On December 13, 2016, the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD pathway) was added to the Federal Food, Drug, and Cosmetic (FD&C) Act through section 3042 of the 21st Century Cures Act (section 506(h) of the FD&C Act). This pathway provides stakeholders, including FDA and industry, with a tool to help with the approval of antibacterial and antifungal drugs to treat serious and life-threatening infections in a limited population of patients with unmet needs. 

The LPAD pathway, section 506(h)(3) of the FD&C Act, creates two new requirements for drugs approved under this pathway:

 

• specific labeling to let the healthcare community, as well as patients and caregivers, know that the drug was approved under the LPAD pathway, and 
• pre-review of promotional materials for these products.

This new labeling is intended to inform the healthcare community, patients, and caregivers that the product was approved under the LPAD pathway. In particular, the labeling is intended to convey that the approval was based on a benefit-risk assessment that more flexibly considered the severity, rarity, or prevalence of the infection the drug is intended to treat and the lack of alternatives available for the patient population.

Information for Patients, Physicians, and Industry

What is a drug approved under the LPAD pathway?

A drug approved under the LPAD pathway is an antibacterial or antifungal drug approved to treat a serious or life-threatening infection in a limited population of patients with unmet needs. The healthcare community should understand that that the drug has been shown to be safe and effective for use only in a limited population. The labeling of these products define the limited population that the drug is intended to treat so that a health care provider would be able to identify the patients in the clinical setting for whom FDA determined the benefits of the drug outweigh its risks.

What is required for a drug to be approved under the LPAD pathway?

FDA may approve an antibacterial or antifungal drug, alone or in combination with one or more other drugs, under the LPAD pathway, if:

• The drug is intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs;
• The drug meets the standards for approval under section 505(c) and (d) of the FD&C Act or the standards for licensure under section 351 of the Public Health Service Act; and
• FDA receives a written request from the sponsor to approve the drug as a LPAD pathway drug.

See section 506(h)(1) of the FD&C Act.  In this analysis, determining whether a condition is serious is a matter of judgment, but generally is based on whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the condition, if left untreated, will progress from a less severe condition to a more serious one.  See 21 CFR 312.300(b).

The final guidance for industry, Limited Population Pathway for Antibacterial and Antifungal Drugs, describes a limited population of patients for LPAD products as a group of patients limited in such a way as to be clinically relevant to health care providers. The labeling of a product approved under the LPAD pathway product will define the limited population of patients the drug is intended to treat so that a healthcare provider will be able to identify the patients in the clinical setting for whom FDA has determined the benefits of the drug outweigh its risks.

Guidance on the meaning of unmet medical need can be found in FDA’s guidance for industry, Expedited Programs for Serious Conditions – Drugs and Biologics.

How is a drug approved under the LPAD pathway identified?

Drugs approved under the LPAD pathway are required by section 506(h)(3)(A) of the FD&C Act to have prominent labeling stating “Limited Population” on all labeling and advertising. For drugs with a proprietary name, “Limited Population” will appear adjacent to the proprietary name. There will also be similar information in the prescribing information about the limited population for which the drug was approved.

What is the purpose of the LPAD pathway?

FDA believes the LPAD pathway will facilitate development and approval of certain antibacterial and antifungal drugs to treat serious or life-threatening infections in limited populations of patients with unmet needs. We expect that development programs for drugs eligible for approval under the LPAD pathway will follow streamlined approaches to clinical development. This may involve smaller, shorter or fewer clinical trials.

To make fully informed decisions, the healthcare community should understand that approval of a drug under the LPAD pathway was based on a benefit-risk assessment that more flexibly considered the severity, rarity, or prevalence of the infection the drug is intended to treat and the lack of alternatives available for the patient population.

Drugs Approved under the LPAD Pathway

• August 14, 2019, FDA approved Pretomanid Tablets in combination with bedaquiline and linezolid for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs under the LPAD pathway.
• On September 28, 2018, FDA approved the first drug approved under the LPAD pathway, Arikayce (amikacin liposome inhalation suspension), for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC), in a limited population of patients with the disease who do not respond to conventional treatment (refractory disease).

Additional Information

On August 5, 2020, FDA published a Final Guidance for Industry: Limited Population Pathway for Antibacterial and Antifungal Drugs.

On July 12, 2019, FDA held a public meeting to discuss the Draft Guidance for Industry: Limited Population Pathway for Antibacterial and Antifungal Drugs. Comments on the draft guidance can be submitted to the open docket."

On June 13, 2018, FDA published a Draft Guidance for Industry: Limited Population Pathway for Antibacterial and Antifungal Drugs. Comments on the draft guidance can be submitted to the open docket.

For any questions about the LPAD pathway, please contact: druginfo@fda.hhs.gov | Telephone: 855-543-3784 or 301-796-3400 | Fax: 301-431-6353

For information about FDA’s Implementation of the 21st Century Cures Act: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/21stCenturyCuresAct/default.htm.