BRIEFING

 Acyclovir Capsules. This proposal is based on the version of the monograph official prior to 2013. It is proposed to revise the monograph with the following changes:

1. Add Identification B, which is based on the UV spectra agreement as obtained in the Assay. Accordingly, revise the Detector in the Assay to support the proposed Identification B.

2. In the Assay:

   • Delete System suitability solution B because it is not needed to establish System suitability criteria. Accordingly, System suitability solution A is renamed as System suitability solution.

   • Replace guanine as a reagent with USP Guanine RS in the System suitability solution.

   • Replace the Column, which is not commercially available, with a commercially available column of the same L1 packing and column length but different column diameter.

   • Revise the flow rate from "1.5 mL/min" to "1.8 mL/min" to align with the Column diameter change.

   • Add the Tailing factor in the Suitability requirements section.

   • Revise the Suitability requirements for the Relative standard deviation to be consistent with the expectations of a modern chromatographic system.

3. In the Dissolution test:

   • Clarify the Standard solution preparation.

   • Add the calculation to align with current practices.

4. Remove the phrase "for Content Uniformity" from the Uniformity of Dosage Units test to align with the current USP style.

5. Revise the Impurities section to include a new Organic Impurities test for the analysis of any unspecified degradation product and total degradation products, and rename the old Procedure as the Limit of Guanine test. The new Organic Impurities test is based on an HPLC procedure validated with the Zorbax SB C8 brand of column with L7 packing. The typical retention time for acyclovir is about 20 min.

6. In the test for Limit of Guanine:

   • Add the Standard solution to support the proposed Relative standard deviation requirement and add the System suitability requirement for Relative standard deviation.

   • Clarify the calculation in the Analysis section to indicate it is for the analysis of guanine only.

7. Update the Packaging and Storage section to be consistent with the approved drug product inserts.

8. Update the USP Reference Standards section to include USP Guanine RS to support the Assay and Organic Impurities test.

 Additionally, minor editorial changes have been made to update the monograph to current USP style.

 (SM1: S. Parepalli)

 Case ID: SUB-831