PROCESS VALIDATION SCHEME OF FILM COATED TABLET

PROCESS VALIDATION PLAN SCHEME OF FILM COATED TABLET

TABLE OF CONTENTS

1. INTRODUCTION 2. OBJECTIVE 3. SCOPE 4. PROCESS DISCRIPTION 5. RESPONSIBILITIES 6. PRE-REQUISITES 7. APPROACH 8. NUMBER OF RUNS & SCHEDULE 9. CRITICAL PROCESS STEP 10. EQUIPMENT AND CALIBRATION STATUS 11. CRITICAL PROCESS PARAMETER & QUALITY ATTRIBUTES 12. GENERAL ACCEPTANCE CRITERIA 13. SAMPLING AND TESTING PLAN WITH ACCEPT CRITERIA 14. PART EXPERIMENTAL SECTION FOR TABLET COATING 15. REFERENCES

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PROCESS VALIDATION SCHEME OF FILM COATED TABLET

INTRODUCTION:The following is the process validation plan for manufacturing process of XXXXXXXX(200mg) film coated tablets in pharmaceutical industry, film coated tablet coating experimental plan is also included with this. PROCESS VALIDATION PLAN FOR TABLET MANUFACTURING PROCESS:OBJECTIVE: The purpose of process validation is to provide evidence that the procedure followed by manufacturer in tablet manufacturing, is performing as per provided specification and expectations. SCOPE OF VALIDATION PROCESS Nowadays, in this expanding era of the regulatory control in pharmaceutical industry mostly concern with process validation activity based on the way of documentation and testing of product such as in process testing by this tablet manufacturer can say that their formulas and process working as per their expectation and specifications. This ensures that tablet is homogenous and reliable. Definition of process validation Process validation is the documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes. Pic/s code of GMP-Annex 15 . (2.3.4 Pics VMP)

Process description
DISPENSING OF RAW MATERIAL SIEVING AND MIXING

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

DISPENSING OF RAW MATERIAL SIEVING AND MIXING

GRANULATION

DRYING OF MATERIAL

SIEVING OF GRANULES

BLENDING

COMPRESSION OF GRANULES

TABLET COATING

LABELLING AND PACKAGING

RESPONSIBILITY:-

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

DEPARTMENT Quality Assurance RESPONSIBILITY Establishes and approval of validation protocols and reports. Manage require documents and procedures. To perform process validation by monitoring, sampling, testing, auditing of specific manufacturing process for compliance with specification and requirements. To install, qualify and certify all equipment, facilities as well as support system. To develop master validation plan To conduct tests Reviews protocols and reports as per requirement To design and qualify manufacturing process within specification and requirement Operates and maintain all facilities, equipment and support system and manufacturing process with in specifications.

Engineering

Quality Control

R&D Manufacturing

PRE-REQUISITES : Pre-requisites Qualification of critical services and utilities Qualification and calibration of equipment Qualification of facilities and environment Validation of test methods Master batch record Qualification of computer system Training of personal Documentation of CPPs Status Qualified but has been checked before process Qualified & calibrated but has been checked before process Qualified Validated but has been checked Approved Qualified Trained Documented Reference DOC# DOC # Dates Checking Expiry Date Date

DOC # DOC # DOC # DOC # DOC # DOC #

NOTE: All documents and SOPs are approved and signed by QA manager before manufacturing process.

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

APPROACHES: There are mainly three approaches for the process validation Prospective validation Concurrent validation Retrospective validation Prospective validation In this approach, validation carried out before the production of the product that intended for the sale in market. Further, in this validation, process divided in various steps. Each steps analysed experimentally or theoretically to get proper knowledge about critical process parameters and their effect on product quality. The reason to do validation by prospective approach is that before the manufacturing of tablet manufacture can predict the critical process point, their effect on product quality and manufacturer can solve obstacles which may arise during process of manufacturing. NUMBER OF RUNS & SHEDULE:For prospective validation three different batches of 200mg Film coated Tablet will be taken in to consideration. SCHEDULE FOR xxxxx FILM COATED TABLET MANUFACTURING;BATCH NUMBER xxxxxxx xxxxxx xxxxxxx BATCH SIZE LARGE MADIUM SMALL SCHEDULE DATE

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

CRITICAL PROCESS STEPS: Step Dispensing Sieving Blending Granulation Drying Compression Coating Labelling and Packaging Process risk assessment Medium Higher Higher Higher Higher Higher Medium Low Impact assessment Non critical Critical Critical Critical Critical Critical Critical Non critical

HIGHER RISK:- The step during which the severity and probability of occurrence harm to product quality, purity, uniformity is high. MEDIUM RISK:- The step during which severity or probability of occurrence of harm to Product quality, purity, uniformity is high. LOWER RISK:- The step during which severity and probability of occurrence of harm to Product quality, purity, uniformity is low. CRITICAL STEP:- The step which changes form of the product, which effect product Quality, uniformity, identity, purity.

EQUIPMENT USED AND CALIBRATION STATUS

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

PROCESS STEP Dispensing of material NAME OF EQUIPMENT Electronic Weighing Machine With Double Pan Hammer Mill/Ball Mill Ribbon Blender Twin-shell Tumbling Mixer Fluid Bed Spray Granulator Try Dryer Rotary Tablet Press Fluidized Bed Coater Friabilator Hardness Tester Sliding Calliper Scale Dissolution Apparatus Digital Disintegration Test Apparatus CALIBRATION STATUS Calibrated QUUALIFICATION PLAN IQ OQ PQ MONITOR CLEANING VALIDATION

Milling Blending Mixing after granulation Granulation Drying Compression Coating Friabilator Hardness tester Thickness Dissolution Disintegration

Calibrated Calibrated Calibrated Calibrated Calibrated Calibrated Calibrated Calibrated Calibrated Calibrated Calibrated Calibrated

CRITICAL PROCESS PARAMETERS & QUALITY ATTRIBUTES

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

PROCESS STEP Sieving CRITICAL PROCESS PARAMETER Size of screen Sieving speed Feed rate Mixing time Mixing speed Equipment capacity Mixing technique Type of Technique Capacity Granulation speed Type of Binder Concentration of binder Feeding rate Time of granulation Load size Drying technique Porosity of filter bags Air temperature Air volume Humidity of inlet/outlet air Product temperature Time of drying Press speed Compression force Tooling Feed rate Number of compression stations Moisture of material Tablet movement Tablet core characteristics Pan design Pan speed Pan load Air quality Air temperature Ait humidity Air flow Spray rate Spray pattern Degree of atomization Atomizing pressure PRODUCT PERFORMANCE ATTRIBUTES Particle size distribution

Mixing or Blending

Granulation

Uniformity of drug and excipients Degradation Characteristic of material Flow property Agglomeration Degradation Size of granules

Drying

Thermal sensitivity of material Agglomeration

Compression

Coating

Weight of tablet Thickness Hardness Friability Dissolution Disintegration Content uniformity Adhesion Dissolution Tensile strength Appearance Weight of tablets

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

PROCESS STEP CRITICAL PROCESS PARAMETER Nozzle to bed distance Viscosity of coating material PRODUCT PERFORMANCE ATTRIBUTES

GENERAL ACCEPTANCE CRITERIA: If there is, any deviation during manufacturing process it should be resolved and properly documented. All batches must meet to the product specification. By use of process capability or standard deviation process is not varies too much is checked. SAMPLING, TESTING PLAN WITH ACCEPTANCE CRITERIA PROCESS STEP Sieving SAMPLING PLAN Take 3 sample from different location of the mill and take another 3 samples for retest if require Take 3 sample from top ,middle and bottom and retain another 3 for retesting if require Take 3 sample from top, middle and bottom and 3 another for require retesting TESTING PLAN Drying Take 3 sample from different location and other 3 for retesting if require 5 tables after each 30 mins 5 tablets after Particle size distribution Bulk density Tapped density Uniformity Bulk density Tapped density Angle of repose(flow property) Flow property Assay of API Bulk density Tapped density Percentage compressibility Particle size and shape Loss on drying Assay of API ACCEPTANCE CRIETERIA Follows BP monograph

Blending or Mixing

Angle of repose should be lower than 30

Granulation

Angle of repose should be lower than 30 85 to 115% of APIs

NMT 1% LOD 85 to 115% of APIs

Compression (In process)

Thickness Hardness

5 % variation of standard value 4-6 kg/cm2

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

PROCESS STEP SAMPLING PLAN each 30 mins 10 tablets after each 30 mins 20 tablets after each 30 mins 6 tablets after each 30 mins 5 tablets after 30 mins 5 tables 5 tablets 20 tablets 20 tablets 6 tablets 20 tablets after 30 mins Film Coating 6 tablets 10 tablets NOTE: TESTING PLAN ACCEPTANCE CRIETERIA NMT 1% loss of their weight 5 % of avg. wt Not more than 30 mins 85 to 115% of API 5 % variation of standard value 4-6 kg/cm2 NMT 1% loss of their weight 5 % of avg. wt NMT 30 mins 85 to 115% of API NMT 30 mins 85 to 115 % of APIs

Friability Tablet weight variation Tablet disintegration Content uniformity/Ass ay of API Thickness Hardness Friability Tablet weight variation Tablet disintegration Content uniformity/Ass ay of API Tablet disintegration Content uniformity

Compression (Finished dosage form)

1) NMT means not more than 2) We have followed USP standards in some exemptions.

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PROCESS VALIDATION SCHEME OF FILM COATED TABLET

PART II EXPERIMENTAL PLAN SECTION

TABLET COATING

Aim Procedure reference # of Experimental Runs Process Variables

To demonstrate uniformity of tablet coating before packaging As per the SOP of tablet manufacturing step # 8 Minimum of 3 Pan speed 12 15rpm Exhaust Air Spray rate 70 to temperature 30C 100 ml/min Pan capacity 12 kg Air Flow Spray pattern Pan design Air quality Tablet movement Nozzle to bed distance Tablet core Degree of characteristic atomization Coater ID Temperature Viscosity of TC 915 setting 30C to solution 45C Operator name Air pressure 30 to Time duration 50 psig Run # 1; Pan # 1 batch size large Run # 2; Pan # 2 batch size large Run # 2; Pan # 2 batch size small Take sample at each 30 minutes. Take 20 tablets each time from top and bottom as per the Sops. Adhesion test Disintegration test Appearance Wt. gain (%) Crushing strength Content uniformity

Process Measurement

Experimental Details Sampling Plan Performance Parameters Acceptance Criteria

Must fulfil all general acceptance criteria Content uniformity 85% to 115% Disintegration time NMT 30 min Weight gain NMT 2 to 5% of avg. tablet weight

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PROCESS VALIDATION SCHEME OF FILM COATED TABLET

REFERENCE:-

I.

GENERAL REFERANCE:A) PIC/S Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation, Cleaning Validation, 1 July 2004 B) Student Manual, HES 6403 Validation Principles Year 2009, Module 4

II.

SPECIFIC REFERANCE:-

A) Bozzone, S, Process Validation of Solid Oral Dosage Forms, Part I General

Principles & Part II-Unit Operations, Part I 1 June 2001 & Part II 31 May 2001, view date 25 April 2009 Department of Health, Scottish Home & Health Department, Welsh Office, Department of Health & Social Services for Northern Ireland, British Pharmacopeia 1993, Vol II, United Kingdom B) Lachman, L, Lieberman, H, Kanig, J, The Theory and Practices of Industrial Pharmacy, Third Edition, Varghese Publishing House, Bombay, Page no 296-342 C) Lachman, L, Lieberman, H, Kanig, J, The Theory and Practices of Industrial Pharmacy, Third Edition, Varghese Publishing House, Bombay, Page no 346-372 D) Lieberman, H, Lachman, L, Schwartz, J (eds), Pharmaceutical Dosage FormsTablets, Vol 3, Second Edition, pp. 421, view date 26 April 2009 eds), Pharmaceutical Process Validation, Vol 129, Third Edition, pp. 7-29, view date 26 April 2009 E) Nash, R, Wachter, A(eds), Pharmaceutical Process Validation, Vol 129, Third Edition, pp. 159 -180, view date 26 April 2009 .

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