Docket Management
Docket: 00D-1418 - Q7a ICH Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Comment Number: ECT-4

Accepted - Volume 1

Comment Record
Commentor Dr. Anders Vinther Date/Time 2000-10-20 00:00:00
Organization Novo Nordisk
Category API/Dosage Manufacturers

Recommended Changes / Reasons
Lines: 37-37
Section: 1.3
Change sentence to read "...covers intermediates and APIs that are manufactured by..."
Recommended Change Type: General Comments By adding "intermediates and" it is specified that intermediates are covered by the guidance.
Lines: 79-79
Section: 1.3
"Classical" fermentation should be defined
Recommended Change Type: General Comments Will clarify the document
Lines: 79-79
Section: 1.3
Biotech/fermentation cell culture. We suggest "Establishment of master cell bank and working cell bank" to be covered by the GMPs.
Recommended Change Type: General Comments In practice establishment of master cell bank and working cell bank is being inspected as being part of the GMPs. We find that acceptable as this part of the process is crucial to later on-going manufacturing
Lines: 111-115
Section: 2.17
Delete the rest of the sentence after "...completion of evaluation by the quality unit(s)"
Recommended Change Type: General Comments Release under quarantine is not allowed according to 21 CFR 211.84 and The Rules Governing Medicinal Products in the European Union, Volume 4, Section 5.31. The same recommendation applies to section 10.20, lines 912-915.
Lines: 188-188
Section: 2.50
Change sentence to read "- A conclusion of the Product Quality Review including an evaluation of the adequacy of corrective actions"
Recommended Change Type: General Comments The Product Quality Review should include a conclusion. Part of that is an evaluation of the adequacy of corrective actions based among other things on some of the bullet points mentioned in lines 181-187. Therefore the sentence is partly an integrated part of the above.
Lines: 203-204
Section: 3.12
Change the sentence to read "Training should be periodically assessed"
Recommended Change Type: General Comments The assessment of training effectiveness goes beyond current GMP. On the other hand, we find that periodic assessment of training should be done. It should be up to the company to decide how. Training is indirectly assessed by various elements in the Product Quality Review (e.g. human errors as reason for deviations, etc.)
Lines: 257-261
Section: 4.15
Delete the sentences after the first sentence of the section.
Recommended Change Type: General Comments The sentences is an example on the use of "how to" rather than "what to"
Lines: 298-300
Section: 4.33
Add alert limit to sentence, so that it reads: "..., the treatment process should be validated and monitored with appropriate alert and/or action limits."
Recommended Change Type: General Comments It is common practice to use action as well as alert limits in API production
Lines: 370-385
Section: 5.21
Delete the sentences after the sentence that ends "...in a reproducible and effective manner".
Recommended Change Type: General Comments The sentences is an example on "how to" rather than "what to".
Lines: 599-599
Section: 6.60
Change the sentence to read "- A complete record of all raw data generated during each test,..."
Recommended Change Type: General Comments The word "generated" better describes the issue than "secured", which is not easy to understand in this context.
Lines: 743-743
Section: 8.15
Add a new sentence, that reads "Short-term predefined excursions outside alert or action limits do not necessarily lead to deviation investigations, but should be documented and explained, e.g. as part of the batch production record."
Recommended Change Type: General Comments For complex biotech processes numerous alert and/or action limits are typically defined during fermentation and down-stream processing. Short-term predefined excursions outside these limits may be known to have no practical effect on the quality of the product or processes and should only lead to notations in e.g. the batch production record. Example: pH is specified to be in the range 6.0 to 7.0 for 72 hours. An excursion to pH 5.9 for 10 minutes is observed. In case this is known to have no effect on the quality of the product, no deviation report should be issued.
Lines: 831-831
Section: 9.10
Before the first sentence add new sentence, that reads "Section 9 only applies to API's and intermediates that are being transported outside the company. Labelling requirements for API's and intermediates that are being transferred within the company or within the same production site should be defined and documented by the company."
Recommended Change Type: General Comments Even though the section does not apply to API's and intermediates that are being transferred within the same company it is important that company specific requirements are being defined. By adding the sentence it will clarify the document.
Lines: 912-915
Section: 10.20
Delete the sentence after the sentence that ends "...been released by the quality unit(s)".
Recommended Change Type: General Comments Release under quarantine is not allowed according to 21 CFR 211.84 and The Rules Governing Medicinal Products in the European Union, Volume 4, Section 5.31.
Lines: 1114-1116
Section: 12.30
We suggest the definition to read "Installation Qualification (IQ) is documented verification that the equipment or system as installed or modified, comply with the approved design of critical feautures"
Recommended Change Type: General Comments Focus should be on critical features of the equipment or system, not on manufacturer's recommendations. Also this is more in line with the ISPE Baseline Guide on Commisioning and Qualification, thus leading to further harmonisation.
Lines: 1212-1213
Section: 12.74
Change sentence to read "Validated analytical procedures having properties to detect..."
Recommended Change Type: General Comments ICH Q2A and ICH Q2B use the term "Analytical procedures" instead of analytical methods. "Sensitivity" has its own use and definition for analytical procedures.
Lines: 0-0
Section: 0.0
Change the wording "Analytical Methods" with "Analytical Procedures".
Recommended Change Type: General Comments ICH Q2A and ICH Q2B use the wording analytical procedures rather than analytical methods.
Lines: 1214-1214
Section: 12.74
Change the wording from "...suficciently sensitive to detect.." to "... sufficient to detect..."
Recommended Change Type: General Comments "Sensitivity" has its own use and definition for analytical procedures.
Lines: 32-32
Section: 1.3
Change sentence to read "...applies to the manufacture of intermediates and APIs for use..."
Recommended Change Type: General Comments Addition of "intermediates and" specifies that the guidance also covers intermediates.
Lines: 39-39
Section: 1.3.
Change sentence to read "Specific guidance for intermediates and APIs manufactured by cell..."
Recommended Change Type: General Comments By adding "intermediates and" it is specified that intermediates are covered by the guidance.
Lines: 1117-1119
Section: 12.30
Change definition to read "Operational Qualification (OQ) is documented verification that the equipment or system as installed or modified perform as intended throughout the approved operating range of critical functions".
Recommended Change Type: General Comments Focus should be on critical features of the equipment or system. Also this is more in line with the ISPE Baseline Guide on Commisioning and Qualification, thus leading to further harmonisation.
Lines: 1120-1123
Section: 12.30
Change definition to read "Performance Qualification (PQ) is documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on approved procedures and user requirements identified to be critical"
Recommended Change Type: General Comments Focus should be on critical features of the equipment or system. Also this is more in line with the ISPE Baseline Guide on Commisioning and Qualification, thus leading to further harmonisation.



ECT-4