Docket Management
Docket: 00D-1418 - Q7a ICH Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Comment Number: EC -13

Accepted - Volume 1

Comment Record
Commentor Mr. Jody Voight Date/Time 2000-10-02 16:53:00
Organization Abbott Laboratories
Category Company

Recommended Changes / Reasons
Lines: 79-79
Section: 1.3
provide a glossary definition for the term "biotech"
Recommended Change Type: Add new definition, section, or item. The term "Biotech" is used throughout the document and in the introduction in regard to requirements. The term is open to interpretation because it is not defined within the document.
Lines: 99-101
Section: 2.14
Use consistent requirement in reference to deviations such as "investigated and justified."
Recommended Change Type: General Comments The treatment of deviations is not consistent within the document.
Lines: 130-130
Section: 2.22
Use consistent requirement in reference to deviations such as "investigated and justified."
Recommended Change Type: General Comments The treatment of deviations is not consistent within the document.
Lines: 157-158
Section: 2.3
Use consistent requirement in reference to deviations such as "investigated and justified."
Recommended Change Type: General Comments The treatment of deviations is not consistent within the document
Lines: 742-743
Section: 8.15
Use consistent requirement in reference to deviations such as "investigated and justified."
Recommended Change Type: General Comments The treatment of deviations is not consistent within the document.
Lines: 950-952
Section: 11.15
Use consistent requirement in reference to deviations such as "investigated and justified."
Recommended Change Type: General Comments The treatment of deviations is not consistent within the document.
Lines: 438-443
Section: 5.47
All changes to the computerized system should be made according to a change procedure. and Critical changes should be formally authorized, documented and tested. Records should be kept of all changes including modifications and enhancements made to the hardware, software and any other critical component of the system to demonstrate that the final system is maintained in a validated state.
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The current wording will not allow for minor changes without formal authorization and testing. This level of change procedure may not be appropriate for minor changes.
Lines: 467-468
Section: 6.14
Remove the statement "in order performed."
Recommended Change Type: Revise, change, add or delete words or portions of sentences. Statement "when entries need to be made in records…directly after performing the activities (in the order performed)…" "in the order performed" and can be removed. The statement is redundant.
Lines: 639-640
Section: 7.12
The term "specification" should be changed to "acceptance criteria".
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The glossary definition of "specification" would imply that suppliers are required to test material per the manufacturers methodology. In some instances equipment or expertise may not be available to smaller suppliers to perform testing.
Lines: 730-731
Section: 8.12
Change word "supervised" to witnessed or verified.
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The statement "operations should be supervised..." implies that a person of higher level must verify critical activities.
Lines: 771-771
Section: 8.32
Change statement to "critical in-process controls (and critical process monitoring)... should be stated in writing and approved by the quality unit(s)."
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The statement is not clear as written and may be interpreted that both critical in-process controls and all process monitoring must be stated in writing and approved by the quality unit(s).
Lines: 967-968
Section: 11.18
Change statement in 11.18 to "This standard may be prepared by independent synthesis or from existing production material of acceptable purity.
Recommended Change Type: Revise, change, add or delete words or portions of sentences. Companies should determine how a reference standard is prepared. "This standard may be prepared by independent synthesis or by purification of existing production material" may be too restrictive for production material which is of acceptable purity.
Lines: 984-985
Section: 11.21
There should be an option for including minor impurities in a "total unidentified impurities" specification (with a "largest single impurity" range specified), which is recognized in the major compendia
Recommended Change Type: Revise, change, add or delete words or portions of sentences. "the range of each impurity observed" is vague for unidentified impurities for "classical fermentation" processes. Without appropriate standards, unidentified impurities may not be quantified since a response factor (HPLC) cannot be established.
Lines: 989-992
Section: 11.22
This should be modified to require an impurity profile (qualitative and quantitative) comparison against previously produced material (from the regulatory submission and/or validation documents) whenever a change is made to a critical process step.
Recommended Change Type: Revise, change, add or delete words or portions of sentences. Comparison should be made against both the regulatory submission and validation documents. This comparison should be done whenever a change is made to what is considered a critical process step.
Lines: 1268-1269
Section: 13.15
Change to After major (or significant) changes that may impact the quality of the API, there should be an evaluation of the first batches produced or tested under the change.
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The statement as written does not allow for minor changes which may not have an impact on product quality to be implemented without evaluation of the next batches.
Lines: 1292-1294
Section: 14.21
Modify 14.21 to state "Continuation of a process step after an in-process control test shows the step to be incomplete is considered to be part of the normal process. This is not considered to be reprocessing.
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The example is very specific to chemical manufacturing, with reference to fermentation and biotech manufacturing within the document the example provided for reprocessing and the glossary definition should be more universal in nature.
Lines: 1819-1820
Section: 20
Reprocessing-…continuation of a chemical reaction process step after an in-process control test...
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The example is very specific to chemical manufacturing, with reference to fermentation and biotech manufacturing within the document the example provided for reprocessing and the glossary definition should be more universal in nature.
Lines: 1539-1544
Section: 18.33
Reword "Critical operating parameters..." to "Operating parameters that have been determined to be critical to the quality of the API..."
Recommended Change Type: Revise, change, add or delete words or portions of sentences. The use of the word critical, as defined in the glossary, would imply specifications. Unqualified, the statement implies that there are critical parameters in every case. As written, the use of the word critical suggests that every fermenatation process has a critical parameter that would require specifications in addtiion to basic control. In some instances, classical fermentation processes are essentially a "go/no-go" event where only the production of the API, or API starting material, is important to the process.
Lines: 1682-1682
Section: 20
Include definition of clinical material in glossary. "Clinical APIs - APIs used in drug products intended for clinical trials in human use only."
Recommended Change Type: Add new definition, section, or item. The document makes reference to clinical material however does not difine this term in the glossary.



EC -13