an ‘+ Tablet Manufacturing , Tablet Packaging Topicals Manufacturing Topicals Packaging Injectable Manufacturing Injectable Packaging Clean Liquids Packaging Cephalosparin Oral Liquid Manufacturing & Packaging and Bottle Washing Sampling Booth ‘A validation plan will be prepared with protocol which will be followed by a comprehensive validation Report Equipment Qualification: ‘The equipmentmachinery of the following sections which may affect the product quality will be validated Tablet Manufacturing Tablet Packaging Topical Manufacturing Topical Packaging Clean Liquids Manufacturing Clean Liquids Packaging Cephalosporin + Oral Liguid Manufacturing & Packaging and Bottle Washing + Samplina Booth This wil ist all the critical equipmentimachinery ofthe above sections (Appendix - IV). Separate Validation plan with protocols willbe prepared on priority basis based on risk assessment vihich willbe followed by comprehensive validation report ‘Compilation of Area Validation Report: ‘A separate validation report will be prepared for each manufacturing section mentioned above which will include: |. Validation report of building Fabrics li, Cross reference number of the validation report of utilities, environmental Condition & equipment of the respective sectionJampoulehial 8.3 Cleaning Validation: Documented evidence will be established that equipmenY machinery of the manufacturing systems are free ‘of materials, which would contaminate subsequent products beyond the acceptable lint A list of critical equipment vall be prepared and prontized (Appendix -1V) for validation on the basis of risk assessment. A detail validation plan wath protocol will describe the. 8.4 Laboratory validation: ‘The schematic validation approach may be presented as follows: Quality Control Lab Ni Microbiology Lab Critical Equipment Analytical Methods, Over view of Validation approach: Validation Master Pian ActivityFe at as execution a 1, identiies other supporting documents thal shall be prepared for specfc activites. The followin lists the types of documents generated by each activity. These documents must be assigned a unique document number, compiled, and archived as part of this VMP. ‘ca 0 apsnoval of i i a Hl Description | mM [Documents || pe Preparation for the team and related documentation and execution work. Document of VMP- Technical Specification ‘Modification 7 Preparation of Room Layout Room Specification Room Data Equipment Specification Equipment Data Utility Specification Room wise specification for utility and equipment ‘Men and Material movement Vendor Matrix Validation Plan Develop a document that describes the total objective & procedures \VMP and protocols Design Qualification Ensure that the design of the equipment complies with URS DQ Protocol and report sae || RSG bs Saga EP [icra ana ee Soe 1 eee So occ Bee aemareeescmtreaiet lec ia Preventive maintenance schedule Leste Facies, Process and cleaning erie sleet Fe Ensure that the utilities, equipment, and Process & cleaning Report aon People wil perform together to yield een acceptable process or product IAdanat PV & CV protocol Validation Summany Review of all the protocols and respective reports of various phases of validation based ‘on the findings of the review, a conclusion will Executive Summary |process || FACILITIES AN USER'S REQUIREMENT| PROTOCOL PREPARATION ¥ PROTOCOL REVIEW ¥ PROTOCOL APPROVAL| ¥ EXECUTION WORK ww REPORT ¥ EVALUATION v VALIDATION REPORTMajor break down in equipmentiutiity Modification in facility/utiity = Scheduled qualification — Periodic re-qualification 12.0 Criteria for Determining Validation ‘Validation shall be carried out for processifacility/ cleaning/ method for testing Validation shall be done when Premises Qualification The premises is a term used to encompass the individual components like the building, surfaces, HVAC system, drains, doors and windovrs and other hardware that make up the physical structure of the plant. Of these, the HVAC system is incorporated in the cntical equipment and systems list Process = New process (Technology transfer) — Change in process — Change in equipment configuration = Change in formulation — Re-validation Review (for any change) Cleaning New equipment (challenge the equipment with the worst case /difficult to clean product) equipment (any change in equipment tral if selected equipment is changed)occurances it 1 + Change in method (Pharrnacopoeial change! improvement in method) Hil + Change in instrument = Schedule review. Microbiological Methods Validation = Microbiological methods that are employed to ascertain the microbiological quality of the formulated product and hence considered critical, shall be subjected to microbiological method validation. = Amethod specific validation protocol shall be prepared and approved. The test method shail be Subjected to its validation as per the protocol. If he method meefs the acceptance criteria as outlined under this protocol then the data shall be approved and only then this validated microbiological method shall be employed for its routine microbiological testing purposes. 13.0 Acceptance Criteria Each stage of the validation process will have predetermined acceptance criteria as part of the validation protocol. These criteria can be chosen from WHO/PIC'SIGMP/CGMP guidelines. The minimum acceptance cniteria (not exhaustive) for different stages are as follow Steps Minimum Acceptance Criteria The items of equipment and systems shal comply wath + Purchase specifications + Design drawings + Engineering diagrams + Safety rules It shall b¢ checked that following documentation is provided: User manual Design Qualification (0a) + Maintenance manual + Piping and insiallation design |} Electrical schematics | i Process, and ety segram ach a f i iil ine | min |ee Checked all device calibration TTT '* Verification of HMUPLC of any display: '* Delivered undamaged and as specified. '* Installed correctly according to drawings and specifications verified. Calibrated and supported with documentation of the calibration. Operational Qualification (0Q) '* Each examined ulilily, equipment or system shall + Operate as descrited in Operations Manual + Operate as desctibed in Standard Operating Procedures. Operate throughout ail intended and worst case operating ranges Operate reliably * Meet all parameters (such as, flow rates, temperatures, pressure, speeds, control sequences) * Preparation of SOP and trained up to the operator Performance Qualification (PQ) Each examined equipment, system or process shall * Perform reproducibly according to integrated systems and its intended use * Meet all ranges, microbiological, chemical, or physical limits Process Validation (PV) Each examined process shall * Perform reproducibly according to integrated systems * New product, three consecutive batches / Existing product where validation is not performed ‘+ Meet all in-process, release, and Regulatory acceptance limits ‘Cleaning Validation Each examined cleaning process shall * Include detailed cleaning SOPs * Determination of MACO + Descrive let-to-ot cleaning (where applicable) * List of approved cleaning agents + Determination of residual/cleaning agent content Establish minimum cleaning frequency. ‘Swab/sampling and assay method validationValidation Life Cycle: ‘The Validation Life-Cycte: Validation Documentation, ops ‘The Validation Life-Cycle: Validation Maintenance: ap4 ‘The Validation Life-Cycle : Impact Assessment and Application Ops ‘The Validation Life Cycle: Design Qualification OP6 ‘The Validation Life-Cycle: Validation Review oOP7 Facility & Equipment Validation OP8 Facility & Equipment Validation OP.9 Process Performance Qualification QP-10 Process Performance Qualification P41 Process Performance Qualification : Matrix Validation P42 Cleaning Validation OP-13 Cleaning Validation Opa Validation of Analytical equipments and analytical methods TP 03 Facility Commissioning and Qualification Guide P04 Guide for production equipment, Project lifecycle and qualification USP 39/ NF 34 Standards ( 11000) and Guidelines( 100 ISPE Base Line Guide Volume §- Commissioning and Qualificationsem SITE VMP- { [ | | ‘Service & Utilities Equipment Validation | | Process Validation | | Cleaning Validation | | Laboratory Qualification Mt Nit prevents Tablet Cy | HVAC Manufacturing | ‘ac Tablet Lab Packaging Equip Lo - oat ah TT a) anr) Oral Lia Aig tnd Packaging Compressed Air (VME) Analytical Method 14 meses para 00) Topical Je--— (CHEMICAL) Vacuum (VMP) ‘Steam (VMP) Cephslesporin Environmental Method Monitoring (MICROBIAL) Capsule, Semiscba, Sof Capsule Area Validation Micro Lab Equipment Large Volume Pareotesals, Manufacturing ané | cue) Packaging\ wi mo a iu Hn mt AAT Avec chien | supported a within the Opsonin Pharma Lid_ as well as from the consultants to the project shall cary aut the \ activities. 16.4 Validation Board & Team ‘A Validation Team will be formed for each project in consultation with the Head of operations, Maintenance ‘Manager and Quality Assurance Manager. This vill comprise of representatives from Production, Engineering, Quality Assurance, Quality Control and Microbiology Manager. Additionally, required functional experts wil be nominated for inclusion into the team. Each functional area will form a validation working party to execute the activities for completion of the project within schedule. ‘The validation working party will prepare the protocols, conduct validation work, compile the data, prepare report and raise: change control where required with the support of central validation team QA Manager will approve all the protocols before ination of actives and finally approve the report after completion, 16.2 Validation Team Responsibility Fay Via Atuivia pris aeSeLaE 01 | Nomination of Validation Co-ordinator Quality Assurance Manager Head of Operations, Deputy General Manager, Plant, Managers ( Production), Deputy 02. | Formation of Validation Team Menauss Rarrosishag/ ata panbete Engineenng 03 | Preparation of a Site Validation Master plan Quality Assurance Manager er Plan for 5 BAIR ERATE FPF Seve se cr a Preparation of Validation Master Plan for i 95 _| Environmental Monitoring Microbiology & Quality Assurance 068 ei of Departmental Validation Master Production 97, | Preparation of technical specications (URS Depiity General Manager, Plant Manager Engineering Production Department & other support 98 | Prepatation of ProductiProcess Specifications | srochcto 09. | Design Qualification. Protocol & Report eater ‘Manager, Plant Manager. Installation Qualification Protocol & Report ert ARR nae Qperational Giaiineation. Protocol & Repea Beater YEE iret ESSA Validation Coordinat ane frei us TAA en if a Cea