Dear All,
I’ve watched with interest the way that FDA’s CVM (Center for Veterinary Medicine) has been working steadily with the veterinary community as a whole to reduce antibiotic resistance pressure by improving the way antibiotics are used in animal care. The titles of these prior newsletters give you a feel for some aspects of the evolving conversation:
- 1 April 2019: “Duration Of Antibiotic Dosing In Veterinary Medicine / Follow-Up Comment On FDA AMDAC On IM Bacitracin”
- 12 October 2020: “FDA Workshop: Revising The Process For Importance-Ranking Of Human Antimicrobials To Guide Their Use In Animals”
- 12 June 2022: “FDA/CVM: Antimicrobial Use In Companion Animals”
With those ideas in your head, we today have a Federal Register notice entitled “Defining Durations of Use for Approved Medically Important Antimicrobial Drugs Fed to Food-Producing Animals (Draft Guidance for Industry).” Here’s the summary blurb (bullets and bold-faced highlighting added to assist with reading):
- The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry (GFI) #273 entitled “Defining Durations of Use for Approved Medically Important Antimicrobial Drugs Fed to Food-Producing Animals.”
- This draft guidance document, when finalized, will provide recommendations on how sponsors may voluntarily establish defined durations of use for certain antimicrobial new animal drugs used in or on the medicated feed of food-producing animals that are currently approved with one or more indications that lack a defined duration of use.
- Establishing defined durations of use within the approved new animal drug applications (NADAs) and abbreviated new animal drug applications (ANADAs) is intended to mitigate development of antimicrobial resistance for these antimicrobial drugs, which are important to human medicine.
- It also, when finalized, will propose timelines for stakeholders wishing to voluntarily align their affected applications with this guidance.
It’s marvelous to see this steady effort. Defining the most appropriate duration of dosing is a challenge in even human medicine, so one must certainly applaud an effort to work on this for animal care.
And if you’d like a bit more, the FR includes a fascinating history lesson regarding the evolution of antibiotics use in animal care. For your convenience, I’ve reproduced it just below my signature.
Well done to our colleagues at CVM! All best wishes, –jr
John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.
== History lesson provided regarding antibiotics in veterinary care ==
This text is copied from the FR; it is also found in the draft guidance.
FDA is announcing the availability of a draft GFI #273 entitled “Defining Durations of Use for Approved Medically Important Antimicrobial Drugs Fed to Food-Producing Animals.” This draft guidance, when finalized, will provide information to sponsors of certain antimicrobial animal drug products who are interested in establishing appropriately defined durations of therapeutic administration to food-producing animals where none currently exist. The draft guidance, when finalized, will also propose timelines for stakeholders wishing to comply voluntarily with this guidance.
In response to recommendations made by FDA in GFI #213, as part of a strategy to address antimicrobial resistance associated with the use of antimicrobial drugs in animal agriculture, sponsors of all NADAs and ANADAs for antimicrobial drugs important to human medicine (medically important antimicrobial drugs) approved for use in or on the feed or in the drinking water of food-producing animals worked with FDA over a 3-year period from 2013 to 2016 to voluntarily withdraw approval of indications that were not considered necessary for ensuring animal health (production indications). In response to FDA recommendations made in GFI #263, sponsors also voluntarily worked with FDA to change the marketing status of all remaining approved uses of such new animal drugs from over-the-counter (OTC) to either by veterinary prescription (Rx) or by veterinary feed directive, as applicable.
In September 2016, FDA announced that it intended to enter the next phase of its efforts to mitigate antimicrobial resistance by focusing on medically important antimicrobials used in animal feed or water that have at least one therapeutic indication without a defined duration of use. In a notice published in the Federal Register of September 14, 2016 (81 FR 63187), the Agency requested comments from the public about how to establish appropriately targeted durations of use for therapeutic products within the scope of GFI #213 with no currently defined duration of use. Public feedback received in response to that request for information was taken into consideration during subsequent development of a concept paper released in 2021.
On September 14, 2018, FDA released a 5-year action plan for supporting antimicrobial stewardship in veterinary settings. This plan includes an action item (Action item 1.1.2 of the 5-year plan) intended “to ensure that all medically important antimicrobial drugs used in the feed or drinking water of food-producing animals have an appropriately targeted duration of use.”
In a notice published in the Federal Register of January 11, 2021 (86 FR 1979), FDA requested comments from the public on a concept paper that outlined a potential framework for how sponsors of NADAs and ANADAs for products containing medically important antimicrobial drugs approved for use in or on the feed of food-producing animals could voluntarily work with FDA to change the approved conditions of use of these drugs to establish appropriately defined durations of use for those indications that currently have an undefined duration of use. The concept paper generated invaluable public comment; FDA considered all information and feedback received on the concept paper as it developed this draft guidance.
This level 1 draft guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on “Defining Durations of Use for Approved Medically Important Antimicrobial Drugs Fed to Food-Producing Animals.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
Current funding opportunities (most current list is here)
- HERA Invest was launched August 2023 with €100 million to support innovative EU-based SMEs in the early and late phases of clinical trials. Part of the InvestEU program supporting sustainable investment, innovation, and job creation in Europe, HERA Invest is open for application to companies developing medical countermeasures that address one of the following cross-border health threats: (i) Pathogens with pandemic or epidemic potential, (ii) Chemical, biological, radiological and nuclear (CBRN) threats originating from accidental or deliberate release, and (iii) Antimicrobial resistance (AMR). Non-dilutive venture loans covering up to 50% of investment costs are available. Applications are accepted on a rolling basis; go here for all the details.
- The ENABLE-2 consortium has announced a call to support hit-to-lead compound development by researchers at publicly-funded European universities. The call is focused on molecules with the potential to be direct-acting therapies for one or more of the following priority pathogens: ESBL-producing/carbapenem-resistant Enterobacteriaceae (E. coli, K. pneumoniae), P. aeruginosa, A. baumannii, methicillin-resistant S. aureus, or vancomycin-resistant E. faecium. The Call is open continuously, applications are reviewed at intervals, and funding is non-dilutive. Expressions of interest received before 30 Sep 2023 would be considered in November 2023. Applications received after this date will be evaluated in the spring of 2024 (date to be decided). Go to https://www.ilk.uu.se/enable2/apply/ for further details.
- The AMR Action Fund is now open to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
- BARDA’s long-running BAA-18-100-SOL-00003 offers support for both antibacterial and antifungal agents. This BAA has offered 4 deadlines/year since 2018 … check the most current amendment for details.
- INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
- These things aren’t sources of funds but would help you develop funding applications
- AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
- The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
- Diagnostic developers would find valuable guidance in this 6-part series on in vitro diagnostic (IVD) development. Sponsored by CARB-X, C-CAMP, and FIND, it pulls together real-life insights into a succinct set of tutorials.
- In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).
Upcoming meetings of interest to the AMR community (most current list is here):
- General note: Virtual meetings are easy to attend, but regular attendance at in-person events is the key to networking and deeper insight. My personal favorites for such in-person meetings are marked below as HIGHLY RECOMMENDED and are the BEAM Alliance’s AMR Conference (March, Europe), ECCMID (April, Europe), the ASM-ESCMID Developer’s meeting (September, alternates sides of the Atlantic), and ID Week (October, USA). Of particular value for developers are the AMR Conference and the ASM-ESCMID conference. Hope to see you there!
- [DON’T MISS THIS ONE!] 27 Sep 2023 (virtual, 10a-11a ET): Milken Institute webinar entitled “What’s Next for the UK’s Subscription Model in the Fight Against Antimicrobial Resistance”. Based on the announcement email from Milken, this will be a deep dive from key UK experts (Sophie Cooper from NICE and David Glover from NHS England) who have been integral to the UK’s thinking. Note also that Milken has published (2022) an excellent deep dive into this area. Go here to register.
- 26 Sep 2023 (virtual or in-person, 1.00-1.50p ET): Webinar entitled “When antibiotics fail: Solving the deadly superbug threat” sponsored by the Harvard School of Public Health. Go here for details and to register.
- 27 Sep 2023 (in-person at BBC Studios, 1120 Avenue of the Americas, New York City 5p ET): Screening (with panel discussion) of “Race Against Resistance: The life and death struggle to save antibiotics”, the fabulous new BBC Storyworks film. Go to https://www.youtube.com/watch?v=5U3k9ruszxI to see the film online; go here to register for the in-person screening.
- 27 Sep 2023 (virtual, 2-3p CET, 8-9a ET): GARDP-sponsored webinar entitled “Antibiotic shortages: causes, consequences and solutions.” Go here to register.
- 4 Oct 2023 (Museum of Science, Boston, MA; in person, 11.30a-2.30p ET): Co-sponsored by the Boston’s Museum of Science and the Rijksmuseum Boerhaave (Netherlands), you can attend a luncheon and panel discussion entitled “Celebrating 300 Years of Innovation and Beyond: How van Leeuwenhoek’s Discovery of the Microworld Sparked a Medical Revolution, with a Focus on Antimicrobial Resistance.” Go here for details and to register. I knew about Boston’s MOS but did not know about the exceptional collection of the Rijksmuseum Boerhaave which seeks to “… show what science is all about: curiosity, guts, creativity and perseverance.” Fascinating!
- 7-15 Oct 2023 (residential, Annecy, France): ICARe, the Interdisciplinary Course on Antibiotics and Resistance. Now in its 7th year, this course is a deep-dive into the world of antibiotic development. Intense, rigorous, and HIGHLY recommended. Seats are always limited … apply sooner rather than later! Go here for details.
- 11-15 Oct 2023 (Boston, USA): IDWeek 2023, the annual meeting of the Infectious Diseases Society of America. Go here for details and to register. HIGHLY RECOMMENDED.
- 12 Oct 2023 (virtual, 2-3p CET) GARDP-sponsored webinar entitled “Market interventions to improve access to antibiotics for resistant infections.” Go here to register.
- 20-23 Oct 2023 (Athens, Greece): 11th TIMM (Trends in Medical Mycology). Go here for details.
- 6-7 Feb 2024 (online): Antimicrobial Chemotherapy Conference. This is an annual, free of charge conference that is co-organized by GARDP and the British Society for Antimicrobial Chemotherapy (BSAC). Details to follow — for now, just mark your calendar.
- 6-7 Mar 2024 (Basel,[NEW] 6-7 Mar 2024): Sponsored by the BEAM Alliance, the AMR Conference is now in its 8th year and is consistently an excellent meeting for developers. You can’t register yet but you can mark your calendar and signup for notifications about the meeting. HIGHLY RECOMMENDED.
- 17-22 Mar 2024 (Ventura Beach, CA, in person): Gordon Research Conference (GRC) entitled “New Antibacterial Discovery and Development” with a 16-17 Mar 2024 pre-conference Gordon Research Seminar (GRS) for young doctoral and post-doctoral researchers. An intensive residential meeting, GRCs are highly recommended for networking and deep research insights. Apply here for the GRC and here for the GRS.
- 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details. HIGHLY RECOMMENDED.
- 26-31 May 2024 (Montreal, Canada): EDAR7, the McGill AMR Centre’s 7th edition of their Environmental Dimension of Antimicrobial Resistance conference. Go here for details; final abstract deadline is 21 Dec 2023.
- 13-17 June 2024 (Atlanta, Georgia): ASM Microbe, the annual meeting of the American Society for Microbiology. You can’t register yet, but you can go here for general details.
- 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. Go here for the meeting’s general website. You can’t register (yet) for the 2024 event, but you can mark your calendar. HIGHLY RECOMMENDED.
