Import Alert 66-80

(Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the manufacturer(s) and/or products(s) at issue. It does not create or confer any rights for or on any person, and does not operate to bind FDA or the public).

Import Alert # 66-80
Published Date: 09/26/2025
Type: DWPE

Import Alert Name:

Detention Without Physical Examination of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Bulk Drug Substances

Reason for Alert:

FDA has approved several Glucagon-Like Peptide-1 Receptor Agonist (GLP-1) drug products for treatment of patients with type 2 diabetes mellitus and chronic weight management for obese and certain overweight patients, along with other indications. FDA is aware that some patients and health care professionals may seek unapproved GLP-1 drug products, such as those containing the active ingredients semaglutide and tirzepatide.

Shortages of approved GLP-1 drug products led to increased compounding of such products using active pharmaceutical ingredients (APIs) from foreign sources. During the shortages, APIs used to compound GLP-1 drug products were supplied by various API manufacturers located around the world, including China, India, and Europe. GLP-1 APIs are drugs as defined by section 201(g)(1)(D) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) because they are intended for use as a component of a drug product and, thus, are subject to current good manufacturing practice (CGMP) requirements pursuant to section 501(a)(2)(B) of the FD&C Act.

Under section 501(a)(2)(B), a drug is deemed to be adulterated when the methods used in, or the facilities, or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformance with CGMP. Moreover, drugs are deemed to be adulterated under section 501(j) if they are manufactured by a firm that delays, denies, or limits an inspection of a facility in which a drug is manufactured, processed, packed, or held, or that fails to provide requested records in advance of or in lieu of an inspection pursuant to section 704(a)(4) of the FD&C Act. Similarly, records provided pursuant to a request under section 704(a)(4) may provide evidence of adulteration under section 501(a)(2)(B).

The Agency has identified specific areas of concern for drugs compounded from GLP-1 APIs that appear to be adulterated. Although API manufacturers are subject to CGMP requirements pursuant to section 501(a)(2)(B) of the FD&C Act, compounders whose drugs meet the conditions of section 503A of the FD&C Act are exempt from CGMP requirements, including the requirement to ensure API used in manufacturing meets specifications for impurities or potency, among other things. Therefore, there is a heightened risk that any quality concerns associated with the bulk drug substance would not be adequately controlled for or monitored during the compounding of finished dosage forms.

Given its concern that GLP-1 APIs used in compounding may be adulterated, FDA has conducted both onsite inspections and remote regulatory assessments of 48 GLP-1 API sites via requests for records or other information under section 704(a)(4) of the FD&C Act to evaluate registered GLP-1 API manufacturers in the U.S. supply chain. Of the
48 GLP-1 API sites FDA evaluated, it found that 21% were noncompliant under section 501 of the FD&C Act, either because their responses to FDA records requests provided evidence of noncompliance with CGMP requirements or because firms did not respond to an FDA records request under section 704(a)(4) in a timely manner. In addition, FDA has encountered a pattern of sites that register as GLP-1 API manufacturers, offer GLP-1 APIs for import, refuse to answer FDA’s requests for records, and then deregister, all within a short period of time.

Based on the information available to FDA described above, foreign-sourced GLP-1 APIs should be considered for detention without physical examination (DWPE) based on the appearance of adulteration. Adulteration puts the safety of the American public at risk.

Guidance:

Divisions may detain without physical examination (DWPE) shipments of GLP-1 APIs offered for entry, except for the products and firms identified on the Green List of this Alert. The Green List, as of the date of initial issuance of this import alert, lists GLP-1 APIs of registered foreign manufacturers whose facilities and associated products, based on FDA’s evaluation of recent evidence, appear to be in compliance with CGMP requirements.

***Release of Articles Subject to Detention Without Physical Examination Under This Import Alert:***

To facilitate review of the submissions, FDA recommends that evidence be submitted in English (original documents should be translated and both the translation and original should be provided). Documents not submitted in English will delay FDA reviews.

***Removal from Detention without Physical Examination (ADDITION TO THE GREEN LIST):***

Requests for removal from DWPE (added to the Green List of this import alert) should include information to adequately demonstrate that the requestor has in place appropriate measures to overcome the appearance of the violation, so that the agency will have confidence that future entries will be in compliance. Examples of such information may include:

Records from the manufacturer providing information about all GLP-1 API physical manufacturing sites, and
Information from the manufacturer demonstrating that the GLP-1 APIs at issue have been manufactured and distributed in compliance with CGMP requirements in section 501(a)(2)(B), and that their drugs are not otherwise adulterated under section 501 of the FD&C Act. This could include:

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

If a firm and/or a representative thereof would like to petition for removal of their GLP-1 API from DWPE under this import alert (i.e., Addition to the Green List), all relevant information supporting the request should be forwarded to the following:

Food and Drug Administration
Division of Import Operations (DIO)
Email to: Importalerts2@fda.hhs.gov.

FDA recommends firms interested in petitioning for removal from DWPE under this import alert provide relevant information prior to shipping drugs subject to this import alert into the U.S. This may help facilitate review and avoid delays at the time of import.

Requests for removal from DWPE (Addition to the Green List) will be referred ***by DIO to CDER/OC/ODSIR/DGDDP/ICB*** for evaluation. For further guidance on removal from DWPE, refer to FDA’s Regulatory Procedures Manual (RPM), Chapter 9-8, “Detention Without Physical Examination (DWPE).”

A firm may be removed from the Green List if FDA has information indicating that the products are no longer manufactured in compliance with the FD&C Act such that future shipments may appear violative.

Questions or issues involving import operations or the submissions of petitions for removal from DWPE should be addressed to OII/DIO (301) 796-0356 or Imports@fda.hhs.gov.

Questions or issues involving science policy, analysis, preparation, or analytical methodology, should be addressed to FDAPRIVATELABIMPORTALERTS@fda.hhs.gov

Questions or issues involving compliance of imported drugs and drug products should be addressed to the CDER Imports Compliance Branch at CDERImports@fda.hhs.gov.

                                                                                                                                                         

List of firms and their drugs that have met the criteria for exclusion from recommendation for Detention Without Physical Examination (DWPE) under this Import Alert (a.k.a. Green List)

                                , BELGIUM
61P[][]72 Semaglutide (Anti-Diabetic)

                           , BELGIUM
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]75 Exenatide (Anti-Diabetic)

                            , CANADA
61P[][]74 Tirzepatide (Anti-Diabetic)

                                               , CANADA
61P[][]72 Semaglutide (Anti-Diabetic)

                                                        , CHINA
56F[][]99 Peptide N.E.C. (Antibiotics), and the importer description contains the word, Retatrutide
61P[][]99 Anti-Diabetic N.E.C. (Anti-Diabetic) and the importer description contains the word, Retatrutide

                                               , CHINA
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)

                                    , CHINA
56F[][]99 Peptide N.E.C. (Antibiotics)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]99 Anti-Diabetic N.E.C. (Anti-Diabetic)

                                        , CHINA
56F[][]99 Peptide N.E.C. (Antibiotics), and the importer description contains the word, Retatrutide
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)
61P[][]99 Anti-Diabetic N.E.C. (Anti-Diabetic) and the importer description contains the word, Retatrutide

                                                              , CHINA
61P[][]74 Tirzepatide (Anti-Diabetic)

                                                 , CHINA
56F[][]99 Peptide N.E.C. (Antibiotics), and the importer description contains the word, Retatrutide
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)
61P[][]99 Anti-Diabetic N.E.C. (Anti-Diabetic) and the importer description contains the word, Retatrutide

                                                 , CHINA
56F[][]99 Peptide N.E.C. (Antibiotics), and the importer description contains the word, Retatrutide
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)
61P[][]99 Anti-Diabetic N.E.C. (Anti-Diabetic) and the importer description contains the word, Retatrutide

                                                   , CHINA
56F[][]99 Peptide N.E.C. (Antibiotics), and the importer description contains the word, Retatrutide
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)
61P[][]99 Anti-Diabetic N.E.C. (Anti-Diabetic) and the importer description contains the word, Retatrutide

                                                     , CHINA
61P[][]76 Liraglutide (Anti-Diabetic)

                                                               , CHINA
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)

                                                          , CHINA
61P[][]76 Liraglutide (Anti-Diabetic)

                                        , CHINA
56F[][]99 Peptide N.E.C. (Antibiotics), and the importer description contains the word, Retatrutide
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)
61P[][]99 Anti-Diabetic N.E.C. (Anti-Diabetic) and the importer description contains the word, Retatrutide

                                                        , CHINA
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)

                                                      , CHINA
61P[][]74 Tirzepatide (Anti-Diabetic)

                                                      , CHINA
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)

                                                , CHINA
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)
61P[][]74 Tirzepatide (Anti-Diabetic)

                             , DENMARK
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)

                             , DENMARK
61P[][]76 Liraglutide (Anti-Diabetic)
61P[][]72 Semaglutide (Anti-Diabetic)

                             , DENMARK
61P[][]72 Semaglutide (Anti-Diabetic)

                                                  , GERMANY
58H[][]06 Dulaglutide (Endocrine-Metabolic Agent)

                                                , INDIA
61P[][]76 Liraglutide (Anti-Diabetic)

                                  , INDIA
61P[][]76 Liraglutide (Anti-Diabetic)

                                          , INDIA
61P[][]76 Liraglutide (Anti-Diabetic)

                                                     , INDIA
61P[][]75 Exenatide (Anti-Diabetic)

                                   , IRELAND
58H[][]06 Dulaglutide (Endocrine-Metabolic Agent)

                           , IRELAND
61P[][]76 Liraglutide (Anti-Diabetic)

                                 , ITALY
58H[][]06 Dulaglutide (Endocrine-Metabolic Agent)
61P[][]74 Tirzepatide (Anti-Diabetic)

                                     , ITALY
61P[][]76 Liraglutide (Anti-Diabetic)

                     , ITALY
61P[][]72 Semaglutide (Anti-Diabetic)

                                    , PORTUGAL
61P[][]72 Semaglutide (Anti-Diabetic)

                           , SWEDEN
61P[][]75 Exenatide (Anti-Diabetic)

                     , SWITZERLAND
61P[][]72 Semaglutide (Anti-Diabetic)

                                                           , TAIWAN
61P[][]72 Semaglutide (Anti-Diabetic)

Product Description:

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Bulk Drug Substances (or Active Pharmaceutical Ingredients [APIs]).

Charge:

For drugs that appear to be adulterated due to Current Good Manufacturing Practice (CGMP) violations:

The article is subject to refusal of admission pursuant to Section 801(a)(3) in that the methods used in and controls used for the manufacture, processing, packing, or holding of drugs and other products do not appear to conform to current good manufacturing practice within the meaning of Section 501(a)(2)(B). [Adulteration, Section 501(a)(2)(B)]


OASIS charge code: DRUG GMPS

Countries

MULTIPLE COUNTRIES

  • (56 F - S 99) Peptide N.E.C., Active Pharm Ingred/Chems for Further Manuf
  • (56 F - T 99) Peptide N.E.C., Active Pharm Ingred/Chems for Rx Compounding
  • (56 F - R 99) Peptide N.E.C., NonSterile Powder
  • (56 F - Z 99) Peptide N.E.C., Sterile Powder
  • (58 H - S 06) Dulaglutide, Active Pharm Ingred/Chems for Further Manuf
  • (58 H - T 06) Dulaglutide, Active Pharm Ingred/Chems for Rx Compounding
  • (58 H - R 06) Dulaglutide, NonSterile Powder
  • (58 H - Z 06) Dulaglutide, Sterile Powder
  • (58 H - S 07) Insulin Degludec, Active Pharm Ingred/Chems for Further Manuf
  • (58 H - T 07) Insulin Degludec, Active Pharm Ingred/Chems for Rx Compounding
  • (58 H - R 07) Insulin Degludec, NonSterile Powder
  • (58 H - Z 07) Insulin Degludec, Sterile Powder
  • (58 H - S 08) Lixisenatide, Active Pharm Ingred/Chems for Further Manuf
  • (58 H - T 08) Lixisenatide, Active Pharm Ingred/Chems for Rx Compounding
  • (58 H - R 08) Lixisenatide, NonSterile Powder
  • (58 H - Z 08) Lixisenatide, Sterile Powder
  • (58 H - S 09) Insulin Glargine, Active Pharm Ingred/Chems for Further Manuf
  • (58 H - T 09) Insulin Glargine, Active Pharm Ingred/Chems for Rx Compounding
  • (58 H - R 09) Insulin Glargine, NonSterile Powder
  • (58 H - Z 09) Insulin Glargine, Sterile Powder
  • (61 P - S 72) Semaglutide (Anti-Diabetic), Active Pharm Ingred/Chems for Further Manuf
  • (61 P - T 72) Semaglutide (Anti-Diabetic), Active Pharm Ingred/Chems for Rx Compounding
  • (61 P - R 72) Semaglutide (Anti-Diabetic), NonSterile Powder
  • (61 P - Z 72) Semaglutide (Anti-Diabetic), Sterile Powder
  • (61 P - S 74) Tirzepatide (Anti-Diabetic), Active Pharm Ingred/Chems for Further Manuf
  • (61 P - T 74) Tirzepatide (Anti-Diabetic), Active Pharm Ingred/Chems for Rx Compounding
  • (61 P - R 74) Tirzepatide (Anti-Diabetic), NonSterile Powder
  • (61 P - Z 74) Tirzepatide (Anti-Diabetic), Sterile Powder
  • (61 P - S 75) Exenatide (Anti-Diabetic), Active Pharm Ingred/Chems for Further Manuf
  • (61 P - T 75) Exenatide (Anti-Diabetic), Active Pharm Ingred/Chems for Rx Compounding
  • (61 P - R 75) Exenatide (Anti-Diabetic), NonSterile Powder
  • (61 P - Z 75) Exenatide (Anti-Diabetic), Sterile Powder
  • (61 P - S 76) Liraglutide (Anti-Diabetic), Active Pharm Ingred/Chems for Further Manuf
  • (61 P - T 76) Liraglutide (Anti-Diabetic), Active Pharm Ingred/Chems for Rx Compounding
  • (61 P - R 76) Liraglutide (Anti-Diabetic), NonSterile Powder
  • (61 P - Z 76) Liraglutide (Anti-Diabetic), Sterile Powder
  • (61 P - R 99) Anti-Diabetic N.E.C., NonSterile Powder
    Desc: Anti Diabetic N.E.C. (Anti Diabetic) and the importer description contains the following word; Custom Peptide
  • (61 P - S 99) Anti-Diabetic N.E.C., Active Pharm Ingred/Chems for Further Manuf
    Desc: Anti Diabetic N.E.C. (Anti Diabetic) and the importer description contains the following word; Custom Peptide
  • (61 P - T 99) Anti-Diabetic N.E.C., Active Pharm Ingred/Chems for Rx Compounding
    Desc: Anti Diabetic N.E.C. (Anti Diabetic) and the importer description contains the following word; Custom Peptide
  • (61 P - Z 99) Anti-Diabetic N.E.C., Sterile Powder
    Desc: Anti Diabetic N.E.C. (Anti Diabetic) and the importer description contains the following word; Custom Peptide