Cleaning Validation Systems CIP COP Manual How to get to Validation

Transcription

1 Cleaning Validation Systems CIP COP Manual How to get to Validation

2 First: Know and Understand the Soils and Residues You Must Clean

3 Virus 3

4 Raw Meat and Prions 4

5 Formalin Sodium Citrate Sucrose Triton X-100 Aluminum Mercury 5

6 Microcarriers 6

7 Allantoic Fluid 7

8 Your Soils may Change with Heat/pH/Time 8

9 Evaporative Dispersion 9

10 Evaporative Dispersion 10

11 Gelatin 11

12 Antifoam 12

13 Bacteria Gram-positive bacteria Gram-negative bacteria are pathogenic, meaning they can cause disease in a host organism. This pathogenic capability is usually associated with certain components of Gramnegative cell walls, in particular the lipopolysaccharide (also known as LPS or endotoxin) 13

14 Endotoxin 14

15 Viral Material after Cleaning and/or Disinfection Resulting Vaccine - Split Virus Resulting Material after cleaning with cleaning detergents or disinfectants (to be demonstrated through degradation studies) 15

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17 Second: Know and Understand the Equipment you Must Clean

18 Product Contact Equipment VS Equipment that is Contacted by Product

19 Biologically Active Material BAM live or inactivated vaccines (intermediates, bulk and final product) that have a potential to engender an immune response. BAM Contact Surfaces Condition 1: Equipment surfaces that are in direct contact with biologically active material (BAM) during manufacturing activities. During the production and cleaning processes, these surfaces are soiled with BAM, product components (e.g., buffers, media, etc.) and cleaning agents. The cleaning must be validated to show removal of soils. Condition 2: Equipment surfaces that are not contacted by BAM by design but may contact BAM in practice (due to splashing or spillage) will be individually assessed to determine the risk involved should the surfaces not be sufficiently cleaned and/or sterilized before contact is made.

20 Non-BAM Contact Surfaces Condition 1: Equipment surfaces used for preparing and/or transferring reagents, medias, buffers, components (e.g., stoppers) etc. that are incorporated into the product. During the production and cleaning processes, these surfaces are soiled with product components and/or cleaning agents but are not soiled with BAM. The cleaning must be validated to show removal of these soils. Condition 2: Equipment surfaces that are not contacted by reagents, medias, buffers, components by design but may contact reagents, medias, buffers, components in practice (due to splashing or spillage) will be individually assessed to determine the risk involved should the surfaces not be sufficiently cleaned and/or sterilized before contact is made.

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26 Third: Know and Understand the Cleaning Processes you must Validate

27 Understand the Manufacturing Process Processing Stage 1 - those phases of a manufacturing process that precede the purification steps. Stage 1 process equipment includes the preparation of raw materials, the fermentation or culture process and primary filtration steps. Processing Stage 2 - those phases of a manufacturing process involving product purification and conjugation up to but not including final formulation Processing Stage 3 - those phases of a manufacturing process involving final formulation and filling

28 Know the Cleaning Systems Utilized Clean-in-Place (CIP): The process of cleaning a piece of equipment, piping, or device without taking it out of line; cleaning performed without the need to relocate the equipment being cleaned(may be manual or automated.) Clean-Out-of-Place (COP): The process of cleaning a piece of equipment, piping, or device after it has been taken out of line (may be manual or automated.) Cabinet Washer alternately described as a glass or bottle washer - is a compartment type pressure washer with doors that is designed to utilize racks, spray nozzles, cleaning solutions and air to clean and dry the interior and exterior of items placed within its chamber. Manual Cleaning - Manual cleaning is performed by trained personnel who follow detailed procedures pertaining to preparation and use of cleaning solutions, disassembling, scrubbing using non-abrasive and non-shedding brushes or pads, soaking, rinsing and drying.

29 Sonicators

30 Sonicators 30

31 S o n i c a t o r s 31

32 Sonicators 32

33 P a r t s W a s h e r 33

34 Parts Washer 34

35 Parts Washer 35

36 P a r t s W a s h e r 36

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40 Racks and Loads Rack 01A, Load 1 MYO Rack 01A, Load 2 MYO

41 Racks and Loads Rack 01B, Load 1 MYO Rack 01B, Load 2 MYO

42 Racks and Loads Rack 02, Load 1 MYO Rack 02, Load 2** MYO ** Incorrect image

43 Racks and Loads Rack 03, GCB Rack 04, Load 1 45 EP

44 Racks and Loads Rack 04, Load 2 45 BP Rack 05A, TSH

45 Racks and Loads Rack 05B, TSH Rack 06A Load 1, TSH

46 Racks and Loads Rack 06A Load 2, TSH Rack 06B, TSH

47 Racks and Loads Rack 07, SS (MYO+TSH) Rack 08A, CC (MYO+TSH)

48 Racks and Loads Rack 08B Load 1, CC (MYO+TSH) Rack 08B Load 2, CC (MYO+TSH)

49 Racks and Loads Rack 09 Load 1, BRX (MYO+TSH) Rack 09 Load 2, BRX (MYO+TSH)

50 Racks and Loads Rack 10 Load 1, Mueller (Gen Media) Rack 10 Load 1, Walker (Seed MYO+TSH)

51 Racks and Loads Rack 10 Load 3, Feldmeier (Gen Media) Rack 10 Load 4, Shipper (TSH)

52 Racks and Loads Rack 11, 51 Gen MP Rack 12, 51 Gen EP + EX

53 Racks and Loads Rack 13, Gen EP Rack 14, 51 MP / 45 BP

54 Racks and Loads Rack 15, 51 Gen MP

55 Vial Washer 55

56 Vial Washer 56

57 Clean In Place Skid (CIP) 57

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59 CIP Flow Example Rinse Conductivity Sensor To drain Recirculation or Balance Tank Fill WFI Final Rinse once thru P Pressure indicator Temperature indicator Temperature transmitter Flow Switch CIP Rinse Sample Point CIP Storage F CIP Target Clean Compressed Air To drain Balance tank CIP Centrifigal Supply pump Flow Control Valve Heat Exchanger Rinse Conductivity Sensor (select transfer lines) CIP Rinse Sample Point (select transfer line) CIP Liquid Ring Return Pump To drain 59

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62 CIP Cycle Description 62

63 Manual Clean 63

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66 Manual Clean 66

67 Manual Clean 67

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69 Fourth: Know and Understand the Acceptable Philosophy at your Site

70 Your Quality Counterpart

71 Your Quality Counterpart

72 Method Approach - Direct cleaning validation execution is performed on subject equipment and residues. Method Approach Matrix - cleaning validation execution is performed on equipment and/or residue that is grouped or bracketed to minimize the amount of runs while still providing evidence that all specified equipment cleaned will be in a validated state. If the matrix method is utilized the grouping strategy and the rationale for the grouping must be justified in the project plan and/or the protocol. Parent - when using the matrix approach the item chosento represent the group or bracket is termed theparent (typically the worst case or most challenging item). Child/children when using the matrix approach the item(s) identified as belonging to a group.

73 Confirmation when applying the matrix approach, the act of executing one (1) successful cleaning validation run on equipment categorized as a child. When applying confirmation runs to the family approach, the cleaning process is considered validated after the parent cleaning validations are executed. Verification A one-time testing of equipment for cleaning efficacy. Verifications may be performed during Demonstration, Definition and/or Consistency runs, or after process changes/deviations where the validated cleaning no longer applies (eg, violation of dirty hold time) prior to performing cleaning validation. Validation - Validation can be described as establishing documented evidence that provides a high degree of assurance that a specific process/equipment will consistently produce a product meeting its predetermined specifications and quality attributes.

74 Acceptance Criteria Required Testing Definition of Failure Degradation Studies Analytical Methods and Recoveries Filing Strategy Company 5 year and 10 year plan for the site Routine Monitoring Revalidation

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