【资料】COMMENTARY-USP 32/NF 27 First Supplement

General Chapters
General Chapter/Section(s): <191> Identification Tests–General/Multiple Sections
Expert Committee(s): General Chapters
No. of Commenters: 1
Comment Summary #1: For both the Acetate Identification test and the Ammonium Identification test, the commenter requested including an “equivalent or better”analytical method for species identification and the presentation of a better profile from safety, health and cost effectiveness standpoint. The commenter recommended either leaving the identification test “as is” or eliminating the odor testing portion of the existing test and soliciting input from stakeholders on an identification test that is more innocuous.
Response: Comments not incorporated. The USP General Notices allows
manufacturers to use alternative methods so it is not necessary to specify this in the chapter. With regard to the changes to the identification test, organoleptic tests are being removed from official text for safety reasons. The General Chapters Expert Committee is initiating a revision of all identification tests in General Chapter <191> to address safety concerns and clarify the procedures.
General Chapter/Section(s): <401> Fats and Fixed Oils/Multiple Sections
Expert Committee(s): Excipient General Chapters/Dietary Supplement-NonBotanicals
No. of Commenters: 3
Comment Summary #1: The commenter suggested revising the Saponification Value
section because the description of the calculation was incorrect. The corrected calculation formula reads: [56.11(VB - VT) N]/W.
Response: Comment incorporated.
Comment Summary #2: The commenter requested revising the Polyunsaturated Fatty
Acids Determination and Profile section to include other types of polyunsaturated fatty acids in addition to “EPA, DHA, and the other chain-desaturated and/or chain-elongated members of the omega-3 family.”
Response: Comment incorporated by changing section title from “Polyunsaturated Fatty Acids Determination and Profile” to “Omega-3 Fatty Acids Determination and Profile.”
Comment Summary #3: The commenter requested revising the Polyunsaturated Fatty
Acids Determination and Profile section to include “families of other fatty acids (i.e., the
omega-6, omega-9, or omega-7).”
Response: Comment not incorporated because no supporting data was provided. The Expert Committee is willing to consider future changes to the General Chapter upon receipt of supporting data.
Comment Summary #4: The commenter requested revising the Polyunsaturated Fatty
Acids Determination and Profile section changing analytical column from G-16 to a number of other “columns of choice due to their enhanced selectivity and separation characteristics.”
Response: Comment not incorporated because no supporting data was provided. The Expert Committee is willing to consider future changes to the General Chapter upon receipt of supporting data.

General Chapter/Section(s): <467> Residual Solvents/Pressurization Time
Expert Committee(s): General Chapters
No. of Commenters: 1
Comment Summary #1: The commenter requested two changes to the Pressurization
time section: 1) increase the syringe temperature range 5 to 10ºC higher than the
equilibration temperature and 2) add the phrase “if appropriate” because equilibration
temperatures are typically used for injectors with a transfer line. Pressurization time is
not applicable to syringe-based injectors.
Response: Comment incorporated.
General Chapter/Section(s): <1010> Analytical Data-Interpretation and Treatment/
Multiple Sections
Expert Committee(s): Statistics
No. of Commenters: 3
Comment Summary #1: The commenter indicated that in the Sampling Considerations
section, systematic random sampling is recommended as a sampling scheme that may
be preferred to simple random sampling in certain situations. While the stated reasons
are valid, there are analytical issues with variance estimation associated with data
collected via systematic sampling. Although the last sentence of the sub-section states
that the tests discussed in the remainder of the chapter assume that simple random
sampling was performed, the commenter recommend including an additional statement
recommending consultation with a statistician to identify the optimal sampling strategy.
Response: Comment incorporated.
Comment Summary #2: The commenter indicated that in Appendix C, the
recommended approach assesses the data first for a single outlier (correctly), then tests
the reduced dataset again, using the same approach, to ensure there are no other
outliers on the same side of the mean. The commenter viewed this as incorrect
because there are outlier tests designed for more than one outlier on the same side of
the mean. However, the commenter noted the warning in the conclusion and suggested
making the warning more prominent at the end or beginning of Appendix C.
Response: Comment incorporated. The following text was added under the Dixon-Type
Tests subsection: "Dixon provides for testing for two outliers simultaneously; however,
these procedures are beyond the scope of this Appendix. The stepwise procedure
discussed below is not an exact procedure for testing for the second outlier as the result
of the second test is conditional upon the first. Because the sample size is also reduced
in the second stage, the end result is a procedure that usually lacks the sensitivity of
Dixon's exact procedures.” The conclusion paragraph was replaced with the following
text: “Therefore, 95.7 is declared to be an outlier but 99.5 is not an outlier.”
Comment Summary #3: The commenter indicated that Appendix E, Sample Size
section, the formula for 2
L σ should be revised throughout the entire chapter from “RSD”
to “%RSD.”
Response: Comment incorporated.
Expert Committee-initiated Change #1: Under Appendix B, the Expert Committee
members proposed to revise the sentence from “Nevertheless, many statistical software
packages can easily handle unequal replication" to “Many statistical software packages
can easily handle unequal replication.”

General Chapter/Section(s): <1078> GMP for Bulk Pharmaceutical Excipients/Multiple
Sections
Expert Committee(s): Excipient General Chapters
No. of Commenters: 3
Comment Summary #1: The commenter proposed replacing “In these cases,
consultation and adaptation of detailed guidelines and compliance programs is
recommended as necessary for the excipient in question," with "In these cases, detailed
information pertaining to the intended use of excipient as provided by the end-user can
be useful in determining appropriate GMP."
Response: Comment incorporated.
Comment Summary #2: The commenter proposed amending Appendix I to add a
reference called Application of GMP Principles that provides a rationale for applying
appropriate GMP concepts at various stages of the manufacturing process.
Response: Comment not incorporated because the proposal reflects the current
approved marketed product.
Comment Summary #3: The commenter proposed replacing the statement
“Customers and, if necessary, regulatory authorities (for example, for Drug Master Files
[DMFs] or Certificates of Suitability to the European Pharmacopoeia [CEPs]) should be
notified of significant changes …” with "Customers should be notified and, where
applicable, excipient regulatory submissions (e.g. DMFs) should be amended to reflect
significant changes...."
Response: Comment incorporated.
Comment Summary #4: The commenter proposed replacing the statement "Water
used in the manufacture of excipients should be demonstrated to be of a quality suitable
for its intended use” with “Water used in the manufacture of excipients should be
demonstrated to be of appropriate quality in consideration of purity requirements and
intended use of the excipient.”
Response: Comment incorporated.
Comment Summary #5: The commenter proposed replacing the statement “Supplier
approval by the quality unit should require an evaluation of the supplier’s quality
management system, including adequate evidence that they can consistently agreed
requirements" with "Supplier approval by the quality unit should require an evaluation of
the supplier's Quality Management System, including adequate evidence that they can
consistently meet agreed upon specifications and maintain traceability."
Response: Comment incorporated.
Comment Summary #6: The commenter proposed adding the sentence “Excipient
manufacturers should also have adequate knowledge about the origin of any raw
materials derived from plant or animal matter.”
Response: Comment incorporated.
Comment Summary #7: The commenter proposed clarifying and expanding
Measurement, Analysis, and Improvement section, Expiry/Retest Periods subsection to
clearly describe the retest period and whether the stated retest period can be applied
once or multiple times.
Response: Comment not incorporated because the manufacturer provides information
on the expiry/retest period as appropriate with each excipient.
Comment Summary #8: The commenter proposed adding a statement regarding the
periodic auditing of raw material manufacturers to support the use of identification
testing only.
Response: Comment not incorporated because supplier auditing requirements are
defined and enforced by certification and regulatory bodies.
Comment Summary #9: The commenter proposed adding a statement to Appendix 2,
Documentation and Record Keeping subsection, suggesting an excipient manufacturer
can provide documentation of the supplier’s manufacturing sites.
Response: Comment not incorporated because the suggestion is more specific than
the regulatory requirements for who retains supplier manufacturing site documentation.
Comment Summary #10: The commenter proposed deleting statements or sections
that are redundant throughout the chapter.
Response: Comment not incorporated because the Expert Committee determined the
redundancy ensured clarity.
Comment Summary #11: The commenter proposed adding a statement on the use of
a second person to verify the operation or data in the control of documents section.
Response: Comment not incorporated because the record review requirements are
defined and enforced by certification and regulatory bodies.
Comment Summary #12: The commenter proposed adding a statement to strengthen
the notification process in the change control subsection under the Quality Management
System: Excipient Quality Systems.
Response: Comment not incorporated because the suggestion is more specific than
the regulatory requirements to ensure change control is appropriately communicated.
Comment Summary #13: The commenter proposed removing the phrases “whenever
feasible” and “otherwise verified prior to use” throughout the chapter.
Response: Comment not incorporated because the Expert Committee determined the
General Chapter wording is appropriate and allows for appropriate flexibility.

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COMMENTARY-USP 32/NF 27 First Supplement