KELUN Lifesciences Private Limited Contamination Control Strategy PDF

**OBJECTIVE:** 2. **SCOPE:** 1. Design of both the plant and processes including the associated documentation. 2. Premises and Equipment. 3. Personnel. 4. Utilities. 5. Raw Material Controls -- including in-process controls. 6. Product Containers and Closures. 7. Vendor Approval...

**OBJECTIVE:** 2. **SCOPE:** 1. Design of both the plant and processes including the associated documentation. 2. Premises and Equipment. 3. Personnel. 4. Utilities. 5. Raw Material Controls -- including in-process controls. 6. Product Containers and Closures. 7. Vendor Approval -- such as key component suppliers, sterilization of components and single use systems (SUS), and critical service providers. 8. Management of outsourced activities and availability/transfer of critical information between parties, e.g., contract sterilization services. 9. Process Risk Management. 10. Process Validation. 11. Validation of sterilization Processes. 12. Preventative Maintenance -- maintaining equipment, utilities and premises (planned and unplanned maintenance) to a standard that will ensure there is no additional risk of contamination. 13. Cleaning and Disinfection. 14. Monitoring Systems - including an assessment of the feasibility of the introduction of scientifically sound, alternative methods that optimize the detection of environmental contamination. 15. Prevention Mechanisms -- trend analysis, detailed investigation, root cause determination, corrective and preventive actions (CAPA) and the need for comprehensive investigational tools. 16. Continuous improvement based on information derived from the above. 3. **RESPONSIBILITY:** 17. 18. 19. 20. 21. 22. 4. **DEFINITION:** 5. **PROCEDURE:** 23. CCS document is a holistic overview to help readers understand the interconnectedness of all elements of the CCS and to ensure future changes do not adversely impact the state of contamination control. 24. Factual and active voice shall be used. The controls that do occur at the site shall be described. not what \"shall\" occur. The rationale for these controls shall be stated, especially when that rationale is critical to the overall strategy or not obvious / common. 25. CCS document shall consist of at most 30-50 pages. Visuals shall be included. Too many details shall be avoided; instead, reference to other detailed GMP documents (e.g., SOPs, Batch Records, site master file, reports, risk assessments) shall be given. 26. CCS document shall be prepared as per Annexure QA-069/A1. 27. The CCS shall be actively reviewed and, where appropriate, updated and shall drive continual improvement of the manufacturing and control methods. Its effectiveness shall form part of the periodic management review. 28. Following elements of contamination control strategy shall be considered during the execution of contamination control strategy: 1. **Design of both the Plant and Processes including the Associated Documentation:** 1. A short description of the design and processes including associated documentation shall be included. A plant layout & process map that identifies important plant & process contamination controls including antimicrobial agents, impurity removal steps, process hold times, and microbiological/particulate testing points shall be added. 2. An overview of how plant & process design controls the potential for microbial ingress, survival and growth/proliferation, microbial removal steps, aseptic process simulation (APS), and risk assessments and validations related to these process contamination controls shall be added. 3. Rationale for process testing scheme and limits for microbial (bio and endotoxin), viral, and particulates shall be added. 2. **Premises and Equipment:** 4. Current version of GMP drawings of facility maps with area classification outlined shall be referred. 5. An overview of facility layout showing area classifications, areas of segregation, direction of flows (e.g., upstream, downstream, warehouse, raw material sampling) shall be added. An overview of areas of enhanced biosafety levels shall be included. 6. An overview for major environmental controls: design, temperature and humidity, air pressure cascade, cleaning and disinfection, access control and facility flow, and pest control shall be added. 7. An overview of barrier technologies in equipment, if applicable (e.g., isolators, RABS) shall be included. 3. **Personnel:** 8. An overview of personnel health / hygiene / gowning requirements and associated training / certification, aseptic gowning and training, job training; highlight contamination control awareness campaign. include how visitors are handled shall be added. 9. Personnel training for visual inspection for particulates shall be included, if applicable. 4. **Utilities:** 10. An overview of controls of GMP utility systems (utilities that are used as raw material or have direct contact with product or product-contact surfaces as given below), sanitary design, usage, sanitization, and monitoring, including sampling strategy, trending system, and potential for biofilm formation shall be added. Specifically, cooling systems if placed in filling room shall be included. - Air Handling Units / HVAC - Water - Clean Steam, if applicable - Compressed Air Gas - Other Gases (e.g., nitrogen) or Vacuum, if applicable - Other GMP Utilities (e.g., cooling system), if applicable 5. **Raw Material Controls -- including In-Process Controls:** 11. An overview of raw material and components controls, including single-use systems (SUS), e.g., selection and qualification, categorization by criticality, establishing test plans and specification, receipt testing and inspection before use for consumables, and special provisions for endotoxin and / or particulate levels shall be added, if applicable. 12. What types of raw materials undergo microbiological testing and what components and SUS systems undergo in-house preparation shall be added (e.g., Depyrogenation / sterilization). 13. In-process control checks shall be included. 14. Explain how data and complaints are trended and evaluated. 6. **Product Containers and Closures:** 15. An overview of containers and closures, selection, receipt testing, in-house controls (cleaning / Depyrogenation / sterilization), and validation and control of container closure integrity shall be added. Containers used for shipment and storage of large-volume solutions and final-product containers shall be included. 7. **Vendor approval -- such as key component suppliers, sterilization of components and single use systems (SUS), and critical service providers:** 16. An overview of vendor or subcontractor approval for raw material and consumables, Depyrogenation / sterilization of components and SUS systems, or other outsourced services related to contamination control shall be added (e.g., cleaning and sterilization services). 8. **Management of outsourced activities and availability / transfer of critical information between parties, e.g., contract sterilization services:** 17. A description on management of outsourced activities and availability / transfer of critical information between parties. 9. **Process Risk Management:** 18. Process risk assessment shall be done as per SOP QA-008 and details of process risk assessment shall be included in the CCS document. 10. **Process Validation:** 19. Process validation shall be carried out as per SOP QA-015 and details of process validation shall be included in the CCS document. 11. **Validation of Sterilization Processes:** 20. An overview on APS program and outcome shall be added in the CCS document. 12. **Preventative Maintenance -- maintaining equipment, utilities and premises (planned and unplanned maintenance) to a standard that will ensure there is no additional risk of contamination:** 21. An overview of equipment maintenance program, including how PM schedules (planned) are established and how maintenance events are contained to limit contamination to the process shall be added. 22. An overview of unplanned maintenance and how maintenance events are contained to limit contamination to the process shall be added. 13. **Cleaning and Disinfection:** 23. An overview of reusable manufacturing equipment controls: segregation of clean / dirty (and live / non-live, toxic / detoxified, where applicable); cleaning and sanitization / sterilization methods, including water quality; clean equipment storage; column / skid and UF/DF handling; and associated validation and risk assessment related to contamination control shall be included. 14. **Monitoring systems - including an assessment of the feasibility of the introduction of scientifically sound, alternative methods that optimize the detection of environmental contamination:** 24. An overview of environmental monitoring, limits, and status of environmental qualification and periodicity of requalification shall be added. 25. An assessment of the feasibility of the introduction of scientifically sound, alternative methods that optimize the detection of environmental contamination, if any shall be included. 15. **Prevention mechanisms -- trend analysis, detailed investigation, root cause determination, corrective and preventive actions (CAPA) and the need for comprehensive investigational tools:** 26. An overview of quality systems related to contamination control (e.g., deviation investigation, trending, CAPA, change control, quality risk management) shall be included. Description on how these quality systems is employed to strive for continuous improvement of the contamination control program shall be added. 16. **Continuous improvement based on information derived from the above:** 27. Any action plans proposed based on the information from the review shall be included as a continuous improvement program. 6. **ABBREVIATIONS:** 7. **DISTRIBUTION:** **Master Copy** **Controlled Copy** **Display Copy** ------------------- --------------------- ------------------ Quality Assurance Quality Assurance NA Production NA Quality Control NA Microbiology NA Engineering NA Stores NA 8. **ANNEXURES:** **Sr. No.** **Annexure No.** **Footer No.** **Title of Annexure** **Mode of Usage** ------------- -------------------- ---------------- ----------------------------------------- -------------------------- 1 Annexure QA-069/A1 F/QA-069/01-01 Contamination Control Strategy Document **Use as Specimen Copy** 9. **REFERENCES:** Annex-I of EudraLex Volume 4 Part I: Manufacture of Sterile Medicinal Products 10. **REVISION HISTORY:** **Sr. No.** **Version No.** **Ref. Change Control Number** **Details of Revision** ------------- ----------------- -------------------------------- ------------------------- 1 01 CC2024-018 New SOP