Call for Data: Stakeholder Input on Pharmacopeial Forum PF 52(1) Drug Monographs

Call for Data: Request for Stakeholder Information Related to Pharmacopeial Forum (PF) 52(1)

Type of Notice: General Announcement
Posting Date: 24-Apr-2026
Input Deadline: 1-Jul-2026

In accordance with the General Announcement FDA Stakeholder Engagement Requests for Small Molecules PF Proposals, this is to share comments received from the US FDA in regard to revision proposals presented in PF 52(1), where the Agency is recommending that USP engage with stakeholders to obtain additional information regarding the following revision proposals:

• (REF: 03-26-005-Z)
• (REF: 03-26-002-Z)
• (REF: 03-26-010-H)
• (REF: 03-26-007-H)
• (REF: 03-26-006-H)
• (REF: 03-26-009-H)
• (REF: 03-26-003-Z)
• (REF: 03-26-004-Z)
• (REF: 03-26-008-H) Data and/or FDA approved specifications may be submitted to USP by contacting the USP Donations Program at Donations@USP.org. As applicable, USP will require the FDA approved application number associated with any data provided.  In addition, please include chemical information for any impurities or degradation products submitted.

See the following links for additional information on USP’s Donation Program:
Contribute to New or Revised USP Standards
USP Revision Request Form

Specific details for each revision proposal are provided on subsequent pages below:

Call for Data: Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution (REF: 03-26-005-Z)
USP published a revision proposal for Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a new monograph for this drug product.
USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

1. In the IMPURITIES section,
   1. We note that the acceptance criteria for “Total degradation products for Brimonidine Tartrate”, “Hydroxythiadiazol sulfoxide derivative”, “Timolol related compound B”, “Timolol related compound D”, and “Total degradation products for Timolol Maleate” are different from what has been approved by the agency. We recommend revising the acceptance criteria to be consistent with what has been approved by the agency. We also recommend a combined acceptance criteria for “Total degradation products” for Brimonidine Tartrate and Timolol Maleate alternatively.
   2. We note that the suitability requirement for resolution for the test for “Organic Impurities, Brimonidine Tartrate” is NLT 1.1 between timolol maleate ester (free base of timolol related compound E) and brimonidine related compound A, which may not be sufficient to ensure adequate resolution of these two peaks. We recommend revising the suitability requirement acceptance criterion to NLT 1.5 as per USP practice observed in other monographs. We recommend that USP should contact the FDA approved applicants to obtain relevant information.

Call for Data: Doxepin Tablets (REF: 03-26-002-Z)
USP published a revision proposal for Doxepin Tablets in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a new monograph for this drug product.
USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

1. In the IMPURITIES section, we note that the acceptance criteria for “Total degradation products” are different from what has been approved by the agency. We recommend revising the acceptance criteria to be consistent with what has been approved by the agency. We recommend that USP should contact the FDA approved applicants to obtain relevant information.

Call for Data: Esomeprazole Sodium (REF: 03-26-010-H)
USP published a revision proposal for Esomeprazole Sodium in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a new monograph for this drug substance.
USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

1. Regarding the “Assay” test: Although the less specific titration method for assay may be acceptable, given the two HPLC purity tests, a new monograph can be an opportunity to assure that the most modern analytical techniques are used, making it less likely to require modernization in the near future. Therefore, we continue to recommend the inclusion of a HPLC based assay method as it would be an appropriate analytical technique for this monograph.
   Call for Data: Gadodiamide (REF: 03-26-007-H)
   USP published a revision proposal for Gadodiamide in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a major revision to the monograph for this drug substance.
   USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

2. Under the test for “Organic Impurities,” we note there is a limit of 0.2% for ‘Any unspecified impurity.’ However, this limit is not appropriate for a public standard as it exceeds the identification threshold (IT) per ICH Q3A guidelines. Therefore, we recommend tightening the limit to be consistent with ICH Q3A IT.
   Call for Data:  Glycopyrrolate (REF: 03-26-006-H)
   USP published a revision proposal for Glycopyrrolate in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a major revision to the monograph for this drug substance.
   USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

3. In the newly proposed drug substance structures under the Chemical Information section, the stereochemical definition (threo/erythro) has been removed at the benzylic stereocenter resulting in the loss of R or S configuration. Therefore, we recommend retaining the alpha and beta orientations of the cyclopentyl ring at the benzylic carbon as in the currently official monograph.

4. Under the test for “Organic Impurities, Procedure 1”:

   1. For Glycopyrrolate related compound A single limit of 0.15% (as in the currently official monograph) or the proposed limit of 0.016% for RC A is not appropriate for a public standard. A limit of 0.15% is too wide for products with higher MDDs and 0.016% is too restrictive for other products with lower MDDs. Therefore, we continue to recommend a flexible approach to allow different limits based on different products.
   2. Additionally, the statement in briefing section that “The acceptance criterion for glycopyrrolate related compound A is tightened from 0.15% (w/w) to 0.016% (w/w) to align with International Council for Harmonization (ICH) M7 guidelines since this impurity is a potential mutagenic impurity” will not be included in the monograph when the proposed revisions become official. Therefore, we recommend adding a footnote stating that this impurity possesses a structural alert for mutagenicity and FDA may ask for different limits based on ICH M7 guidelines.

Call for Data: Hexaminolevulinate Hydrochloride (REF: 03-26-009-H)
USP published a revision proposal for Hexaminolevulinate Hydrochloride in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a new monograph for this drug substance.
USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

1. Under the test for “Organic Impurities” the limit for ‘Total impurities’ is wider than what has been approved by the agency. We recommend that USP contact the FDA approved applicants to obtain relevant information and tighten the limit to be consistent with what has been approved by the agency.
2. The prescribing information for the Hexaminolevulinate Hydrochloride drug product in DailyMed states that it is a powder that needs to be reconstituted, indicating that it should be sterile. But the monograph has only the Bacterial Endotoxin test. Therefore, we recommend that USP contact the FDA approved applicants to obtain relevant information and include the microbial tests in the monograph.

Call for Data: Ketoconazole Cream (REF: 03-26-003-Z)
USP published a revision proposal for Ketoconazole Cream in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a new monograph for this drug product.
USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

1. In the IMPURITIES section,
   1. We note that the acceptance criteria for “Total degradation products” are different from what has been approved by the agency. We recommend revising the acceptance criteria to be consistent with what has been approved by the agency.
   2. We recommend including an acceptance criterion for “Relative standard deviation” in the suitability requirements.
2. In the SPECIFIC TESTS section, we note that the acceptance criteria for “pH 〈791〉” are different from what has been approved by the agency. We recommend revising the acceptance criteria to be consistent with what has been approved by the agency. We recommend that USP should contact the FDA approved applicants to obtain relevant information.

Call for Data: Levothyroxine Sodium for Injection (REF: 03-26-004-Z)
USP published a revision proposal for Levothyroxine Sodium for Injection in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a new monograph for this drug product.
USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

1. Based on information available to FDA, we recommend that USP work with the marketed manufacturers to ensure that the marketed products will be able to meet the requirements in the proposed monograph in order to avoid a drug shortage.
2. In the IMPURITIES section, we note that the acceptance criteria for “N-formyl levothyroxine” are different from what has been approved by the agency. We recommend revising the acceptance criteria to be consistent with what has been approved by the agency.
3. In the SPECIFIC TESTS section, we note that the acceptance criteria for “pH 〈791〉” are different from what has been approved by the agency. We recommend revising the acceptance criteria to be consistent with what has been approved by the agency. We recommend that USP should contact the FDA approved applicants to obtain relevant information.

Call for Data: Penciclovir (REF: 03-26-008-H)
USP published a revision proposal for Penciclovir in Pharmacopeial Forum (PF), Vol. 52, No. 1, which introduced a introduced a new monograph for this drug substance.
USP is interested in working with FDA approved applicants in order to help address the following comments provided by FDA:

1. The acceptance criterion in the test for “Water Determination” is different from what has been approved by the agency. We recommend that USP contact the FDA approved applicants to obtain relevant information and revise the limit to be consistent with what has been approved by the agency.