individual stated parameters, could USP <800> have been an exercise in creation of an ideal utopia for handling drugs developed by consensus, without consideration for real-world application? Does this really make sense? Why should a series of professional standards chapters be published and pushed onto the healthcare system without representation, proof, or consideration of the adverse consequences that could be triggered? Could it be a simple case of overreaching beyond the parameters of the science-driven mission and value of the USP for the sake of increasing influence and revenue? Is it now time for the healthcare community to stand up and say enough?
USP <800> is outdated, with insufficient scientific evidence presented for its components. This chapter was published on February 1, 2016, following comments, and has not been modified in the 6 years since. At the time, there was little scientific evidence supporting much of the recommendations, and in the Commentary on General Chapter Hazardous Drugs – Handling in Healthcare Settings USP 39 – National Formulary 34, First Supplement published on the same date, the USP responds to several questions about evidence with a statement that there is not yet any published evidence for the standard, but that “the Expert Committee will consider future revisions to this standard once more information becomes available.”4 It is irresponsible to set forth costly standards with an admission that the scientific evidence is not available.
These standards are so far-reaching that one would hope that the creators understood the implications of each requirement. USP <800> is not yet official but has been published since 2016 as if it were inevitable. Some state boards of pharmacy have reviewed the chapter and chosen not to accept or endorse it for lack of evidence supporting the standards. Others have unfortunately blindly accepted what the USP has published and incorporated parts of it in their states. Many hospitals and medical practices have reviewed the standards and questioned how they could possibly afford the cost and disruption of full compliance.
Patients have already lost access to treatments because of compounding changes made in USP <797> (2008 version) that are being carried forward into USP <800>. Many hospital pharmacies chose to stop preparing a first-line standard-of-care treatment for bleeding in bladders. We do not know to this day how many patients went through the trauma of having their bladders removed when bleeding could not be stopped because the authors of the USP <797> (2008 version) decided that a primary treatment now had to be treated as high risk based on their vision of ideal compounding regulations. See my article titled "Alum Irrigation, a Standard of Care, Is Once Again Readily Available for Treatment of Hemorrhagic Cystitis" (page 24) for details on this situation.
Providers in one state were cited, fined, and told to stop treating patients by an overzealous inspection board citing required blind compliance to USP <797> (2008) and USP <800> standards. Their patients missed crucial ongoing treatments because the nearest alternative provider was a 2-hour drive north and it was winter. Eventually, the inspection board realized the impracticality of the rigid standards and these patients are once again receiving needed care in their community medical offices.
With any set of standards, there should be consideration of the impact of compliance versus the impact of noncompliance. It appears that USP <800> was written in a real-world void, not cognizant of the cost of full compliance for the healthcare system and patients. There is a point at which every standard should be measured for common sense risk of compliance and adverse consequences that may arise for either compliance or noncompliance.
Comments have not been accepted on USP <800> since 2016. I believe it is important to write to the USP and clearly state the following concerns regarding this chapter:
The following requests can also be made:
Correspondence can be directed to the USP via Nurisha Wade, Vice President, Healthcare Quality and Safety Center of Excellence, at This email address is being protected from spambots. You need JavaScript enabled to view it..
It is time for the medical community to stand up for their patients, and challenge these standards, which have been presented without scientific rigor or evidence, and which do not consider the risks associated with compliance or the impact on patients. We all want to provide safe, effective care in a manner that is also safe for our staff, but there is no justification for roughshod mandates without scientific justification or common sense in application. Please feel free to reach out to me directly at This email address is being protected from spambots. You need JavaScript enabled to view it. if you have any questions or information.
To sign up for our newsletter or print publications, please enter your contact information below.
