As part of an effort spur the development of new antimicrobial drugs intended for limited patient populations, the US Food and Drug Administration (FDA) on Tuesday issued draft guidance with recommendations for demonstrating the safety and effectiveness of such drugs.
Background & Challenges
In recent years, Congress has attempted to address shortfalls in the development of new antimicrobial drugs as resistance to existing drugs mounts and questions about the economic viability of new antimicrobial drugs loom.
"Despite the growing incidence of…resistant strains of bacteria, there has unfortunately been an overall decline in antibiotic drug research driven largely by the significant obstacles to developing innovations in this category," FDA Commissioner Scott Gottlieb said.
The 2012 Generating Antibiotic Incentives Now (GAIN) Act
, which created the qualified infectious disease product (QIDP) designation, and the more recent 21st Century Cures Act
, which established the limited population pathway for antibacterial and antifungal drugs (LPAD), strive to ease some of those challenges. However, FDA has raised concerns
that drugs qualifying for incentives under the GAIN Act
are often modifications of existing drugs rather than novel ones.
Gottlieb also highlighted reimbursement as a central barrier to development, as reimbursement on a per-use basis runs contrary to effective antimicrobial stewardship, adding that FDA is working with the Centers for Medicare and Medicaid Services and other agencies to develop new reimbursement models for antimicrobial drugs.
One potential model would be for institutions to pay a licensing fee for access to certain antimicrobial drugs, with the goal being to de-link return on investment for antimicrobials from sales volume.
Other hurdles to developing new antimicrobial drugs include difficulty enrolling patients with life-threatening infections who need immediate treatment in clinical trials and challenges in interpreting treatment effects of investigational drugs when patients have already been exposed to first- and second-line treatments.
The guidance comes less than a year after FDA finalized
a separate guidance on streamlined development programs for new antibacterial drugs to treat serious diseases in patients with an unmet need. At the time, FDA noted that some drugs that are candidates for streamlined development would also be candidates for the limited population pathway.
According to FDA, the 14-page draft guidance provides considerations for demonstrating safety and effectiveness for limited population antimicrobial drugs and explains the criteria and processes for using the LPAD pathway.
The guidance also provides recommendations for developing labeling, including prescribing information, patient labeling and carton/container labeling that informs patients and physicians that the product was approved based on evidence from a limited population.
For a drug to qualify for the LPAD pathway, FDA says it must be "intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs," and the product must meet applicable standards for new drug application (NDA) or biologics license application (BLA). Sponsors must also send a written request to the agency requesting the drug be approved as a limited population drug.
When reviewing products under the LPAD pathway, FDA says it will consider the severity, rarity and prevalence of the infection the product is intended to treat and whether there are alternatives that can be used to treat the product's intended population.
FDA also says it will accept greater uncertainty and higher risk for products that qualify for the pathway, and that "drugs with risks that would be unacceptable for a broader population" may be acceptable for serious infections in limited patient populations when there is an unmet need.
However, FDA notes that the pathway is not an avenue for managing known or potential serious risks with a drug and should not be used to salvage a failed trial or inadequate development program. FDA also adds that it will not consider products under the LPAD pathway that could be approved for a broader population.
, Federal Register Notice