STANDARD OPERATING PROCEDURE

Transcription

1 Document No.: SOP-XXXX Revision: XX Page 1 of OBJECTIVE 1.1 To comply with the requirement of policy XYZ on revalidation/requalification. 1.2 To outline the procedure by which the Validation Services Department periodically evaluates the performance of previously validated facilities, equipment, systems, and processes. This evaluation includes a periodic review of performed critical changes/repairs. Reviews will be performed to determine the impact to the validated state of the facilities, equipment, systems, and processes. The objective of the program is to verify that systems continue to operate within the criteria established in the original validation and according to current Company guidelines. 2. SCOPE 2.1 This procedure applies to previously validated facilities, equipment, systems, and processes that are used to manufacture or to support the manufacture of pharmaceutical products intended for clinical or commercial distribution at XXXXX facilities Planned and emergency changes to validated facilities, equipment, systems, and processes are documented and evaluated via the Change Control system (SOP- XXXX). 2.2 Critical changes/repairs to facilities, equipment, systems, and processes are documented in the Critical Changes/Repairs database (e.g., Maximo, EQMS). Review of the database involves identifying the Critical Change/Repair performed by equipment name, service manager, system association, technician, ID number, work order number, or author. The database includes Changes/Repairs from Buildings 001, 002, 003, and REFERENCES The Critical Change Review (CCR) will include applicable Change Control, Preventive Maintenance Interval Evaluation, Maintenance Work Orders, and Quarterly EM Trend Report Review (where applicable). 3.1 SDSOP-XXXX 4. RESPONSIBILITY 4.1 The Validation group is responsible for verifying that facilities, equipment, systems, and processes used in the manufacture of product for clinical or commercial distribution remains in a validated state. 4.2 The Validation group maintains a system that is capable of providing notification when critical validated facilities, equipment, systems, and processes requires requalification. 4.3 The Validation group is responsible for generation of a protocol and final report per SOP- XXXX to obtain approval and documented evidence of the requalification activities. SOP- XXXX provides guidance on the responsibility of the Validation Department and approval of the protocol and final report. 4.4 Validation, Quality Assurance (QA), and identified impacted departments are responsible for reviewing the summary reports and taking the appropriate actions as requested.

2 Document No.: SOP-XXXX Revision: XX Page 2 of DEFINITIONS 5.1 Key Performance Test A functional challenge that is indicative of the operation or performance of the particular system typically a part of the qualification. Performing a key performance test during the system requalification enables a more direct comparison of the current system operation relative to the validated state. These are identified in the applicable requalification procedures and protocols. 5.2 Last Significant Data Point Either the date of last data generated or the date of the reviewed lab test results. 5.3 Routine Periodic Recertification HEPA filters inside controlled areas are recertified following established schedules per SOP-XXXX Classified rooms/areas are recertified following established schedules per SOP-XXXX. 5.4 Revalidation/requalification are validations/qualifications performed as part of continued process verification to assure that the facilities, utilities, equipment and process remains in a state of control after changes or accumulated changes have been made or observed, or after certain period of time. At a minimum, the revalidation/requalification plan is to include a review of change control since the last validation, and functional challenge of the appropriate critical process variables or a review of routine monitoring as applicable. 5.5 User The functional area that principally utilizes, or is responsible (Owner) for, the equipment or facility. 6. PROCEDURE 6.1 General Once facilities and/or equipment have been validated, they are considered to be in a state of control. If validated conditions and control parameters remain unchanged, the system continues to operate in a validated state It is important for any significant change to be recognized and assessed before or at the time it occurs (refer to SOP-XXXX) so that appropriate action(s) can be taken to maintain a validated state Depending upon the assessment no additional validation or revalidation may be judged as necessary to demonstrate the suitable ongoing state of control for a given system Prospective testing is performed when something about the process, materials, equipment, operating parameters, or procedures, originally validated, has significantly changed in such a way as to put the validity of the validation work in question relative to the new status.

3 Document No.: SOP-XXXX Revision: XX Page 3 of CCR The Validation group performs CCR for major equipment, processes, and/or systems and summarizes the results in a CCR report. In instances where several changes were made in which each was identified separately to have "no impact" to the validation, the collective changes will be reviewed to reassure that a validated state has been maintained. These reviews may also initiate additional testing or data gathering activities (e.g., another change control) up to and including, when appropriate, a comprehensive revalidation As part of routine scheduled requalification, it is preferable that the CCR is performed prior to testing activity execution Access the Critical Changes/Repairs database and select the method for identifying the critical changes/repairs for the equipment, process and/or system that requires a review to be performed Review the critical changes/repairs that were performed during the period of the review that are not PM based (i.e., corrective work orders). Review the database list for the specified equipment, process, and/or system selected and obtain a copy of each Critical Change/Repair and associated Maintenance Work Order (MWO) performed Include in the review how many MWOs were generated and what they were for. Compare the number of MWOs and critical changes/repairs to determine the collective impact (if any) to the equipment, process, and/or system. Include this data in the summary report Determine if there were any related validation protocols, protocol addenda, and/or studies performed during the period of the review and assess relationship (if any) to any review trends Determine if there are any trends to the type and number of MWOs and critical changes/repairs that have occurred. If a trend is identified, discuss the findings with the impacted departments and QA to determine the appropriate action(s) to be taken. This data will be included in the summary report In the case of Preventative Maintenance (PM) work orders, determine if the applicable PM task(s) intervals are sufficient and make recommendations as needed based on work order history review Review pertinent quarterly EM trend reports, where applicable, to determine potential impact due to events against the equipment or system under review Review and evaluate the critical changes/repairs performed and determine the collective impact to the equipment, process and/or system (per SOP-XXXX) Generate a summary report that will consist of, but not be limited to, a summary of change control and/or MWO files reviewed, and evaluation of quarterly EM trend reports (if applicable).

4 Document No.: SOP-XXXX Revision: XX Page 4 of The summary report to be generated may be a stand-alone document, with its own distinct protocol number, or part of a revalidation package If the summary report identifies any adverse impact to the validated state of a process, environment, equipment, or utility, contact the impacted department(s) and QA to determine the appropriate action(s) to be taken When applicable, responsible individuals from impacted departments review the summary report to assess collective impact to their respective programs. 6.3 Revalidation For example, Maintenance reviews the summary report to assess any impact to the Maintenance programs (e.g., change in PM interval) For example, Engineering reviews the summary report to assess any impact to the Engineering programs (e.g., Engineering design or drawings) At the discretion of the Validation Services management, systems may be subjected to revalidation testing to address instances where the original (or previous) validation does not comply with current company and regulatory guidelines The need for revalidation may also be triggered by any of the following: The Change Control Program has determined that revalidation is necessary as a result of a change to a facility, equipment, system, or process An audit of the facility, equipment, system, or process indicates that revalidation is necessary An equipment-related Event investigation indicates that the operational state of the system may not be consistent with the original validation An assessment is performed every three years covering a six-year review period for all revalidation using the three-year revalidation module, with the exception of chambers where the review period currently covers only two years. The purpose is to determine if the totality of these minor changes impact the validate state of critical utilities, equipment, and systems The format, issuance, tracking and approval of validation protocols are described in SOP-XXXX. 6.4 Periodic Requalification Requalification of critical facilities, equipment and processes described in this procedure (i.e., with the greatest potential for product impact) is performed periodically beyond any revalidation resulting from change control.

5 Document No.: SOP-XXXX Revision: XX Page 5 of Requalification of equipment that is on a rotational basis (e.g., Building 001 Manufacturing autoclaves) is performed whereby system performance testing is scheduled for one unit which then triggers critical change review for the duplicate item to be performed at the same time Requalification activities may include prospective and/or concurrent testing, and/or a retrospective review of system performance data. The retrospective review should indicate that previous validation efforts meet current company standards, effective quality systems are in place, and effective change control is in place (e.g., via SOP-XXXX). Prospective or concurrent testing is performed to demonstrate that the system operation continues to be in a validated state of control If any test, acceptance criteria, or protocol requirement is not met, the activities are halted (as applicable) and deviation is generated in accordance with SOP-XXXX. 6.5 Requalification Schedule The management of Validation Services establishes the schedule to re-qualify a facility and equipment. Requalification is performed individually on a facility and equipment basis. When there are multiple pieces of equipment with identical functionality, testing is required for each piece of equipment unless there is an approved justification to utilize a bracketing or rotational approach. The CCR aspect, at minimum, should couple the piece of equipment being function tested The schedule for requalification is established based upon the critical nature of the facility and equipment in question and regulatory requirements. Without the documented approval of at least the system owner, Validation, and QA, the time period between requalification of the systems described in this procedure does not exceed the time specified in this procedure The requalification date is derived from the last significant data point in the current Validation review In the case of a CCR, the requalification date is derived from the QA approval date of the review The requalification schedule should allow for a 45 day review window, which includes the requalification testing, Validation review, and final report approval The appropriate Requalification review schedules (i.e., one-year or three-year Requalification) are added in database XYZ according to the frequency identified for facilities and equipment The testing specified for requalification may be conducted in conjunction with, or as part of, a separate CRRA or validation protocol. The evaluation of a change control may be on a different schedule from the documentation review but cannot exceed the frequency specified in this procedure to satisfy the requalification requirements.

6 Document No.: SOP-XXXX Revision: XX Page 6 of Requalification Execution The Validation Services Department prepares requalification forms (per appropriate SOP) or protocol (as needed) for the facility or equipment system in question prior to test execution Steam sterilization, depyrogenation and chamber requalification are executed per approved SOPs The minimum protocol requirements for critical systems are defined in the protocol and are approved per SOP-XXXX (which includes Quality Assurance) Any revisions to the approved protocol are subject to review by original signatories Requalification activities are executed under the direction of the Validation Department The requalification data are assembled and summarized in a final report by Validation Services. The report, executed protocol (as appropriate), and test data are submitted to the management of Validation Services or designee for review and approval Deviations and exceptions from the protocol procedure or acceptance criteria are documented in the final report The completed requalification final report is submitted for review and final approval. The approved final report is filed with the original validation package An assessment of the control system [i.e., PLC (programmable logic controller), data logger, MMI (man-machine interface)] for the system in question is performed according to SOP-XXXX and included in the requalification plan Critical Alarm(s) simulation will be performed (where applicable) as part of the requalification to verify functionality. Execution will follow pertinent forms per the individual procedures. 6.7 Requalification of Individual Systems Sterilization Systems Autoclaves and Dry Heat Ovens In addition to the annual autoclave Requalification all current autoclave commercial load configurations are individually requalified biennially (every two years). Each load is challenged using biological indicators (BIs) that are placed inside the load adjacent to the thermal sensor, e.g., thermocouples The requalification plan includes a review of related events, work orders, and change control documents generated for the equipment since the last validation/requalification Autoclave requalification function tests are performed in accordance with SOP-XXXX. The plan for autoclaves includes an empty chamber thermal distribution study to verify chamber temperature uniformity, and

7 Document No.: SOP-XXXX Revision: XX Page 7 of 12 an extended vacuum leak challenge to verify chamber seal integrity. The results of the requalification study are assessed with the data from the previous requalification, original, or most current validation for consistency In conjunction with the autoclave revalidation, an air removal test is performed at the beginning and end of the study and reviewed Depyrogenation ovens/tunnel requalification function tests are performed in accordance with SOP-XXXX. The requalification plan for depyrogenation ovens/tunnel includes a single loaded chamber heat distribution/penetration test run performed consistent with the original validation or most current requalification. The run includes endotoxin challenges that are placed inside the chamber adjacent to the thermal sensors. The results of the requalification study are assessed with the data from the previous requalification, original, or most current validation for consistency Steam-In-Place (SIP) Process The requalification of depyrogenation ovens/tunnel includes the acceptable integrity test results of the HEPA filters, if applicable In addition vial washing requalification is performed as part of the system since vial washing is always done concurrent with vial depyrogenation Each SIP process is evaluated annually (i.e., for tanks and lyophilizers). The thermal mapping/bi challenge must be repeated such that the locations are consistent with the most recent PQ Each equipment item is challenged annually e.g. each tank, each lyophilizer The requalification plan includes a review of related events, work orders, PM, and change control documents generated for the equipment since the last validation/ requalification The plan includes a single test run performed consistent with the original validation. The run includes biological indicators (BI) that are placed inside the system adjacent to the thermal sensors, e.g., thermocouples. At the end of the BI challenge, the BI Test must be performed within 4 hours. The results of the requalification study are assessed with the data from the previous requalification, original, or most current validation for consistency Controlled Temperature Storage Chambers/Warehouses Controlled storage chambers used to house in-process samples, finished product, stability samples, and/or approved components are evaluated every year for walk-in refrigerator and every two years for the

8 Document No.: SOP-XXXX Revision: XX Page 8 of 12 remainder (freezers and incubators). The evaluation includes a CCR and requalification. Chambers are qualified or requalified per SOP-XXXX, where temperature mapping (and humidity mapping as required) is performed along with review of related events, work orders, and change control documents generated for the equipment since the last validation/ requalification. Upon completion of any of the above procedure, summarize the data for the chamber (including hot and cold spot assessment) in a Final Report Controlled Storage Warehouses used to house in-process samples, finished product, stability samples, and/or approved components are evaluated every two years. The evaluation includes a CCR and requalification. Warehouses are qualified or requalified per SOP-XXXX, where temperature mapping (and humidity mapping as required) is performed along with review of related events, work orders, and change control documents generated for the equipment since the last validation/ requalification. Upon completion of any of the above procedure, summarize the data for the warehouse (including hot and cold spot assessment) in a Final Report If the requalification mapping results are acceptable and the CCR indicates no trends impacting the chamber/warehouse performance then the requalification is summarized and routed for approval. If the requalification mapping results are not acceptable or the CCR indicates a trend with potential impact to the chamber performance then an evaluation is performed. If the identified root cause requires a repair or adjustment impacting the chamber performance (temperature/humidity control or distribution) it must be documented by a work order and/or change control, and the requalification mapping must be repeated. The activities and results are summarized in the final report Controlled Manufacturing Areas (HVAC) HVAC systems are evaluated every three years, with a review period that covers six years. The cumulative review period is integrated into the CCR review period wherein a six-year time frame is evaluated The requalification plan includes a review of related events, work orders, and change control documents generated for the equipment since the last validation/ requalification A review of environmental monitoring data are included as part of Room Qualifications A comparison of the baseline and current HVAC Variable Frequency Drive (VFD) set point parameters is performed during requalification activities. An assessment of the state of control for the associated VFD set point parameters is performed.

9 Document No.: SOP-XXXX Revision: XX Page 9 of Critical Utility Systems WFI, RO Water, Pure Steam, CDA, Nitrogen Critical utility systems are evaluated every three years, with a review period that covers six years. The cumulative review period is integrated into the CCR review period wherein a six-year time frame is evaluated The requalification plan includes a review of related events, work orders, PM, and change control documents generated for the equipment since the last validation/ requalification Review the results of recent environmental monitoring for evidence of trends or routine excursions that may indicate a loss of system control. This review may be performed by Quality Control Microbiology as part of the review of environmental monitoring Clean steam attributes are confirmed annually Packaging Line Packaging lines are reviewed and evaluated annually for their impact on the validated processes The requalification plan includes a review of work orders, and change control documents generated for the equipment since the last validation/ requalification. A review of the packaging process as compared to the original process validation is also included as appropriate The equipment train includes all the major equipment on the packaging line Continued Verification of Process Validation Media Fill To maintain the state of control, continued verification of validated processes is performed annually. The continued verification of a process is performed for processes with an approved Standard Process Parameters (SPP) document The collective impact from change control, work orders, and events since the last validation or verification are reviewed in terms of their collective impact on the process performance. Revalidation can be performed as needed As part of continued verification, review the in-process data against the SPPs to evaluate process stability and capability As part of the process validation review, the process equipment train includes a review of the major equipment not already covered in this procedure Review of the process validation is segmented based on the processes listed in approved SPP documents.

10 Document No.: SOP-XXXX Revision: XX Page 10 of Media fills are reviewed annually to assess the current line configurations for the aseptic process The aseptic process is reviewed Commercial lots should be trended as part of the continued verification process, at minimum, to include the following items to ensure that the media fill program and commercial process are aligned: Sterile Hold Times Fill Duration Corrective Interventions Batch Size The trending data is captured from documents such as the MPRs and filling event log Room Qualification Classified rooms are periodically recertified and summarized Recertification/Requalification of existing/modified classified rooms includes, if applicable: A measurement of room air volumetric flow (air changes per hour) Air velocity (unidirectional flow areas only) HEPA filter leakage as appropriate Date of HEPA replacement and next due date for controlled areas Temperature, relative humidity, and room to room differential pressure A separate CCR is not required for classified rooms as environmental monitoring results to determine if an environment has drifted outside its normal operating range are trended and summarized Cleaning Validation Routine cleaning monitoring is performed and the frequency is governed per SOP-XXXX A review of the CIP process as compared to the original validation is also included as appropriate.

11 Document No.: SOP-XXXX Revision: XX Page 11 of ATTACHMENTS 7.1 Requalification Schedule 8. REVISION HISTORY Rev. XX Summary of Changes Update continue verification of process validation section to align with standard process parameters document. Delete process that has no SPP document on Attachment 7.1.

12 Document No.: SOP-XXXX Revision: XX Page 12 of 12 Title: REVALIDATION OF SYSTEMS, EQUIPMENT, AND PROCESSES Attachment 7.1 The systems listed in the table below is intended to be a representation of types of equipments or systems incorporated into the requalification schedule at the site. BUILDING TYPE CURRENT SYSTEMS REQUALIFICATION SCHEDULE REFERENCE DOCUMENTS Steam Sterilization Autoclaves Lyophilizer Tank SIP Annually 002 Dry Heat Depyrogenatio n Dry Heat Oven Depyrogenation Tunnel Annually HVAC HVAC & Critical Utilities RO WFI PS Nitrogen 3 years (Note: this CCR covers a 6 year review period) CDA