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VALIDATION PROTOCOL PROCESS VALIDATION FOR CEFAKID GRANULES PROTOCOL APPROVAL Ref. No.: 010012.02/01 Page 1 / 21 Table of Contents S. No. Content Page No. 1 Objective 3 2 Scope Process Description 3 3 Abbreviations 3 4 Responsibility 4 5 Safety Precautions 5 6 Equipments/ Materials Required for the validation 5 7 Validation Study Plan 7 8 Procedure 10 9 Sampling Plan 16 10 Acceptance Criteria 20 11 Re-Validation 21 12 References 21 1. Objective: The objective of this proces validation protocol is to establish documented evidence that the processing for CEFAKID GRANULES will consistency produce a product, which meets its predetermined specification and quality attributes. 2. Scope Process Description: The prospective process validation will be performed with qualified equipment in the Betalactam non-sterile workshop with three consecutive batches of the product CEFAKID GRANULES. This process validation (PV) protocol is written in order to document that the process used in the manufacturing of the product name CEFAKID GRANULES of batch size: 150.00 kg # 50,000 sachets complies with process parameters requirement of the Batch Manufacturing Record (BMR) and finished product specifications. 3. Abbreviations: • BL - Betalactam • BMR - Batch Manufacturing Record • BPR - Batch Packaging Record • ID No. - Identification Number • IPC - In-process Control • HPLC - High Performance Liquid Chromatography • KF - Karl Fischer • Mfg. - Manufacturing • NA - Not Applicable • NMT - Not More Than • PE - Polivinyl Ethylene • PPEs - Personal Protective Equipments • PV - Process Validation • PVDC - Polyvinylidene Chloride • QA - Quality Assurance • QC - Quality Control • Q’ty - Quantity • S. No. - Serial Number • SOP - Standard Operating Procedure • SPC - Specifications and Testing Procedure • Std. - Standard • IPC - In process control 4. Responsibility: Department/ Function Responsibility Research & Development To provide the Master Formula Card to be used for the manufacture of the process batch To provide technical support during the process validation activities To coordinate and implement the process validation activities Production of BL Solid Orals Execution of BMR and protocol Providing samples wherever necessary as per the protocol and BMR Recording of observation, collection of data and filling of BMR Engineering & Maintenance To ensure that all the required utilities are working as per the respective SOPs To ensure that the related instruments and equipments are in calibrated and validated status To ensure that the environmental conditions of all the areas met the requirements QC Testing shall be done as per the sampling plan and respective specifications QA Prepare process validation protocol Sampling as per the sampling plan (IPC) Preparation and review of the Validation report, documents and its compliance to meet the acceptance criteria of the protocol 5. Safety Precautions: • Ensure that all clean-rooms and equipments are cleaned completely and sticked appropriate status labels. • Ensure that manufacturing areas is maintained under pre-defined air cleanliness with temperature between 18 – 25 o C and relative humidity not more than 55%. • Ensure that all concerned people involved are trained on all current SOPs/ SPCs and concerned practices in GMP areas during manufacturing process as well as sampling for testing. • Ensure that appropriate PPEs (i.e. safety gloves, mask, cap, goggles etc.) shall be used. • Checking the electric safety and calibration of instruments. 6. Equipment/ Materials Required for the Validation: S. No. Equipment name ID No. Qualification number Process equipments Electronic balance DI-600 22041 IOQ-22041 Electronic balance TE 1502S 22040 30111 Milling machine 22002 IQR-L-MX-1 OQR-L-MX-1 PQR-L-MX-1 Vibro sifter GY-450 22029 30011 High speed mixer 22011 30113 Stirring machine 1 22016 IQR-L-KH-1 OQR-L-KH-1 PQR-L-KH-1 Wet granulating machine 22021 IQR-L-XH-1 OQR-L-XH-1 PQR-L-XH-1 Tray dryer 22125 30124 Cubic mixer 1 22017 30104 Metal detecting machine 22027 NA Vertical sachet packing machine 1 22003 IQR-L-EG-1 OQR-L-EG-1 PQR-L-EG-1 Electronic Balance 22136 30141 Ink-jet printer 22014 IOQ-22014 IPC equipments Cylinder NA NA Electronic balance CP224S 22047 IOQ-22047 Leak-test apparatus 22050 IOQ-22050 Digital caliper 22110 NA QC Laboratory equipments Analytical Balance 25026 30023 25027 30040 25036 30042 High Performance Liquid Chromatography 25011 IQ.P-K-LC-05 OQ.P-K-LC-05 25012 IQ.P-K-LC-07 OQ.P-K-LC-07 25013 IQ.P-K-LC-08 OQ.P-K-LC-08 Titrator and Karl Fischer 25029 30086 Sieve shaker 25057 30095 7. Validation Study Plan: 7.1 Product information Product Name CEFAKID granules API/ Strength Cephalexin 250 mg Dosage Form Granule Product Code 50.C45 Batch Size 150.00 kg # 50,000 sachets Shelf Life 36 months Category Antibiotic in Cephalosporin group Label Claim Each sachet contains: Cephalexin monohydrate equivalent to cephalexin anhydrous of 250 mg 7.2 Time schedule (approx.) Batch number Date 7.3 Validation team: Member Designation QA department Manager/ officer R&D department Manager/ officer Quality control Manager/ officer Production department Manager/ officer Engineering department Manager/ officer Warehouse Manager/ officer 7.4 Manufacturing formula S. No. Raw material code Raw material Manufacturer Spec. SPC.No 1 sachet (mg) Percent (%) 1 batch (50,000 sachets) (kg) TB0C02.DSM Cephalexin monohydrate Spain In-house In-house SPC-RM-046-01 270.00 9.00 13.50 = (2 x 6.75) Corresp. to Cephalexin anhydrous) 256.80 8.56 12.84 = (2 x 6.42) VN4D01.KCP Sugar milled through 0.8 mm sieve Vietnam (KCP) EP 6.0 SPC-RM-009-01 1950.00 65.00 97.50 = (2 x 48.75) NB4A01.AJI Aspartam Ajinomoto/ Japan In-house SPC-RM-064-01 40.00 1.33 2.00 = (2 x 1.00) PH4M01.ROQ Mannitol 60 Roquette/ France In-house SPC-RM-047-01 700.00 23.33 35.00 = (2 x 17.50) AN4Q01.UNI Quinolin yellow lake Univar/ England In-house SPC-RM-074-01 0.85 0.03 0.0425 = (2x 0.02125) MY4K01.ISP PVP K29/32 ISP/ American EP 6.0 SPC-RM-040-01 30.30 1.01 1.515 = (2 x 0.7575) VN4C01.OPC 96% ethanol Vietnam (OPC) In-house SPC-RM-065-01 NA NA 20.40 = (2 x 10.20) PH4H01.EXP Apple powder flavour Expression/ France In-house SPC-RM-067-01 8.85 0.30 0.4425 Total of filled (Not including solvent) 3 000.00 100 150.00 8. Procedure: 8.1The selected validation approach is prospective validation. • First three consecutive batches of CEFAKID GRANULES are manufactured as per the authorized BMR no. 50.C45/M01/03 (for manufacturing process), the authorized BPR no. 50.C45/P01/03 (for packaging process) and it is performed validation as per specifications in protocol. • QA staff will do the sampling as per given sampling plan. The samplings will be identified i.e. batch number, stage, the number of sample, locations and sampling as per the sampling plan (refer section 11). • The samples will be analyzed by IPC/ QC as per approved testing method and approved specification. • Packaging will only be done when capsules comply with all the tests by QC. • After satisfactory analytical results, BMR and BPR will be approved by QA. • Test results and data generated during the process validation studies will be complied and reviewed at each stage of manufacturing and defined process parameters. 8.2The trials will include upper and lower processing conditions that will be encountered normally in the routine production. 8.3These trials may include worst case conditions but not necessarily simulate the failure range of the product processing conditions. 8.4A summary report will be prepared on the effect of different variables and final conclusion will be drawn on the effect of different variables on the processing of the product. 8.5Manufacturing process and sampling for validation is performed as per the follow chart Page 10 / 21