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Regulatory Focus™ > News Articles > 2020 > 6 > Antimicrobial approvals are not bottlenecked by FDA

Antimicrobial approvals are not bottlenecked by FDA

Posted 03 June 2020 | By Kari Oakes 

Antimicrobial approvals are not bottlenecked by FDA

Sponsors seeking US Food and Drug Administration (FDA) approval for antimicrobial drugs accessed expedited clinical testing and review programs at least as frequently as those seeking approval of non-antimicrobials, according to a study published Tuesday in The Lancet Infectious Diseases. The median time from investigational new drug (IND) application to drug approval was shorter for antimicrobials than other drugs.
“We did not find evidence that antimicrobial development is more time consuming than non-antimicrobial development or that regulators have been excessively rigid in their approach,” wrote Jonathan Darrow, the study’s first author, and his collaborators. “Rather, clinical testing and review characteristics were similar for antimicrobials and non-antimicrobials,” noted Darrow, of the division of pharmacoepidemiology and pharmacoeconomics at Harvard Medical School, Boston, and his coauthors.
The authors examined all FDA approvals for drugs and biologics between 1994 and 2018. They identified 178 antimicrobial products whose approvals made up 17% of 1,065 drug approvals.
Priority review status was granted to 103 of 178, or 58% of antimicrobials, compared with 402 of 887, or 45%, of non-antimicrobials, a statistically significant difference (P = .0023).
Antimicrobial drugs were also more likely to receive fast-track designation and accelerated approvals: 37% of microbials versus 19% of other drugs were fast-tracked, while 18% versus 9% received accelerated approvals. These differences also were statistically significant (P less than .001 and P = .0046, respectively).
During the study period, 14 drugs were approved under the “animal rule,” where animal studies are used instead of human studies. Of those, nine (64%) were antimicrobials, indicating FDA’s flexibility in antimicrobial approvals, the authors noted.
The median time from IND to approval was 5.9 years for antimicrobials, significantly shorter than the median of 7.6 years for other drugs.
“Overall, 61% of antimicrobials versus 54% of non-antimicrobials benefited from at least one of the principal special development and approval programmes,” wrote Darrow and his collaborators.
Antimicrobials were about half as likely as non-antimicrobials to be granted Orphan Drug Act designation; just 14% of antimicrobials were designated orphan drugs, compared with 30% of other drugs.
In some areas, investigators also found differences between antiviral and antibacterial therapies. For example, systemic antivirals were more likely to be approved through an expedited program than antibacterials. In contrast to the relative maturity of the antibacterial market by the beginning of the 1980s, therapeutic strategies against viruses were severely limited at that time, noted Darrow and colleagues.
The systemic antiviral therapies that were developed to treat HIV addressed a previously unmet need, the investigators said. “Indeed, the HIV epidemic helped to drive the creation of some of the new programs, particularly the fast-track program, which was explicitly modelled on the development of zidovudine,” the first HIV treatment approved in 1987.
Also, most of the antibacterials identified in the study were additions to pre-existing drug classes, making it less likely that sponsors could demonstrate the substantial improvement over existing therapies that is necessary to achieve breakthrough designation.  The authors also noted that antibacterial approvals come on the strength of non-inferiority trials – a study design that also makes it less likely that substantial improvement will be demonstrated.
Darrow and his coauthors noted some limitations, including the fact that only approved products were included in the review. The authors were unable to identify specific dates for INDs and approvals for over a quarter of the products they examined. Finally, the study measured whether specific accelerated FDA programs were used but did not delve into a more fine-grained examination of flexibilities that may have been granted within specific trials.
The study was funded by a Novo Nordisk Foundation grant. The authors reported no conflicts of interest.
Darrow, J. et al. The Lancet Infectious Diseases. Published online 2 June 2020.


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