Work Shop Cleaning Assessment for Introduction of New Equipment, New Product, New Process and Changes Into Licensed Manufacturing Facilities

Transcription

1 Work Shop Cleaning Assessment for Introduction of New Equipment, New Product, New Process and Changes Into Licensed Manufacturing Facilities Sanofi Pasteur, Swiftwater, MTech Process Technology, Deputy Director Lan Zhang Aug,

2 Cleaning Assessment Acknowledge Odile Smith Director Manufacturing Technology Process Technology Sanofi Pasteur, Swiftwater, US Shawn Haynes Director Quality Validation Sanofi Pasteur, Swiftwater, US

3 Cleaning Assessment: Agenda Proposed Procedure Questions, Comments, and Recommendations The Practices in Your Company Case Study

4 Four Phase Cleaning Validation Product contact equipment cleaning validation is required for licensed manufacturing facilities. Cleaning Validation includes four phases. Assessment Phase Cycle Development Phase Cleaning Validation Phase Cleaning Validation Maintenance Phase

5 The Outcomes of the Assessment Phase Strategies and Rationales Determine the applicable cleaning cycle development and validation activities and rationales Define the critical cleaning attributes and critical cleaning parameters Calculate the acceptance criteria Generate the cleaning cycle development and validation run matrix

6 Cleaning Assessment Process Flow New Product, New Equipment, New Processes or Changes Initiate Change Control Generate Process-Equipment-Soil-Validation Matrix Decontamination/ Disinfection Requirements Equipment and Product Grouping, Worst Case Equipment Selection and Worst Case Product Selection Verify Product and Equipment Segregation Not Applicable for Cleaning Validation. Visual Inspection is required. Risk Reduction Risk Analysis and Evaluation for the Potential Contaminants of Each Equipment and Product Group Evaluate the Applicability of Cleaning Validation Applicable Determine Critical Cleaning Attributes and Cleaning ValidationAcceptance Criteria Define Critical Cleaning Parameters Determine the Applicable Cleaning Cycle Development and Validation Activities

7 Tools for Performing Cleaning Assessment Process-Equipment-Soil-Validation Matrix Risk Assessment Tool evaluate, analysis and control the risks of the potential contaminants Decision Tree a tool to determine the applicable cleaning cycle development and validation activities Run Matrix

8 Process-Equipment-Soil-Validation Matrix (Background Knowledge and the Changes)

9 Decontamination and/or Disinfection Requirements The decontamination and/or disinfection requirements shall be incorporated into the cleaning assessment, development and validation process because: Liquid chemical decontamination or hot water decontamination process may be combined with the cleaning process. In this case, the decontamination and disinfection parameters become the baseline for the cleaning development. The decontamination or disinfection process may have impacts on the cleaning process. For example, the steam decontamination process may bake the soil on equipment surface.

10 Equipment and Product Grouping, Worst Case Equipment Selection and Worst Case Product Selection The cleaning assessment was performed for each equipment and product group. The new equipment, new soil or changes are compared with the validated equipment and product group.

11 Product and Equipment Segregation Soiled equipment from different products, Soiled and clean equipment, Upstream equipment and downstream equipment, Prior to inactivation equipment and post inactivation equipment... Meet the requirements unless justifications are provided.

12 Risk Analysis Risk Identification Cleaning Assessment: Proposed Procedure Risk Identification and Analysis Equipment and Product Group: Potential Contaminant Category Live Vaccine Virus/ Bacteria /Toxin Protein, DNA/RNA, Glycoprotein, Lipoprotein, Media, etc. (inactive) Organic Chemical Ionically Charged Chemical Metal Ion Bioburde n Endotoxin Adventitious Agent, e.g. Prion Other: e.g. split agent Potential Hazard List the potential contaminants of the equipment group Source of Hazard Raw Material, Manufacturing Process, Aseptic Process Simulation, Cleaning/Decontamination/Disinfection Process, Equipment Storage Environment, Microbial organism growth during storage, Cleaning Process Hazardous Situation Situation in which product or patient is exposed to the hazard

13 Risk Identification and Analysis Equipment and Product Group:

14 Risk Identification and Analysis Equipment and Product Group:

15 Risk Identification and Analysis Equipment and Product Group:

16 Risk Reduction Determination of Cleaning Validation Acceptance Criteria Initial Cleaning Validation Acceptance Criteria Cleaning Validation Acceptance Criteria (Control Level) Cleaning Developme nt Stage Average Cleaning Validation Stage Cleaning Monitoring Stage Safety Margin Post Cleaning Actual Residue Level

17 Risk Reduction - Define the Critical Cleaning Parameters Out of limit Critical Cleaning Parameters (CCPs) may cause CCA(s) out of limit. Define the equipment cleaning process diagram. Identify the process parameters of each process step. If the process parameter failure (too high and too low) will cause a CCA out of limit, the process parameter is a CCP. The target operating range of a CCP is verified during the cleaning cycle development and/or validation. Equipment shall be designed to measure and control CCPs. Change of the CCP of a validated process shall go through Change Control.

18 Risk Reduction Determine the applicable cleaning cycle development and validation activities

19 Risk Reduction Determine the applicable cleaning cycle development and validation activities 1. New Process Equipment or Major Change 2. New No Cleaning Equipment or Major Change Refer to the previous page Equipment and Product Group: Decontamination/ Disinfection Required Cause Cleaning Process Change Refer to 5. New Cleaning Process or Changes Support data and/ or experiences for the cleaning are available. No Bench Top Cleanability Study for product ranking, establishing the initial cleaning parameters and cleaning agent selection. New Ingredient Test Method Development and Validation unless justifications are provided Cause Equipment Potential Contaminants Change Cause New Worst Case Soil No Sampling Method Development and Validation unless justifications are provided Full Scale Cleaning Cycle Development unless justifications are provided Cleaning Validation No Increased Concentration Post-cleaning Bioburden and Endotoxin level exceeds the control levels of the previous validated process No Clean/Storage Hold Time Study New Cleaning Aids or Cleaning Agents No Approval of Cleaning Aids/Cleaning Agents 3. New Product or New Potential Contaminant or Major Change New Ingredient No Cleaning Confirmation unless justifications are provided Cause New CCA or New Acceptance Criteria No Within the validated range of the existing test method No Test Method Development and/or Validation Within the validated range of the Recovery Study No Sampling Method Development and/ or Validation Change Control The existing cleaning validation results met the new acceptance criteria. No Full Scale Cleaning Cycle Development unless justifications are provided Cleaning Validation Post-cleaning Bioburden and Endotoxin level exceeds the control levels of the previous validated process No Clean/Storage Hold Time Study The new batch volume is 100% to 110% of the existing cleaning validation batch volume. Cleaning Confirmation New Cleaning Aids or Cleaning Agents No Approval of Cleaning Aids/ Cleaning Agents Cause batch volume change Increase The new batch volume is 110% to 130% of the existing cleaning validation batch volume. Cleaning Validation The new batch volume is > 130%of the existing cleaning validation batch volume. Full Scale Cleaning Cycle Development unless justifications are provided. Cleaning Validation Post-cleaning Bioburden and Endotoxin level exceeds the control levels of the previous validated process No Clean/Storage Hold Time Study New Cleaning Aids or Cleaning Agents No Approval of Cleaning Aids/ Cleaning Agents Review Cleaning Instructions. Update when needed. 4. New Manufacturing Process or Major Change Review cleaning monitoring instructions. Update when needed. Revew Cleaning Validation Inventory. Update when needed. No Cause new process equipment or major change Refer to 1. New Process Equipment or Major Change Cause new cleaning equipment or major change Refer to 2. New Cleaning Equipment or Major Change Cause new product or new potential contaminant or major change Refer to 3. New Product or New Potential Contaminant or Major Change Cause new cleaning process or major change Refer to 5. New Product or New Potential Contaminant or Major Change 5. New Cleaning Process or Major Change Critical Cleaning Process Parameter Change No Full Scale Cleaning Cycle Development unless justifications are provided. Cleaning Validation Post-cleaning Bioburden and Endotoxin level exceeds the control levels of the previous validated process No Clean/Storage Hold Time Study New Cleaning Aids or Cleaning Agents No Approval of Cleaning Aids/ Cleaning Agents Minor Change 6. No Major Equipment/ Product/Process Change Cleaning Monitoring or Cleaning Confirmation No Change

20 Risk Reduction Run Matrix for Cleaning Cycle Development and Validation

21 Cleaning Assessment: Questions, Comments and Recommendations

22 Cleaning Assessment: The Practices in Your Company

23 Cleaning Assessment: Case Study Perform the cleaning assessment for Introduction of a new product (product X) into the licensed filling and formulation facility. Currently the formulation and filling equipment is used for products A, B and C. The existing cleaning processes were validated for products A, B and C as a group. Product A was the worst case. Product X is a lower concentration of product A. New equipment or change are not required for the project. The minimum batch volume will be changed from 500L to 1000L.