COMMENTARY - US Pharmacopeial Convention

General Chapters
General Chapter/Section(s): Injections/Ingredients
Expert Committee(s): Excipient Monographs 2/General Chapters–Parenteral
Products Industrial
No. of Commenters: 3
Comment Summary #1: The commenters suggested three changes to Aqueous
vehicles: 1) use the Coulometric Karl Fisher titration method, which is more suitable for
determination of low water contents, 2) allow the use of commercial Karl Fisher
Reagents, and 3) remove chloroform due to its toxicity.
Response: Comments incorporated. The Expert Committee revised the Water method
from Method Ia to Method Ic (Coulometric Karl Fisher titration) and deleted a proposed
solvent.
Comment Summary #2: In the Limit of copper, iron, lead, and nickel test, a commenter
indicated that metal catalysts are not used in unhydrogenated oils manufacturing and
therefore nickel is not likely to be an impurity.
Response: Comment incorporated. The Expert Committee clarified the impurities
requirements by adding a Note to the Limit of copper, iron, lead and nickel test.
General Chapter/Section(s): Test for 1,6-Anhydro Derivative for Enoxaparin
Sodium/Multiple Sections
Expert Committee(s): Biologics and Biotechnology–Blood and Blood Products
No. of Commenters: 3
Comment Summary #1: The commenters indicated that the equation provided to
calculate the mole percent of components containing a 1,6-anhydro structure is not
correct.
Response: Correction incorporated.
Comment Summary #2: The commenter indicated the assumption is not accurate that
all species observed in the chromatogram have an equivalent response factor.
Response: Comment not incorporated because the assumption is based on an
equivalent molar response factor.
Comment Summary #3: The commenters suggested adding a chromatogram with
annotation.
Response: Comment incorporated. A reference chromatogram will be provided with the
instructions for use of the relevant USP Reference Standards.
Comment Summary #4: The commenters suggested adding the following additional
Reference Standards: 1) a control Enoxaparin Reference Standard that can be digested
and chromatographed as part of system suitability, and 2) a disaccharide solution
containing the ΔIS 1,6-anhydro and the ΔIS-IS 1,6-anhydro compounds.
Response: Comment incorporated to include the control Enoxaparin Sodium Reference
Standard (RS). The disaccharide compounds are commercially available as reagents.
Comment Summary #5: The commenter suggested that the depolymerization
suitability specification was not met.
Response: Comment not incorporated because submitted results were obtained on the
formulated drug product. The results clearly indicate an incomplete depolymerization. It
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