Amy Cadwallader, PhD, director of Regulatory and Public Policy Development at US Pharmacopeia (USP), discusses how medicine quality and the medicines supply chain can affect antimicrobial resistance (AMR).
Pharmacy Times interviewed Amy Cadwallader, PhD, director of Regulatory and Public Policy Development at US Pharmacopeia (USP), on the impact of antimicrobial resistance (AMR) on medicine quality and the medicines supply chain.
Alana Hippensteele: Hi, I’m Alana Hippensteele with Pharmacy Times. Joining me is Amy Cadwallader, PhD, director of Regulatory and Public Policy Development at US Pharmacopeia, or USP, who is here to discuss the impact of antimicrobial resistance, or AMR, on medicine quality and the drug supply chain.
So, Amy, can you tell us a bit about your role at USP?
Amy Cadwallader: Sure, Alana, and thanks for having me. I am a pharmacologist and analytical toxicologist by training and I'm relatively new to the USP team, having joined at the beginning of this year. Prior to that, I lead drug and science policy activities at the American Medical Association. In my role here at USP, I really lead the development of evidence-based policy positions and related content. I also foster relationships with key stakeholders such as pharmacists.
Alana Hippensteele: So the stats about the impact of AMR are staggering. Can you talk about this a bit?
Amy Cadwallader: So certainly. Antimicrobial resistance, or AMR, occurs, as the audience knows, when microbes such as bacteria or viruses evolve and change, and this change causes the medicines that we use to kill their infections to be less [effective] or ineffective. In the United States, it’s reported that over 2.8 million AMR infections occur every year leading to over 35,000 deaths.
The World Health Organization has deemed AMR one of the top 10 public health threats facing humanity today, and in an alarming recent publication, it was estimated that in 2019, over 1 million people died worldwide due to AMR infections, and another 5 million people died because of complications from them. The paper also notes that if we don't take immediate action that by 2050, there could be over 10 million deaths due to AMR every year. And I should also note that the leading cause of AMR is over and inappropriate use of some of these antimicrobial medications.
Alana Hippensteele: How does medicine quality affect AMR?
Amy Cadwallader: Sure, medicine quality can contribute to AMR in 3 primary ways. The first is the amount of the active pharmaceutical ingredient, or API, in the medications. It can be less and cause patients to take a sub-therapeutic dose.
The second is poor quality excipients or inactive ingredients. If these are present in the medications, they can change the pharmacokinetics of the drug and it can act inappropriately or ineffectively in the human body. The third is from impurities or degradation products that that appear in some of the medications, this can also cause a subtherapeutic dose.
I should also note that all 3 of these quality issues drive a process called selective pressure, where the microbes’ exposure to a moderate dose kills the weaker microbes, but those that are stronger, thrive and propagate at a higher rate.
Alana Hippensteele: That's fascinating. So what is the pharmacists role in combating AMR?
Amy Cadwallader: Sure, 2 primary things come to mind. The first is encouraging stewardship, and that means talking to patients about adhering to the course of their medications and finishing all of it.
The second really is ensuring quality, making sure that there's appropriate storage at the pharmacy and also having those conversations with patients about storing the medication appropriately at home. They can also talk with patients about not saving any leftover medications and properly disposing of it, because expired medications, especially antimicrobials, have a lower potency and that subtherapeutic dose can propagate resistance.
Alana Hippensteele: So what is USP’s role in addressing AMR?
Amy Cadwallader: So, thanks for asking. USP is taking a multifaceted approach to addressing antimicrobial resistance. The first is really to better understand the issue and how quality affects it. USP has a quality institute that sponsors independent research that answers evidence-based policy questions and really informs our policy development, and the USP Quality Institute has sponsored research looking at how medicine quality affects antimicrobial resistance.
Second, we have many public quality standards related to the manufacturing of antimicrobials. Third, we're looking at supply chain vulnerabilities and how to address them to shore up the supply chain for an adequate supply of these medications. And finally, we are engaging in a lot of dialogue talking about stewardship issues and also innovation so that we continue the pipeline of new and novel antimicrobials.
Alana Hippensteele: Right. How does the medicine supply chain effect AMR?
Amy Cadwallader: Sure, thanks. That's a really great question. USP recently highlighted some data from an analytics tool, we have the medicine supply map, and those data indicate that antimicrobial medications are 42% more likely to go into shortage than other medications. When drugs go into shortage, there tends to be a proliferation of falsified and substandard medications in the supply chain, and while those implications mainly affect lower- and middle-income countries, the implications really are global and in the propagation of antimicrobial resistance. So we're encouraging broader geographic distribution of API manufacturers and more sources of manufacturing of those active pharmaceutical ingredients. We're also encouraging appropriate storage along the supply chain.
Alana Hippensteele: Right. What are some things we should do to address AMR, and how can USP and pharmacists work together to do so?
Amy Cadwallader: Sure, pharmacists are really important touch points for patients and patients really listen to the advice that they receive from their pharmacists. So I would just like to highlight that it's really important that pharmacists have those conversations with their patients about adherence and about storage issues. USP and pharmacists have worked so closely together for over 200 years since we've been established and hearing the input observations and the challenges that pharmacists are facing on the front lines really helps inform our work and can help us to better help all the stakeholders including pharmacists.
Alana Hippensteele: Right, absolutely. Anything else to share?
Amy Cadwallader: No, I really think that the big takeaway message here is that we all need to be better stewards of antimicrobial medications to ensure that the supply we currently have remains effective as we're continuing to innovate. I also think that understanding why and how quality really does matter for this issue is important. So if folks want to learn more, they can check out usp.org or any of the links that we've provided.