Docket Management
Docket: 00D-1418 - Q7a ICH Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Comment Number: ECT-3

Accepted - Volume 1

Comment Record
Commentor Mr. John DeFoe Date/Time 2000-10-20 00:00:00
Organization Pfizer Inc
Category API/Dosage Manufacturers

Recommended Changes / Reasons
Lines: 1-1
Section: 1
The FDA should be commended for their participation in the multinational industry-regulatory collaboration that produced this guidance document. It is our opinion that the ICH document which resulted from the input and discussion among regulatory agencies and industry associations in the three ICH areas as well as from the additional participants from non-ICH countries is superior to the various documents on this topic that were published by individual groups in the past. We believe that a process of open exchange between industry and regulators is invaluable in developing documents useful to both, and encourage FDA to continue to solicit collaboration in the development of future guidance documents.
Recommended Change Type: General Comments
Lines: 2322-2327
Section: 20
Throughout the document, the frequent and inconsistent use of the word "specifications" should be replaced by the word "specification".
Recommended Change Type: General Comments As defined in the glossary, the term "specification" means the complete set of tests, procedures, and acceptance criteria. The use of the term in the plural form in many, although not all, places in the document implies that there may or should be more than a single specification for a material.
Lines: 309-309
Section: 4.10
replace "specifications" with "acceptance criteria"
Recommended Change Type: General Comments This change would be consistent with the definition of specification in the glossary of this document and with the definitions included in ICH Q6A.
Lines: 264-265
Section: 3.12
Delete sentence, "The practical effectiveness of the training should be periodically assessed."
Recommended Change Type: General Comments The requirement and the means of fulfilling it are unclear.
Lines: 349-349
Section: 4.20
Change to read, "All product contact utilities...."
Recommended Change Type: General Comments We believe this is the intent of this section, however, it should be clearly stated to avoid any misunderstanding. Non-product contact utilities such as air used for instuments or steam used to heat reactor jackets generally do not have limits nor are they monitored as implied in this section.
Lines: 378-379
Section: 4.31
Delete "...that have been documented as at least equivalent to World Health Organization (WHO) guidelines."
Recommended Change Type: General Comments The required documentation of equivalency between different national and WHO standards is unclear as to the basis for determining equivalency or who would determine it. Moreover, it is unnecessary since the previous section (4.30) requires process water to be demonstrated as suitable for use in the manufacture of APIs, and the following section (4.32) requires tighter specification if potable water standards are insufficient to assure API quality. Consequently, the need to show equivalency between national and WHO potable water standards is a difficult and unnecessary burden without improving the quality of the API.
Lines: 960-961
Section: 8.21
delete section
Recommended Change Type: General Comments The requirements of this section are redundant to those of section 7.42.
Lines: 999-999
Section: 11.50/8.40
correct section number to 8.40
Recommended Change Type: General Comments
Lines: 1025-1025
Section: 8.45
change "...bulk density and tap density" to "...bulk density or tap density"
Recommended Change Type: General Comments Each item is a separate example.
Lines: 1031-1032
Section: 8.47
The term "manufacturing date" should be defined or described.
Recommended Change Type: General Comments
Lines: 1040-1040
Section: 8.50
Change "...and incomplete discharge of ..." to "...or incomplete discharge of..."
Recommended Change Type: General Comments Each item is a separate example.
Lines: 1227-1228
Section: 11.18
Change "...or by further purification of existing production material." to "...or from existing production material following further purification if appropriate."
Recommended Change Type: General Comments Production material without further purification may be adequate.
Lines: 1253-1256
Section: 11.22
This section should be deleted
Recommended Change Type: General Comments This requirement is unnecssary. Section 11.20 requires testing each batch for conformance to specification. For impurities included in the specification, this is adequate. Since section 11.14 requires that "appropriate specifications(sic) should be established for APIs in accordance with accepted standards and consistent with the manufacturing process. The specifications(sic) should include a control of the impurities...", any impurities not included in the specification are not necessary to be monitored or controlled. Moreover, it is unclear what if any actions would be required if impurities not included in the specification increased or decreased.
Lines: 1276-1277
Section: 11.42
Change " in accordance with compendial or customer requirements..." to "in accordance with the specification..."
Recommended Change Type: General Comments The certificate of analysis should reflect the specification.
Lines: 1460-1460
Section: 12.44
Change item (4) "impurity profiles" to "impurity acceptance criteria"
Recommended Change Type: General Comments This would be consistent with other portions of this document, ICH Q6A, and earlier recommendations for changes.
Lines: 1727-1727
Section: 16.10
Change to read, "All contract manufacturers (including laboratories) involved in activities within the scope of this guidance..."
Recommended Change Type: General Comments While we understand this to be the intent of the section, we believe it should be explicitedly stated.
Lines: 2199-2199
Section: 20
Correct citation to " See Active Pharmaceutical Ingredient"
Recommended Change Type: General Comments
Lines: 2215-2215
Section: 20
Change "specifications" to "specification"
Recommended Change Type: General Comments For consistency with definition of specification
Lines: 2287-2288
Section: 20
Change "...or by further purification of existing production material." to "...or from existing production material, following further purification if appropriate."
Recommended Change Type: General Comments Further purification may not be necessary.



ECT-3