Advancing Compounding Standards: Insights From the USP Compounding Implementation Workshop

In the fourth annual workshop held at United States Pharmacopeia (USP) headquarters in Rockville, Maryland from September 25 to 26, 2024, on improving the quality of compounding to enhance patient safety through the development of standards for compounded medicines, USP convened a wide range of stakeholders to explore current and emerging stakeholder needs in the compounding realm, focusing on topics of interest since USP General Chapters <795> and <797> became official in November 2023. Pharmacy Times interviewed Selma Mitiche, PharmD, the senior scientist for the Compounding Expert Committee at USP within the Healthcare Quality and Safety Collaborative Group, to learn key insights from the event.

Selma Mitchie, PharmD

Pharmacy Times: What is your perspective on the state of compounding practice today, 1 year after USP <795> and <797> became compendially applicable, and what were some of the key points raised during the workshop?

Selma Mitiche, PharmD: Extensive stakeholder feedback over several years went into the development of the revised <795> and <797> chapters. Since the chapters became official on November 1, 2023, USP has continued to engage stakeholders to support the process of implementation. This has included, for example, presentations and exhibitions on the revised standards at various stakeholder meetings and conferences, responding to a multitude of questions submitted to USP via the CompoundingSL@usp.org email folder, regular updates to the frequently asked questions about documents developed by USP, and publication of several operational considerations documents on the dedicated compounding pages of the USP website.

During the workshop, we heard from participants that they have appreciated these efforts by USP and will continue to utilize the available resources. Preliminary results of surveys conducted by stakeholder organizations showed that there is an increasing level of confidence among stakeholders about their ability to implement the revised standards.

One major challenge raised by workshop participants was the lack of specific recommendations to support the utilization of new compounding technologies to support compliance with the revisions. Technologies mentioned included barcode scanning, automated compounding robots, enhanced workflow management software, image and video capture and processing, etc. Such technologies are becoming increasingly available, particularly in hospital settings. Other challenges included the lack of specific USP standards for parenteral nutrition processing, shortages of competent compounding personnel, and difficulty in finding competent third-party providers of services required to demonstrate compliance with the revised standards. For example, workshop participants mentioned that testing laboratories continue to have long waiting lists to perform stability studies.

Pharmacy Times: What are some approaches raised during the workshop on implementing the compounding requirements internationally?

Mitiche: Pharmaceutical compounding is widely practiced globally but varies significantly in scope among countries. Workshop participants had examples of models of implementation of compounding requirements from Brazil, the United Kingdom, Spain, Germany, the Netherlands, and other European Union countries. In some models, certain countries have highly centralized systems with strict regulations, where compounding is done in large, specialized facilities that serve many pharmacies. Others, however, allow individual pharmacies to compound medications on-site. Participants heard from various presenters that the USP compounding standards are widely used in many countries.

Pharmacy Times: What challenges were raised during the workshop relating to quality assurance models?

Mitchie: Differences in regulations, market size, and health care systems create unique challenges in ensuring consistent quality. For example, various countries may use a variety of pharmacopoeias and quality standards, such that raw materials authorized in 1 country may be prohibited in another. Also, participants discussed the lack of regular updates to some standards and regulations in certain jurisdictions, which can lead to outdated requirements. Therefore, participants underscored the need for global collaboration in quality assurance to facilitate a more harmonized approach across various countries. Finally, participants reviewed a voluntary model of quality assurance implemented in Spain via a collaboration between universities and compounding member organizations.

Pharmacy Times: What were some of the key points raised during the deep dive into special topics on the 2023 compounding chapter revisions?

Mitchie: First, there was a general discussion regarding the implications and subsequent utilization in pharmaceutical compounding of information obtained from certificates of analysis (COAs) commonly provided by suppliers of compounding components. The COAs are reports from the supplier of the results of all analyses performed on the component by the supplier. Chapters <795> and <797> require compounders to understand and interpret this information, and use it when appropriate to make any adjustments during the compounding process. Participants were also made aware of the potential for the existence of other important characteristics of components, which may not be substantiated in COAs, but may nevertheless have significant implications for compounding and, subsequently, product quality and patient safety.

Second, participants also discussed the requirements for Chapter <71> sterility tests, particularly pertaining to compounded preparations. There was a general exploration of <71>, as well as new and emerging alternatives to <71>, based on various technologies. Participants discussed factors to consider when performing sterility testing, such as time to result, limits of detection, and specificity.

Finally, workshop participants explored the implications of the selection of various container closure systems on ensuring the stability and integrity of compounded preparations. Participants considered the need for packaging materials used in compounded products to protect against external influence (eg, temperature, moisture), to prevent biological contamination, to confer safety and compatibility with the compounded product, to protect against physical damage, and to provide space for information and identification (eg, labeling). There was also a detailed discussion regarding the properties of various packaging materials and their ability to confer the factors above. Participants were also introduced to various USP standards that describe requirements for these packaging materials, such as USP General Chapters <381>, <660>, <661>,<662>, <670>, and <671>.

Although not specifically in the deep dive session, we had a presentation on flavoring compounded nonsterile preparations, which is considered compounding under Chapter <795>. The session discussed the challenges associated with using flavors to taste-mask, describing how these are not inert substances but, in fact, chemically reactive substances that can be made up of tens to hundreds of compounds in a single flavor, so the possibility of a chemical interaction with the drug substance is very high. What was interesting is the various alternatives to flavoring that could be used to taste-mask a compounded product, so that presentation was helpful in giving compounders some practical alternatives.