What Pharmacists Should Know About Revised Compounding Standards Becoming Official on November 1, 2023

Pharmacy Times interviewed Selma Mitiche, PharmD, senior scientist for the Compounding Expert Committee at the U.S. Pharmacopeia (USP) within the Healthcare Quality and Safety Collaborative Group on the importance of pharmacopeial standards, and the revised compounding standards becoming official on November 1, 2023 in particular. World Standards Week is October 10 to 12, 2023, so it is a key time to assess preparation for the November 1 official date for the revised compounding standards in USP General Chapters <795> and <797>, as well as the associated standards in USP General Chapter <800> on the handling of hazardous drugs in healthcare settings.

Alana Hippensteele: Hi, I’m Alana Hippensteele with Pharmacy Times. With the official date just weeks away for the latest revisions to the U.S. Pharmacopeia (USP) compounding standards, and World Standards Week upon us this month on October 10 to 12, 2023, now’s a perfect time to reflect on the importance of pharmacopeial standards to the pharmacy profession, and what important new revisions to USP compounding standards mean for pharmacists.

Here with me today to discuss this is Selma Mitiche, PharmD. She’s a senior scientist for the Compounding Expert Committee at USP within the Healthcare Quality and Safety Collaborative Group. She is also a pharmacist by training. Selma, great to have you!

So, remind us why USP pharmacopeial standards are so important, and tell us about your role?

Selma Mitiche: Thank you so much for having me. You mentioned World Standards Week is right around the corner, and it's a great time to recognize the essential role that quality standards play in the global pharmaceutical supply chain. The U.S. Pharmacopoeia is a big part of that.

The standards developed by USP help ensure public health by setting quality expectations for medicines. USP standards exist for everything from the assessment of the quality of raw materials, to the finished product, describing safe manufacturing, packaging, and distribution processes. Many manufacturers and regulatory agencies around the globe use these standards to test for characteristics like identity, purity, and potency. Said simply, you want to be able to trust your medication, no matter where you get it or where it's made. That's the point of standards.

USP is an independent, scientific, nonprofit organization, as you probably know. But the focus here, our real mission, is building trust in the supply of safe, quality medicines. We do that through development of standards. Within USP, my role is senior scientist for the Compounding Expert Committee. We develop standards specifically for compounded preparations. Those include USP General Chapters <795> and <797>, as well as monographs for specific preparations.

I'm involved in all of the work that goes into developing those standards from stakeholder engagement, literature review, and then incorporating all of that feedback and leading the Expert Committee through the process of developing those standards. And then developing the education courses and resources that go along with that.

Alana Hippensteele: Why are compounding standards particularly important?

Selma Mitiche: Think about the tablets you buy at your pharmacy. These are made in a very controlled and validated environment. You're talking about manufacturing here. Every step is controlled and validated. Compounding, on the other hand, is done by a pharmacist, a doctor, maybe a nurse at the bedside. You don't have all of those controls, but you still want to ensure safe and quality preparations. That's the role of these compounding standards.

Millions of medicines are compounded each year to meet the unique needs of patients, say if they're allergic to an excipient, or they don't have access to the right concentration or dosage. Image Credit: © Nadia - stock.adobe.com

Millions of medicines are compounded each year to meet the unique needs of patients, say if they're allergic to an excipient, or they don't have access to the right concentration or dosage. Compounded preparations fill that gap. But the bottom line is, you have to be able to trust that quality medicine, whether it's compounded or not. So, anyone who compounds for humans or animals has to abide by the USP compounding chapters to the extent that the State Boards of Pharmacy adopt those chapters.

The two main chapters we're talking about here, of course, are USP General Chapter <795> for non-sterile preparations and <797> for sterile preparations. These have been revised after 12 years of work by the Compounding Expert Committee. It involved numerous stakeholders. These revisions reflect the latest science. They incorporate over 15,000 public comments from practitioners, industry regulators, as well as patients. Overall, the revisions reflect all the advances in compounding, and they will advance the quality of compounding. This is a big change for the realities of a pharmacy practice and the needs of patients. They’re also a bit more practical. They were published November 1 of 2022, so there was a one-year implementation period, and they become official on November 1, 2023. That's right around the corner.

Alana Hippensteele: What changes in the revised standards are most critical for pharmacists to be aware of?

Selma Mitiche: For <795>, we're talking about changes to the recommendations and requirements for facilities and equipment. There are changes to the minimum frequencies for cleaning, and then some more information about protective garb that personnel wear. The biggest change though has been to the approach for assigning beyond-use dates for compounded preparations. It now uses a more scientifically robust and risk-based approach to assign those beyond-use dates.

For <797>, we've got changes to the labeling requirements, the frequency of environmental monitoring – , so air and surface sampling – and there’s changes to the cleaning requirements. But the main change has been to the way we think about compounded sterile preparations (CSPs). We've moved away from risk levels, and in the current official version we now talk about categories 1, 2, and 3. That's to account for all of the factors that affect the risk and quality of those preparations. The approach to beyond-use dates kind of goes along with those categories. That's also changed, and it's based on a scientifically robust process. It's a risk based approach, and it takes into account not just the environment where the CSPs are made, but all of the specific preparation steps, whether you've used aseptic technique or not, or whether you've sterilized or not.

Overall, the revisions to the chapter reflect advancements in science and clinical practice. We clarified a lot of topics stakeholders said were a bit ambiguous, and we incorporated extensive input from all of the stakeholder engagement that USP conducted.

Alana Hippensteele: Are there unique considerations required for hazardous substances when it comes to compounding?

Selma Mitiche: This is such an important question because when these two chapters, <795> and <797>, become official on November 1, USP General Chapter <800> for the handling of hazardous drugs in healthcare settings also becomes official, or ‘compendially applicable’. That's because those compounding chapters actually reference chapter <800>. In addition to <795> and <797>, the compounding of hazardous drugs has to additionally comply with chapter <800>. It applies to the handling of those hazardous drugs where there's a risk of exposure to the personnel and health care workers. Chapters, <795>, <797>, and other USP chapters, are really focused on the quality of the preparation of the medicine. But here, with chapter <800>, this is the chapter that's protecting that compounder, the pharmacist, or the person behind the counter, and the patient, as well as the environment.

We have standards for how to handle those drugs safely to minimize risk. We are talking here about the requirements for personnel handling the hazardous drugs. We're talking about facility and engineering controls, the procedures for cleaning, decontaminating and deactivating, and what to do in terms of spill control, as well as all the documentation requirements.

There's a point to note here that's really important: If a certain activity, say administration, is out of scope of chapter <795> and <797>, then <800> would not be compendiallyapplicable to that activity. As long as something's within the scope of compounding, then <800> will be compendially applicable. The last point here is that what determines whether a drug is hazardous or not is determined by the National Institute for Occupational Safety and Health (NIOSH), which is part of the CDC. They come up with the list, and they determine which medicines are actually hazardous. Then USP provides standards for how those medicines should be handled.

Alana Hippensteele: That's very helpful. What resources are available to help with the implementation of the revised standards for pharmacists?

Selma Mitiche: I'm really glad you asked this because USP spent a ton of time on this. We realize that there have been extensive changes to these revisions. To support understanding and implementation of the revised compounding chapters and facilitate compliance, we've published several documents with details on all the scientific considerations and the rationale behind these revisions. We also have detailed fact sheets. All of this is available on the compounding pages of the USP website. That's usp.org/compounding. We also have several educational courses on compounding. We've done tons of presentations on the revised chapters at various conferences, and we have our own workshops and annual meetings. Then, regarding hazardous substances in particular, USP also has resources and tools to support the implementation of chapter <800> to advance the public health goal of USP. That includes FAQs, which are also on our website.

Looking ahead, we realized there are some topics that we couldn’t cover in detail in these chapters, and these came up during the revision process of <795> and <797>. Things where stakeholders said, ‘Look, we need more information on this.’ So, we're developing a few resources.They are going to start as Stimuli articles in USP’s Pharmacopeial Forum, which is where we put them for public comment. They are going to cover topics like the development of stability studies for compounded preparations, the application of technology and compounding, enhancing quality assurance and quality control, and the application of aseptic techniques to compounding. These are all articles that are coming up in the future, to give compounders more information to help implement the revisions in the chapters. There's a lot to look forward to there.

Alana Hippensteele: Absolutely, absolutely. Beyond compounding standards implementation, how can pharmacists get more involved in USP’s work to improve global health through quality standards?

Selma Mitiche: We would love for everybody to be involved because really our success at USP is in this mission to improve public health. It’s not just about the staff that's here. Werely on the work of independent expert volunteers. Many of them are trained pharmacists, but we also have folks with other scientific expertise. Any pharmacist seeking more information on how to get involved should check out the USP volunteers webpage. You can also email us at USPvolunteers@usp.org. We will have a call for candidates coming up pretty soon, and that's an excellent opportunity for any person to apply to join a USP Expert Committee.

Pharmacy associations can also engage through the USP Convention, to contribute to either critical dialogue or we can even co-create content around areas of shared priority. Finally, anyone can attend and participate in a USP Expert Committee meeting. Those are posted on our website. And then if folks have any questions about the compounding standards at all, they can send questions to CompoundingSL@USP.org.