USP Expert Discusses Revisions to Compounding Chapters <795>, <797>

Pharmacy Times interviewed Brian Serumaga, PhD, senior manager - personalized medicine at US Pharmacopeia (USP) on details of the revisions to compounding chapters that were published on November 1, 2022. The chapters updated included <795> Pharmaceutical Compounding - Non-sterile Preparations and <797> Pharmaceutical Compounding - Sterile Preparations.

Alana Hippensteele: Hi, I’m Alana Hippensteele with Pharmacy Times. Joining me is Brian Serumaga, PhD, senior manager - personalized medicine and a pharmacist by training at US Pharmacopeia, or USP, who is here to discuss details regarding the revised compounding chapters.

So what has been your role in the process of revising these compounding chapters at USP?

Brian Serumaga: So thanks, Alana, and thanks very much for the invitation to speak to the audience of Pharmacy Times.

Well, firstly, I think it's important to explain to the audience that USP staff act as liaisons for the expert committees. So I'm sure as many of your audience know, USP works through expert committees and the expert committees are composed of independent volunteers from various fields of practice who offer their time to help us set standards.

So the liaison role includes several activities, and I won't list all of them but think about it as ensuring that the expert committee work plan gets implemented on time and as agreed upon by the Council of Experts that actually designs the work plan for each expert committee. So this includes, for instance, convening regular meetings of the expert committee, and making sure that before those meetings happen, the expert committee members have clear and relevant briefing materials. USP staff also plays a role in external communications with stakeholders—collecting feedback and participating in events such as this interview.

I would like also to point out, Alana, that USP staff, although they participate in the meetings of the expert committees, do not actually play any role in determining the final content of the standards. So this means USP staff do not actually vote on any of the ballots that the expert committee members have as they are determining the final content of the standards.

Alana Hippensteele: Interesting. What are the new standards for?

Brian Serumaga: Yeah, so this is a good question. USP’s standard setting process is really robust, and it takes into account stakeholder input. Now the standards that we're talking about here are 2 general chapters <795> Pharmaceutical Compounding - Non-sterile Preparations and <797> Pharmaceutical Compounding - Sterile Preparations. So, as the titles say, these chapters are for compounding of non-sterile and sterile medicines.

So I think the next question you're probably going to ask is what is compounding. So compounding really entails the combining, the mixing, and the altering of ingredients by usually a licensed pharmacist, but not always—it could be a physician, it could be a nurse, it could indeed be any other health care practitioner. And this is intended to create a drug that meets the unique needs of an individual patient.

So, as you can imagine, compounding provides patients with medicines when they may not be able to take a conventionally manufactured drug. And this is actually a very common scenario, for example, for patients who have an allergy to an ingredient in a conventionally manufactured drug, and they need that medication reformulated without that ingredient.

It's also common for certain special groups. For example, as you can imagine, a newborn baby who may not be able to swallow a tablet or capsule would need that medication reformulated maybe into one oral liquid that they could easily take. So that's what these chapters are for.

Alana Hippensteele: Right, that's really interesting. What are some of the changes that are included in these chapters?

Brian Serumaga: Yes. So maybe I should start by talking about the changes that are common across both chapters, and then maybe I'll talk about what's unique in each of the chapters.

So first of all on what's common—readers of both chapters will see that there is now additional information in there to explain topics that are frequently misunderstood, or topics that USP gets lots of questions from stakeholders about. So the expert committee took their time to actually put that information directly in the chapter, either in terms of a clarification or just additional information for readers to be aware of.

Also, readers will see that the chapters are now sectioned out, and topics that are frequently performed in actual practice together or that are related are actually grouped in these new sections. So this obviously helps with navigation of the chapters, but also hopefully with implementation.

So, now let's talk about <795> Pharmaceutical Compounding - Non-sterile Preparations chapter. So, when readers look at this, they will actually see a number of changes pretty much throughout the chapter, but mainly in 2 areas: One in the facilities and equipment section, and also in the minimum frequencies for cleaning. And you will see information in there around what is actually required to clean the various areas that compounders actually deal with when they are preparing non-sterile preparations. There is also now also information on protective garb and personnel wear.

Then in <797> Pharmaceutical Compounding - Sterile Preparations, readers will see updates around requirements for facility design. This is actually a very big topic for combining sterile preparations because, as you can imagine, the design of the facility is a key component in actually achieving a state of control and subsequently achieving this thorough preparation during the compounding process. So in tandem, there is also a number of changes in the frequency and type of environmental monitoring, and there is more information on the core competencies for personal training and competency evaluation.

A big change for both chapters is in the beyond use dates. So, in both chapters, there is now a scientifically robust and risk-based approach to assign beyond use dates--beyond use dates being that date after which a compound in preparation must not be used.

So in <795>, readers will see that the beyond use dates are now referred to as limits, and there is additional information on several physical chemical parameters that compounders need to consider when they're assigning beyond use dates for non-sterile preparations. One of which, for example, is water activity.

In <797>, readers will see a major change in the way compounding sterile preparations are classified. So, the expert committee has now moved away from a classification of low, medium, and high-risk categories to now category 1, category 2, and category 3 components to our preparations. And this question is really based on the level of control that a compounder has of their environment, as well as the process of compounding, and subsequently, the duration of the beyond use dates that they can actually assign.

Readers will also see that actually this new approach, in some instances, allows for longer beyond use dates. So in tandem with stakeholder engagement feedback that the expert community received, they also consider the need to protect patients and also the actual circumstances that folks engaging pharmacy practice find themselves in. So these I think are the main changes that readers will see.

Alana Hippensteele: Right. Could you explain further, why are these chapters being updated now? Why is it important this year?

Brian Serumaga: Yes. So I think the first thing to say on this, Alana, is that USP has actually been working on revisions to <795> and <797> for over 10 years now. So during this time, various versions of the combining expert committee, over 3 cycles, have worked on drafts of these chapters. And the chapters have actually been out for 3 rounds of public comments. And during those public comment periods, they have received a total of over 10,000 comments. So, over time, the expert committees have been working on reviewing all those comments and actually finalizing the chapters.

So then the question you asked is why now? So, as you can imagine, science and clinical practice are not static fields, they actually do change, and, subsequently, combining medicine standards also need to evolve in tandem. So USP standards are based on the current scientific evidence, and because of that, they undergo constant revision to ensure that they are up to date. So the idea here is to actually bring both <797> and <795> up to date with the latest information and scientific evidence as well as stakeholder feedback and scientific opinion from various experts.

Alana Hippensteele: So why are publishing the standards important rather than potentially just establishing them as the standard practice?

Brian Serumaga: Yeah. So as you can imagine quality standards for compounding medicines helps to really protect patients and personnel because adhering to standards reduces several untoward effects, things like sub-potent or super-potent or contaminated medications from actually getting to the public. So USP’s compounding general chapters establish procedures and methods for practitioners to consistently follow so that they can subsequently consistently produce high quality compounding preparations. And again, like I said, this helps promote patient safety.

I think also, one thing to add to this, Alana, is that USP has been producing compounding standards, really since its founding over 200 years ago now. So USP has been in this space for quite a while.

Alana Hippensteele: And what is USP’s process for updating these chapters? You mentioned it's been a 10-year process. What does that look like?

Brian Serumaga: Yes. So again, I mentioned earlier that USP works through independent volunteers who constitute the expert committees that draft and finalize our standards. So for the compounding chapters, USP does have a compounding expert committee that has been working over the last 3 cycles. The current compounding expert committee, for instance, consists of 15 members from various disciplines, including health care practitioners who have expertise in things like sterile and non-sterile compounding, veterinary compounding, aseptic technique, microbiology, environmental engineering, analytical testing, so quite really a diverse range.

Additionally, these expert committee members are joined by 6 government liaisons who participate as non-voting members of the expert committee. And so for the compounding expert committee, there are currently 4 representatives from the FDA, and then 2 from the CDC. And these together constitute the expert committee.

So once that committee has created a draft chapter, that draft is actually published in a free USP publication called the Pharmacopoeia Forum for a period of public comment that is not less than 90 days. It has actually been extended many times for various standards, such as was the case for <795> and <797>. But that period of public comment cannot be less than 90 days.

So the expert committee then considers the input from all of the stakeholders, as well as scientific evidence, and they may also consult with various experts out in the field to form the final versions of the chapters. When these final versions are available, they are then published in the USPNF, the United States Pharmacopoeia National Formulary.

I would like to mention, Alana, that specifically for compounding standards, stakeholders can also access them through a subscription to the compounding companion, which is a selection of the compounding specific standards in the USPNF.

Alana Hippensteele: That's really interesting. When do the new standards go into effect?

Brian Serumaga: Yes. So typically, when USP standards are published, there is a minimum of a 6-month implementation period. Now for the revisions to <795> and <797> that were published on November 1, 2022, the implementation period is actually 1 year.

So the compounding expert committee voted to extend the implementation period by one year. And this extended timeline is hopefully going to enable stakeholders to implement the chapters and put in place all the additional sort of levers and things they actually need to do to be able to comply with the chapters. As always, USP encourages early implementation. And we are always ready to help out as and when requested to do so.

Alana Hippensteele: Right. What resources are available to help with the implementation of the revised chapters, and will those resources still be available on into the future?

Brian Serumaga: Yes, that's a great question. I'm glad you asked that, Alana.

So, USP does actually have quite a number of resources. Most of them are available on the compounding pages of the USP website. So the website is usp.org/compounding, so www.usp.org/compounding.

So, maybe let me just give you a couple of examples. So USP has a USP <795> and <797> FACT Sheet, and this fact sheet really just lays out broad strokes of the major changes in the revision, so that readers are aware of where to look for major changes when they're reading the chapters.

I said earlier that USP receives comments. So when we publish a chapter, such as this one, USP produces a document called the commentary. So for both of the chapters, for <795> and <797>, on the website, readers will be able to access the commentary. And the commentary is a summary of all the expert committee comments and the deliberations that they actually had while they were reviewing all those comments. I would really encourage readers to consider reading the commentary in tandem with the chapters because the commentary will give readers a good idea of what the expert committee was considering when they were writing the various sections in the chapter. And to be able to do that we have actually made sure that the commentary sections match the sections in the chapter itself.

So also, I would like to advertise if I may, Alana, the compounding workshops that USP has coming up. So on February 7 and February 8, 2023, USP will be hosting implementation workshops at our headquarters in Rockville, Maryland. We do hope that that event will be in person. So when the registration opens, please consider registering to participate in person. But we will also have virtual options. So look out on the USP website. And you can actually sign up on USP’s website for updates if you'd like to be kept abreast of our preparations for those workshops.

We also always have educational offerings. So we do have live courses with speakers out every fall and every spring through our USP Education Office. And those are available for sign up on the USP website.

We do have e-learning options as well. So if you are unable to come to USP for those educational courses, you can certainly partake through the e-learning options that are available on-demand.

Finally, I'd also like to mention that USP staff and expert committee members will be out speaking nationally, and also at regional conferences and exhibitions on the standards. So please look out for USP sessions at upcoming national and regional conferences that stakeholders typically attend.

Editor’s Note: The public can email questions about these compounding chapters revisions to compoundingSL@usp.org.