Fast-tracking innovations to treat drug-resistant infections by strengthening regulatory frameworks
Between the 1940s and 1960s, there was a boom in antimicrobials development, particularly, after the discovery of Streptomycin. The antimicrobial managed to cure some life-threatening infections and decreased the mortality rate drastically. After the serendipitous discovery of initial antibiotics like penicillin, pharma companies improvised on the extraction and isolation of molecules and produced over 20 new antimicrobials in a span of three decades. Unfortunately, the discovery rate decelerated after the 1960s as the microbes started to develop resistance rapidly to these antimicrobials.
While growing resistance is one of the major contributing factors why AMR innovations have taken a hit to progress, lack of novelty, slower clinical uptake, confounding regulatory landscape, and lowered market entry are further adding to the lack of a strong drug pipeline. Innovative economic models like ‘push’ and ‘pull’ incentives are pursued but streamlining regulatory mechanisms can further drive the innovations.
Regulatory Barriers Faced for the development of new antibacterial and diagnostics
The lack of standards for the development of novel antibiotics, and the cost of clinical trials are the major regulatory roadblocks faced by the innovators in developing new antimicrobials. The estimated cost is around 130 million US Dollars for a drug candidate to progress from Clinical Phases I to III [O’Neill J. (2015a]. An added challenge is in recruiting patients for clinical trials due to the short treatment window period and lack of access to the appropriate point of care diagnostic tools.
The challenges don’t end here. An antimicrobial is considered a successful innovation when it has gained market approval. But the differences in approval procedures of drug regulatory agencies in various geographies, make the entire process laborious and expensive. The differences are apparent across various parameters like patient selection criteria, definitions of clinical end-points, rules regarding expedited approval, and so on. Due to a lack of regulatory harmonization between countries, there is duplication of effort and greater costs associated with delivering medicine to the market.
For effective use of new antimicrobials and stalling the resistance development, diagnostics play a pivotal role. Companion Diagnostics show is a promising approach to improve the antimicrobial development process and better understand its efficacy on patients. But the regulatory approval of the corresponding diagnostics tests in association with the antimicrobial has proven challenging. As per the FDA guidelines, both the diagnostic and the therapeutic product need to be approved simultaneously. A delay in the approval of one could hinder the progress of the other product. The development process of the antimicrobial and the diagnostic is usually not aligned and additional time may be needed in choosing the companion diagnostic. Very rarely has a therapeutic received approval where the company has made a commitment to developing a companion diagnostic in stipulated time.
Resolving the bottlenecks
AMR-specific streamlined regulatory pathways and incentives can facilitate new and emerging antimicrobials. Based on the objective of antimicrobial usage, the regulatory process can be expedited.
For instance, European Medicines Agency (EMA) antibiotics that are used against rare pathogens or address unmet medical needs can go under special categories like orphan drug designation or can be approved using abridged data based on a risk-benefit analysis.
Collaboration and data sharing between regulators can greatly help in aligning and streamlining pathways. For example, EMA, FDA, and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) have agreed to harmonize their data requirements for certain aspects of clinical trials for new antibiotics. International harmonization is a great way of learning how the global pathways could be adapted to individual nations.
Newer molecules like antimicrobial peptides and bacteriophages are explored as antimicrobials. Clear regulatory guidelines must be in place for such antimicrobials.
Periodic revision of guidelines based on scientific advances and tools can bring efficiency and cost reduction in the drug development process.
Additional regulatory incentives include an expedited review process, combining diagnostics with antimicrobials [companion diagnostics], stronger market or data exclusivity provisions, registration fee waivers (which could improve the cost structure for small businesses), and could accelerate the entry of new antibacterial into the market.
Conclusion
Aligning and harmonizing regulations across countries eases the process of regulatory approval, brings in greater efficiency, and reduces cost. This does not necessarily mean a uniform regulatory system globally, but rather one that adapts and optimizes a framework taking into consideration national factors.
Disclaimer: The blog is a compilation of information on a given topic that is drawn from credible sources; however, this does not claim to be an exhaustive document on the subject. It is not intended to be prescriptive, nor does it represent the opinion of C-CAMP or its partners. The blog is intended to encourage discussion on an important topic that may be of interest to the larger community and stakeholders in associated domains.
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