FDA Cracks Down On GLP-1 Imports

By Katie Anderson, Chief Editor, Pharmaceutical Online

An Import Alert (#66-80) has been issued by the U.S. Food and Drug Administration (FDA) to detain GLP-1 APIs manufactured at foreign facilities not approved by the agency. The move is an effort by the FDA to curb the importation of adulterated GLP-1 APIs.

GLP-1 bulk drug substances must be detained without physical examination (DWPE) unless they are on a list (Green List) of approved foreign GLP-1 manufacturers. The “Green List” was developed after evidence was provided to the FDA from manufacturers demonstrating that they meet current good manufacturing practice (CGMP) requirements.

The FDA either physically inspected or conducted remote regulatory assessments of 48 GLP-1 API sites and found that nearly one-fifth were not compliant under section 501 of the FD&C Act. These sites either did not provide the records required to prove that they met CGMP requirements or did not meet those CGMP requirements.

The FDA issued the alert in response to the continual influx of questionable GLP-1 API from overseas sources. Many of these GLP-1 APIs surfaced during the GLP-1 drug shortage, at which time more API was needed for compounded versions.  As demand surged, adulterated products began to proliferate.

Though APIs used in drug products must meet CGMP requirements, the compounders who use those APIs are not required to if they meet section 503A of the FD&C Act. This has put the FDA in a tricky position and the patient potentially at risk.

API manufacturers that wish to make the “green list” must submit records providing information about all GLP-1 API physical manufacturing sites. They must also submit information demonstrating CGMP compliance, which could include:

• Example Certificate of Analysis (COA) that would accompany each lot of API distributed;
• Example labels used on the containers of API that would be distributed;
• List of specifications of the API;
• Scientific justification for each API specification;
• Test methods, including test method validation reports, for each specification, or USP compendial reference (not foreign compendia);
• Names and addresses of any contract laboratories used to conduct release testing;
• Process validation protocol;
• Complete process validation report;
• Example Batch Record;
• List of Equipment used in the manufacture of the API;
• List of SOPs related to the manufacture of the API; and
• Organization chart, including details of the quality unit.

To facilitate review of the submissions, FDA recommends that evidence be submitted in English. Documents not submitted in English will delay FDA reviews.

Monitoring the GLP-1 API that is allowed to be imported into the United States gives the FDA some control over the safety of GLP-1 drugs produced and distributed stateside.