发酵罐验证，相信大家对下面的文件比较熟悉

joke · 发表于 2013-8-21 22:28:20

FERMENTOR (BIOREACTOR)
Installation Qualification

The common requirements outlined in the "General" section are required. Additionally, product contact surfaces must be stainless steel or approved plastics or rubber.

Tanks which undergo SIP must be supplied with clean steam for sterilization. Clean steam piping is 316L stainless steel.

If the fermentor is large and is hard piped in place, the installed system is in agreement with specifications, materials and installation details shown on the PandID.

Installation Qualification Acceptance Criteria

[table=666px][tr][td]Post Installation review of PandIDs[/td][td]If the fermentor is large and is hard piped in place, the installed system is in agreement with specifications, materials and installation details shown on the PandID. Discrepancies have been marked.[/td][/tr][/table]Operational Qualification

In addition to the common requirements outlined in the "General" section, the OQ protocol will outline the following tests. Not all tests will be appropriate for a bench-top fermentor.

Not more than 1 psi (0.07 bar) is lost in ten minutes after pressurization to 10 psig (0.7 barg)

Thermocouples show that the temperature can be raised to the set point, and maintained at that setpoint. Thermocouples show that the temperature can be lowered to the set point, and maintained at that setpoint.

Calibrated fermentor instrumentation show that the growth control parameters (pH, O2, CO2) can be can be raised to their setpoints, and maintained at those setpoints, and can be can be lowered to their setpoints, and maintained at those setpoints.

The agitator performs properly; the speed can be controlled.

Empty Vessel Steam Sterilization.

[li]Thermocouples are arranged throughout the vessel, including entry points, valves and difficult to penetrate locations.[/li][li]Temperature uniformity within the chamber during steam sterilization, as shown by the thermocouples, must be less than ± 1.0°C of the mean chamber temperature. Do not include the penetration thermocouples in valves and piping in the calculation.[/li][li]Steam, during dwell in the empty chamber study, is saturated as shown by the temperature:pressure relationship (see attached graph). Do not include the penetration thermocouples in valves and piping in the calculation.[/li]Operational Qualification Acceptance Criteria

[table=666px][tr][td]Pressure Hold Test[/td][td]Not more than 1 psi (0.07 bar) is lost in ten minutes after pressurization to 10 psig (0.7 barg)[/td][/tr][tr][td]Temperature Control[/td][td]Thermocouples show that the temperature can be raised to the set point, and maintained at that setpoint.

Thermocouples show that the temperature can be lowered to the set point, and maintained at that setpoint.[/td][/tr][tr][td]Growth Parameter Control (pH, O2, CO2)[/td][td]Fermentor calibrated instrumentation shows that the various parameters can be can be raised to their setpoints, and maintained at those setpoints.

Fermentor calibrated instrumentation shows that the various parameters can be can be lowered to their setpoints, and maintained at those setpoints.[/td][/tr][tr][td]Agitation Rate[/td][td]The agitator performs properly; the speed can be controlled.[/td][/tr][tr][td]Empty Vessel Steam Sterilization[/td][td]Thermocouples are arranged throughout the vessel, including entry points, valves and difficult to penetrate locations.

Temperature uniformity within the chamber during steam sterilization, as shown by the thermocouples, must be less than ± 1.0°C of the mean chamber temperature.

Do not include the penetration thermocouples in valves and piping in the calculation.

Steam, during dwell in the empty chamber study, is saturated as shown by the temperature:pressure relationship (see attached graphs). Do not include the penetration thermocouples in valves and piping in the calculation.[/td][/tr][/table]Performance Qualification

Empty Vessel Sterilization:

[li]Bacillus stearothermophilus biological indicators are such that the product of the 'D' value and the log of the population is at least 6 (e.g., D = 1.5, population = 104). 105-106 is preferred for steam strips.[/li][li]Biological indicators enumerate within specifications per USP 23 Monograph (the " average number is not less than 50% of the number of viable spores of the specified strain per carrier stated on the label, and not more than 300% of that number" ).[/li][li]Positive control biological indicators are positive after incubation at 50-55°C for seven days.[/li][li]The sterilization cycle provides a minimum cumulative F0 of 12 minutes, at end of cycle dwell, at each temperature sensor (except the drain temperature sensor).[/li][li]All biological indicators placed are inactive after incubation at 50-55°C for seven days.[/li]

Sterilization: Vessel with Media (if appropriate).

[li]Bacillus stearothermophilus biological indicators are such that the product of the 'D' value and the log of the population is at least 6 (e.g., D = 1.5, population = 104). !05-106 is preferred for steam strips. Spore ampules are not available at 106.[/li][li]Biological indicators enumerate within specifications per USP 23 Monograph (the " average number is not less than 50% of the number of viable spores of the specified strain per carrier stated on the label, and not more than 300% of that number" ).[/li][li]Positive control biological indicators are positive after incubation at 50-55°C for seven days.[/li][li]The sterilization cycle provides a minimum cumulative F0 of 12 minutes, at end of cycle dwell, at each temperature sensor.[/li][li]All biological indicators placed are inactive after incubation at 50-55°C for seven days.[/li]

Sterile Integrity Testing.

[li]The vessel, with sterilized media,, is placed in normal operation[/li]Performance Qualification Acceptance Criteria

[table=666px][tr][td]Sterilization: Empty Vessel[/td][td]Bacillus stearothermophilus biological indicators are such that the product of the 'D' value and the log of the population is at least 6 (e.g., D = 1.5, population = 10[sup]4[/sup]). 10[sup]5[/sup]-10[sup]6[/sup] is preferred for steam strips.

Biological indicators enumerate within specifications per USP 23 Monograph (the " average number is not less than 50% of the number of viable spores of the specified strain per carrier stated on the label, and not more than 300% of that number" ).

Positive control biological indicators are positive after incubation at 50-55°C for seven days.

The sterilization cycle provides a minimum cumulative F[sub]0[/sub] of 12 minutes, at end of cycle dwell, at each temperature sensor (except the drain temperature sensor).

All biological indicators placed are inactive after incubation at 50-55°C for seven days.[/td][/tr][tr][td]Sterilization: Vessel with Media (if appropriate)[/td][td]Bacillus stearothermophilus biological indicators are such that the product of the 'D' value and the log of the population is at least 6 (e.g., D = 1.5, population = 10[sup]4[/sup]). 10[sup]5[/sup]-10[sup]6[/sup] is preferred for steam strips. Spore ampoules are not available at 10[sup]6[/sup].

Biological indicators enumerate within specifications per USP 23 Monograph (the " average number is not less than 50% of the number of viable spores of the specified strain per carrier stated on the label, and not more than 300% of that number" ).

Positive control biological indicators are positive after incubation at 50-55°C for seven days.

The sterilization cycle provides a minimum cumulative F[sub]0[/sup] of 12 minutes, at end of cycle dwell, at each temperature sensor (except the drain temperature sensor).

All biological indicators placed are inactive after incubation at 50-55°C for seven days.[/td][/tr][tr][td]Sterile Integrity[/td][td]No contamination seen in media-filled fermentor vessel when run under active conditions for a period longer than the standard fermentation.[/td][/tr][/table]