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Regulatory Focus™ > News Articles > Legislation Hopes to Help FDA ADAPT to Antimicrobial Resistance With New Approval Pathway

Legislation Hopes to Help FDA ADAPT to Antimicrobial Resistance With New Approval Pathway

Posted 13 December 2013 | By Alexander Gaffney, RAC

A new piece of legislation introduced Thursday by a large group of bipartisan legislators would endow the US Food and Drug Administration (FDA) with the ability to approve antibiotic drugs for narrow patient populations based on less stringent standards of approval.


Under current law, with the exception of drugs approved with a Risk Evaluation and Mitigation Strategy (REMS) plan limiting its prescribing, doctors are essentially able to prescribe any drug for any purpose they wish. A drug which has obtained FDA approval for an antipsychotic indication may be prescribed to a patient suffering from bipolar disorder if the doctor believes it could be beneficial, for example.

But for some drugs, off-label usage isn't just individually harmful-it's harmful to others as well. In the case of antibiotics, an incorrectly prescribed drug will not only fail to help a patient, but might also lead to antibiotic resistance in the strain of bacteria, making it more difficult to treat future infections. One has only to look at the proliferation of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals to understand the profound danger to vulnerable patients.

As more and more microbes become resistant to existing antibiotics, regulators have been pressed into making increasingly uncomfortable choices. Some antibiotics could be life-saving for some patients, but carry substantial risks that could make their use untenable for wider approvals, and regulators fear that off-label prescribing could erode those benefits further over time.

ADAPT to Resistance

It is under this backdrop that a group of legislators has introduced the Antibiotic Development to Advance Patient Treatment Act (ADAPT) of 2013. The legislation would modify Section 505 of the Federal Food, Drug and Cosmetic Act to create a new "limited population" pathway for certain antibacterial and antifungal drugs intended to treat serious or life-threatening diseases or conditions.

Any drug approved under the ADAPT pathway-which is itself intended to be an addition to the Generating Antibiotic Incentives Now (GAIN) pathway passed into law in 2012-is intended to be flexible.

Approvals may be based on traditional or alternative endpoints, small clinical trials (including Phase 2 studies), pharmacologic or pathophysiologic data, and "other confirmatory evidence" deemed appropriate by FDA.

The labeling of the drug would also be required to bear a prominent statement: "This drug is indicated for use in a limited and specific population of patients."

Whether or not that statement would have any effect on prescribing habits is perhaps the biggest wildcard. The current legislation would not alter physician authority to prescribe a drug of their choice, though FDA would likely approve any drug under a REMS plan to restrict access or require physician training prior to prescribing an ADAPT product. The law contains a prominent disclaimer that nothing within it is intended to "restrict, in any manner, the prescribing of antibiotics or other products by health care professionals, or to limit the practice of health care."

As with accelerated approvals based on surrogate endpoints, FDA would also be permitted to withdraw the drug or fully approve it at a later date for a larger population, thereby removing its restrictions.

Breakpoints and Reports

In another section of the proposed bill, FDA would be charged with identifying the breakpoints ("susceptibility test interpretive criteria") of antimicrobial drugs, or the point at which a particular dose would be expected to lead to traits of resistance in the bacteria it is intended to treat. This information is especially useful to healthcare professionals to allow for good prescribing practices. Evaluations are expected to take place on a quarterly basis and made public.

The law also contains significant provisions related to monitoring antimicrobial resistance, giving the Center for Disease Control and Prevention (CDC) the charge of monitoring the use of antibacterial and antifungal drugs and resistance to those drugs. CDC data would then be made publicly available at a later time.

Legislators' Statement

FDA Law Blog

Tags: GAIN Act

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