Docket Management
Docket: 00D-1418 - Q7a ICH Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Comment Number: ECT-2

Accepted - Volume 1

Comment Record
Commentor Mr. Edmund Fry Date/Time 2000-10-20 00:00:00
Organization PDA
Category Association

Recommended Changes / Reasons
Lines: 74-74
Section: 1.3
Revise the beginning of the sentence on line 74 to read, "Within the API process itself, physical processing such as granulation..."
Recommended Change Type: General Comments Clarification.
Lines: 95-95
Section: 2.12
Delete "all" from the beginning of the sentence.
Recommended Change Type: General Comments Statement is too broad as currently written.
Lines: 97-98
Section: 2.13
Revise sentence to read, "Quality related activities should be recorded when they are performed."
Recommended Change Type: General Comments Statement is too broad as currently written.
Lines: 99-99
Section: 2.14
Delete the word "any" from the beginning of section 2.14.
Recommended Change Type: General Comments Statement is too broad as currently written.
Lines: 112-115
Section: 2.17
Delete the end of the sentence in Section 2.17 beginning with, "unless there are appropriate systems in place to allow for such..."
Recommended Change Type: General Comments It is inappropriate to use unreleased materials.
Lines: 119-119
Section: 2.20
Delete the term "all" from "...all quality-related matters" to read "...quality-related matters."
Recommended Change Type: General Comments As presently stated, the directive is too broad.
Lines: 120-120
Section: 2.21
Delete the term "all" from "...all appropriate quality related documents."
Recommended Change Type: General Comments As presently stated, the directive is too broad.
Lines: 132-132
Section: 2.22
Omit the term "potentially" from item number 6 in section 2.22.
Recommended Change Type: General Comments The term "potentially" cannot be defined. Subject to uncertain interpretation.
Lines: 136-136
Section: 2.22
Omit the term "potentially" from item number 9 in section 2.22.
Recommended Change Type: General Comments The term “potentially” cannot be defined. Subject to uncertain interpretation.
Lines: 137-137
Section: 2.22
Revise "...validation protocols and reports" to read "validation documents" in item number 10 in section 2.22.
Recommended Change Type: General Comments Clarification.
Lines: 203-204
Section: 3.12
Delete the last sentence in section 3.12 that reads, "The practical effectiveness of the training should be periodically assessed."
Recommended Change Type: General Comments This statement goes beyond current GMPs.
Lines: 207-207
Section: 3.21
Delete the word "clean" from the first sentence in secton 3.21.
Recommended Change Type: General Comments Suitable clothing for manufacturing should be "clean," "neat," and possess all other necessary properties.
Lines: 288-288
Section: 4.30
Delete the phrase "demonstrated to be" in section 4.30.
Recommended Change Type: General Comments The pharmacopoeias specify the quality of water which is used for pharmaceutical purposes. It is not necessary to verify and demonstrate the appropriateness of pharmacopoeial specifications.
Lines: 300-300
Section: 4.33
Revise section 4.33 to read, "...with appropriate alert and action limits."
Recommended Change Type: General Comments Clarification.
Lines: 309-309
Section: 4.40
Revise the sentence to read, "...production of highly sensitizing materials, such as penicillins or cephalosporins."
Recommended Change Type: General Comments Sensitizing materials like penicillins and cepahlosporins should be manufactured in dedicated production areas. However the word "type" may cause a misinterpretation. There are some kinds of beta-lactam materials having different sensitizing natures. Generally, penicillins and cephalosporins are recognized as highly sensitizing materials, the former more than the latter, so dedicated facilities are typically used. Then how should other kinds of beta-lactams, like carbapenems, be considered? Considering them as another "type" only based on the chemical skeleton, they should be handled in a different production area from cephalosporins. However, there are certain carbapenems that are almost equivalent to cephalosprins in antigenicity against certain animals on preclinical investigation, and in sensitivity and anaphylaxis in human beings on clinical investigation. In such cases we believe they can be manufactured in the same production area. There are undoubtedly other examples like that. Therefore, the definition of "type" should be clarified to mean categorized based on the degrees of antigenicity, sensitivity, anaphylaxis, etc., not only based on the structure of the materials.
Lines: 335-335
Section: 4.71
Add "where appropriate" to the end of the sentence in section 4.71.
Recommended Change Type: General Comments To make the section consistent with sections 5.10 and 5.22.
Lines: 336-336
Section: 4.72
Delete "When necessary" from the beginning of the sentence in section 4.72. The section should read, "Written procedures should also..."
Recommended Change Type: General Comments To comply with current practice.
Lines: 366-366
Section: 5.20
Delete the term "preventative" from the sentence in section 5.20.
Recommended Change Type: General Comments “Preventive maintenance” is only one type of maintenance that must be performed. “Preventive action” is an important concept, but has wide meaning, and specified in ISO 9000/2000 8.5.3(“Preventive action”). In this case, “maintenance” is enough. If GMP includes “Preventive action” as required in ISO 9000/2000, preventive action should be specified in other parts.
Lines: 385-385
Section: 5.21
Revise the last bullet point in section 5.21 to read, "Establishing the maximum time that may elapse between the completion of processing and equipment cleaning, and before the re-use when appropriate."
Recommended Change Type: General Comments It may be appropriate in certain situations to establish a time limit for the use of cleaned equipment, i.e., how long the cleaned equipment may be held before re-use.
Lines: 455-455
Section: 6.11
Delete "with maintenance of revision histories" from the ending of the sentence is section 6.11.
Recommended Change Type: General Comments This requirement goes beyond current GMPs.
Lines: 631-631
Section: 6.73
Add "for further processing" to the end of the sentence is section 6.73.
Recommended Change Type: General Comments Clarification.
Lines: 656-660
Section: 7.22
Delete the second sentence in section 7.22 and the three bullet points following.
Recommended Change Type: General Comments A supplier audit may not be able to address the concern of contamination from the carrier’s equipment. An audit of the carrier’s facilities and procedures for tank cleaning would be more appropriate. This is a guidance document, not a “how-to” manual.
Lines: 726-726
Section: 8.11
Revise the first bullet point in section 8.11 to read, "Material name and/or item code."
Recommended Change Type: General Comments In some cases, material is handled by item code all throughout the firm.
Lines: 809-809
Section: 8.45
Replace the term "critical attributes" with "physical attributes" in the second sentence is section 8.45.
Recommended Change Type: General Comments The physical attributes may or may not be critical.
Lines: 920-921
Section: 10.23
Revise section 10.23 to read, "The API shipper should ensure that the contract acceptor for transportation of the API follows the appropriate transport and storage conditions."
Recommended Change Type: General Comments The API manufacturer may not have title to the product during shipment. The transporter simply needs to follow transport conditions.
Lines: 954-954
Section: 11.16
Revise the first sentence in section 11.16 to read, "...according to a predetermined/written procedure."
Recommended Change Type: General Comments Self explanatory.
Lines: 1176-1179
Section: 12.52
Revise the second sentence in section 12.52 to read, "The impurity profile should be substantially the same or better than historic data."
Recommended Change Type: General Comments The term “comparable” requires definition if it is to be used. Further, historic data clearly includes pivotal clinical and toxicological data.
Lines: 1289-1291
Section: 14.20
Revise the last sentence in section 14.20 to read, "However, if more than infrequent reprocessing is required, the reprocessing should be included as part of the standard manufacturing process."
Recommended Change Type: General Comments This statement must be consistent with the intent of Sec 12.40.
Lines: 1329-1329
Section: 14.43
Add "and validated" to the end of the sentence in section 14.43.
Recommended Change Type: General Comments The use of recovered materials should be validated.
Lines: 1619-1619
Section: 19.22
Revise the ending of the sentence in section 19.22 to read, "...other areas, provided that the quality unit reviews all of the data and provides the disposition."
Recommended Change Type: General Comments The wording of the previous draft (s. 18.21) is preferred.
Lines: 488-488
Section: 6.18
Delete the term "authenticated" in section 6.18.
Recommended Change Type: General Comments The term "authenticated" should be deleted or defined in the glossary.



ECT-2