The quality control deparment is response of test of samples. And QA deparment is response of checking all of the staff to follow SOPs(standard of operation).
1. HGH samples should be tested according to following items
|Items of Test||Standard|
|Characters||White lyophilized powder|
|A.||IEF||CORRESPONDS TO THE REFERENCE|
|B.||HPLC/RP||CORRESPONDS TO THE REFERENCE|
|C.||PEPTIDE MAPPING||CORRESPONDS TO THE REFERENCE|
|D.||HPLC/SEC||CORRESPONDS TO THE REFERENCE|
|RELATED PROTEINS (HPLC/RP)||≤ 13.0%|
OF HIGHER MOLECULAR MASS
|ISOFORM DISTRIBUTION||CORRESPONDS TO THE REFERENCE|
|BACTERIAL ENDOTOXINS||＜ 5.0 IU/mg hGH|
|HOST-CELL-DRIVED PROTEINS||≤ 30 ng/mg hGH|
|HOST-CELL & VECTOR-DERIVED DNA||≤ 10 ng/dose hGH|
|TEST FOR STERILITY||conformed|
|ASSAY (HPLC/SEC)||89.0% - 105.0 % the amount of Somatropin stated on the label|
|Purity (HPLC)||≥ 95%|
2. Endotoxin Control
Endotoxin contamination of an injectable product can occur as a result of poor CGMP controls.
Certain patient populations (e.g., neonates), those receiving other injections concomitantly, or
those administered a parenteral in atypically large volumes or doses can be at greater risk for
pyrogenic reaction than anticipated by the established limits based on body weight of a normal
healthy adult (Ref. 6, 7). Such clinical concerns reinforce the importance of exercising
appropriate CGMP controls to prevent generation of endotoxins. Drug product components,
containers, closures, storage time limitations, and manufacturing equipment are among the areas
to address in establishing endotoxin control.
Adequate cleaning, drying, and storage of equipment will control bioburden and prevent
contribution of endotoxin load. Equipment should be designed to be easily assembled and
disassembled, cleaned, sanitized, and/or sterilized. If adequate procedures are not employed,
endotoxins can be contributed by both upstream and downstream processing equipment.
Sterilizing-grade filters and moist heat sterilization have not been shown to be effective in
removing endotoxin. Endotoxin on equipment surfaces can be inactivated by high-temperature
dry heat, or removed from equipment surfaces by cleaning procedures. Some clean-in-place
procedures employ initial rinses with appropriate high purity water and/or a cleaning agent (e.g.,
acid, base, surfactant), followed by final rinses with heated WFI. Equipment should be dried
following cleaning, unless the equipment proceeds immediately to the sterilization step.
3. Microbiological Media and Identification
Characterization of recovered microorganisms provides vital information for the environmental
monitoring program. Environmental isolates often correlate with the contaminants found in a
media fill or product sterility testing failure, and the overall environmental picture provides
valuable information for an investigation. Monitoring critical and immediately surrounding
clean areas as well as personnel should include routine identification of microorganisms to the
species (or, where appropriate, genus) level. In some cases, environmental trending data have
revealed migration of microorganisms into the aseptic processing room from either uncontrolled
or lesser controlled areas. Establishing an adequate program for differentiating microorganisms
in the lesser-controlled environments, such as Class 100,000 (ISO 8), can often be instrumental
in detecting such trends. At minimum, the program should require species (or, where
appropriate, genus) identification of microorganisms in these ancillary environments at frequent
intervals to establish a valid, current database of contaminants present in the facility during
processing (and to demonstrate that cleaning and sanitization procedures continue to be
Genotypic methods have been shown to be more accurate and precise than traditional
biochemical and phenotypic techniques. These methods are especially valuable for
investigations into failures (e.g., sterility test; media fill contamination). However, appropriate
biochemical and phenotypic methods can be used for the routine identification of isolates.
The goal of microbiological monitoring is to reproducibly detect microorganisms for purposes of
monitoring the state of environmental control. Consistent methods will yield a database that
allows for sound data comparisons and interpretations. The microbiological culture media used
in environmental monitoring should be validated as capable of detecting fungi (i.e., yeasts and
molds) as well as bacteria and incubated at appropriate conditions of time and temperature.
Total aerobic bacterial count can be obtained by incubating at 30 to 35 o C for 48 to 72 hours.
Total combined yeast and mold count can generally be obtained by incubating at 20 to 25 o C for 5
to 7 days.
Incoming lots of environmental monitoring media should be tested for their ability to reliably
recover microorganisms. Growth promotion testing should be performed on all lots of prepared
media. Where appropriate, inactivating agents should be used to prevent inhibition of growth by
cleanroom disinfectants or product residuals (e.g., antibiotics).
3. TIME LIMITATIONS
When appropriate, time limits must be established for each phase of aseptic processing.
Time limits should include, for example, the period between the start of bulk
product compounding and its sterilization, filtration processes, product exposure while on the
processing line, and storage of sterilized equipment, containers and closures. The time limits
established for the various production phases should be supported by data. Bioburden and
endotoxin load should be assessed when establishing time limits for stages such as the
formulation processing stage.
The total time for product filtration should be limited to an established maximum to prevent
microorganisms from penetrating the filter. Such a time limit should also prevent a significant
increase in upstream bioburden and endotoxin load. Because they can provide a substrate for
microbial attachment, maximum use times for those filters used upstream for solution
clarification or particle removal should also be established and justified.