January 1 was more than just the start of a new year for USP in 2018. It was the implementation date of two new standards designed to safeguard the global drug supply from potentially toxic impurities – mercury, cadmium, arsenic, and lead, for example.
Known as General Chapters <232> Elemental Impurities—Limits and <233> Elemental Impurities—Procedures, these standards were the result of a thirteen-year effort, spearheaded by a team of global scientific experts who volunteer at USP to set standards that help ensure the medicines we take are safe.
At the forefront of this effort from start to finish was Nancy Lewen, a longtime USP volunteer with thirty years of experience in the pharmaceutical industry, most recently as a research fellow specializing in atomic spectroscopy techniques. Recently, Nancy sat down with us to share her insights on the work that went into developing these new standards, as well as her experiences as a USP volunteer expert.
Q: When and how did you get involved in the USP standards development process?
A: In 2004, my laboratory published a paper on an inductively coupled plasma-mass spectrometry (ICP-MS) method that detailed a side-by-side comparison with the USP test for heavy metals that was official at that time. USP had begun talking about replacing Chapter <231> Heavy Metals, which had not been significantly updated since it was created in the early 1900s. Knowing that our ICP spec method could be an applicable and beneficial alternative to that standard, I began participating on a related USP Working Group.
It didn’t take long to realize that partnering with USP provided a unique space for possibly advancing the technique for industry. In 2005, I officially became a USP volunteer expert, first on the USP Elemental Impurities Advisory Panel, then I began chairing the subsequent USP Elemental Impurities Expert Panel. I’ve also been a member of USP sub-committees on pharmaceutical waters, spectroscopy, and modernizing <191> Identification Tests. I am the current chair of the 2015-2020 USP General Chapters—Chemical Analysis Expert Committee.
Q: You chaired the Elemental Impurities Expert Panel for more than a decade. What kept you inspired to stay involved?
A: I knew it was critical that we got the new standards scientifically correct within the context of the work for them to meet the needs of patient safety, first, then USP and industry. Labs around the world would need to be able to follow any new methods we came up with. So, everything we did needed to make scientific sense and be practical. There was no time limit on getting it right.
Another incentive was the opportunity to work with and share ideas with the group. As chair, part of my role was to make sure we had the right mix of expertise to accomplish these objectives. We started predominantly with analytical chemists and added toxicology experts as our work evolved. Several years into the effort, the International Conference on Harmonization (ICH) jumped in—which later led to harmonizing the new standards with ICH Q3D. This gave us further validation that we were on the mark with what we were doing.
I can’t stress enough the incredible level of expertise that contributed to the panel. From Tim Shelbourn, M.S., who was by my side from day one; Helmut Rockstroh, Ph.D., who always kept us focused on answering the questions that need to be answered; and Mark Schweitzer, Ph.D., our industry representative for ICH Q3D…to the many, many others whose dedication made the chapters happen. Plus, our amazing USP liaison Kahkashan Zaidi, Ph.D. She shepherded us through the process wonderfully, always pointing to areas where we needed to validate our work by giving scientific reasons why we could or couldn’t do X, Y, and Z.
During discussions, we could be from opposite ends of the world, opposite ends of every potential viewpoint imaginable, and we would talk the science. It was interesting and fun and meaningful. What we came up with was better because of the sum of the parts contributing rather than just one person or entity. And it was all because of USP and how they provided this opportunity and facilitated the standards-setting process.
Q: How do the new standards benefit public health?
A: The new standards provide more meaningful scientific data that can be used to identify the presence of specific elemental impurities and inform potential impact of the drug product on patient safety. The former heavy metals test lacked quantitation and specificity, which meant you could get a positive result but not know which heavy metal caused it.
Chapter <232> specifies the list of elements and their toxicity limits, defined as maximum daily doses of different drug categories, such as oral, parenteral, inhalation and large volume parenteral. Chapter <233> deals with the analytical procedure, sample preparation and instrumental method for measuring the elements, including the choice of two plasma-based spec techniques: inductively coupled plasma atomic emission spec (ICP-AES or ICP-OES) and inductively coupled plasma mass spec (ICP-MS).
With these new standards, we’ve moved the analytical procedures to modern times, reflecting modern knowledge that’s applicable to modern medicines. Plus, the new standards provide analysts with flexibility to use any analytical procedure they choose, as long as it meets the validation criteria. There is no need to buy new equipment if what they have is already working, which can help control laboratory costs.
Q: What advice do you have for those considering USP volunteer expert opportunities for 2020-2025?
A: Do it. It’s worthwhile. It’s interesting. It stretches your mind differently than what you would do in your day job. In my former day job, it was developing the methods, validating the methods, running the samples. Here at USP, it’s continuously asking what impact does developing the method this way and validating it this way have anywhere, in any lab in the world? You have to consider that whatever you are doing has to be able to be done anywhere, by anybody, on any sample. You learn as you share with the other scientists. It helps you to think beyond your own four walls.
Learn about opportunities for volunteering your expertise at USP
Developing standards for methods of chemical analysis, like those for elemental impurities, is just one of many opportunities at USP for scientific and healthcare professionals – whether early career or seasoned experts – to volunteer their expertise and make a lasting impact on quality medicines and public health. In preparation for the start of the 2020-2025 business cycle, USP is currently seeking new volunteer applicants. Pharmaceutical scientists, academicians, regulatory professionals, healthcare practitioners, and others who work with medicines, dietary supplements and foods are encouraged to apply.
Learn how you can play a role in creating a healthier tomorrow or follow Volunteering at USP on LinkedIn.