Process Validation Plan HES6403 Major Assignment

PROCESS VALIDATION SCHEME OF FILM COATED TABLET

PROCESS VALIDATION PLAN SCHEME OF

FILM COATED TABLET

TABLE OF CONTENTS

1. INTRODUCTION 1 2. OBJECTIVE 1 3. SCOPE 1 4. PROCESS DISCRIPTION 3 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 Π EXPERIMENTAL SECTION FOR TABLET COATING 15. REFERENCES

1 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

GRANULATION

DRYING OF MATERIAL

SIEVING OF GRANULES

BLENDING

COMPRESSION OF GRANULES

TABLET COATING

LABELLING AND PACKAGING

RESPONSIBILITY:-

DEPARTMENT RESPONSIBILITY Quality Assurance  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. Engineering  To install, qualify and certify all equipment, facilities as well as support system.  To develop master validation plan Quality Control  To conduct tests  Reviews protocols and reports as per requirement R & D  To design and qualify manufacturing process within specification and requirement Manufacturing  Operates and maintain all facilities, equipment and support system and manufacturing process with in specifications.

PRE-REQUISITES:

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

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

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 BATCH SIZE SCHEDULE DATE xxxxxxx LARGE xxxxxx MADIUM xxxxxxx SMALL

CRITICAL PROCESS STEPS:

Step Process risk Impact assessment assessment Dispensing Medium Non critical Sieving Higher Critical Blending Higher Critical Granulation Higher Critical Drying Higher Critical Compression Higher Critical Coating Medium Critical Labelling and Packaging Low 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 NAME OF CALIBRATION QUUALIFICATION PLAN CLEANING STEP EQUIPMENT STATUS IQ OQ PQ MONITOR VALIDATION Dispensing of Electronic Calibrated √ √ material Weighing Machine With Double Pan Milling Hammer Calibrated √ √ √ √ √ Mill/Ball Mill Blending Ribbon Calibrated √ √ √ √ √ Blender Mixing after Twin-shell Calibrated √ √ √ √ √ granulation Tumbling Mixer Granulation Fluid Bed Calibrated √ √ √ √ √ Spray Granulator Drying Try Dryer Calibrated √ √ √ √ √ Compression Rotary Tablet Calibrated √ √ √ √ √ Press Coating Fluidized Bed Calibrated √ √ √ √ √ Coater Friabilator Friabilator Calibrated √ Hardness Hardness Calibrated √ tester Tester Thickness Sliding Calibrated √ Calliper Scale Dissolution Dissolution Calibrated √ √ √ √ Apparatus Disintegration Digital Calibrated √ √ √ Disintegration Test Apparatus

CRITICAL PROCESS PARAMETERS & QUALITY ATTRIBUTES

PROCESS CRITICAL PROCESS PRODUCT PERFORMANCE STEP PARAMETER ATTRIBUTES Sieving  Size of screen  Particle size distribution  Sieving speed  Feed rate Mixing or  Mixing time  Uniformity of drug and Blending  Mixing speed excipients  Equipment capacity  Degradation  Mixing technique  Characteristic of material Granulation  Type of Technique  Flow property  Capacity  Agglomeration  Granulation speed  Degradation  Type of Binder  Size of granules  Concentration of binder  Feeding rate  Time of granulation Drying  Load size  Thermal sensitivity of  Drying technique material  Porosity of filter bags  Agglomeration  Air temperature  Air volume  Humidity of inlet/outlet air  Product temperature  Time of drying Compression  Press speed  Weight of tablet  Compression force  Thickness  Tooling  Hardness  Feed rate  Friability  Number of  Dissolution compression stations  Disintegration  Moisture of material  Content uniformity Coating  Tablet movement  Adhesion  Tablet core  Dissolution characteristics  Tensile strength  Pan design  Appearance  Pan speed  Weight of tablets  Pan load  Air quality  Air temperature  Ait humidity  Air flow  Spray rate  Spray pattern  Degree of atomization  Atomizing pressure

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

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 SAMPLING TESTING PLAN ACCEPTANCE PLAN CRIETERIA Sieving Take 3 sample  Particle size Follows BP from different distribution monograph location of the mill  Bulk density and take another  Tapped 3 samples for density retest if require Blending or Mixing Take 3 sample  Uniformity Angle of repose from top ,middle  Bulk density should be lower and bottom and  Tapped than 30° retain another 3 density for retesting if  Angle of require repose(flow property) Granulation Take 3 sample  Flow property Angle of repose from top, middle  Assay of API should be lower and bottom and 3  Bulk density than 30° another for  Tapped require retesting density 85 to 115% of APIs  Percentage compressibility  Particle size and shape Drying Take 3 sample  Loss on drying NMT 1% LOD from different  Assay of API 85 to 115% of APIs location and other 3 for retesting if require Compression 5 tables after  Thickness ± 5 % variation of (In process) each 30 mins standard value 5 tablets after  Hardness 4-6 kg/cm2

PROCESS STEP SAMPLING TESTING PLAN ACCEPTANCE PLAN CRIETERIA each 30 mins 10 tablets after  Friability NMT 1% loss of each 30 mins their weight 20 tablets after  Tablet weight ± 5 % of avg. wt each 30 mins variation 6 tablets after  Tablet Not more than 30 each 30 mins disintegration mins 5 tablets after 30  Content 85 to 115% of API mins uniformity/Ass ay of API Compression 5 tables  Thickness ± 5 % variation of (Finished dosage standard value form) 5 tablets  Hardness 4-6 kg/cm2 20 tablets  Friability NMT 1% loss of their weight 20 tablets  Tablet weight ± 5 % of avg. wt variation 6 tablets  Tablet NMT 30 mins disintegration 20 tablets after 30  Content 85 to 115% of API mins uniformity/Ass ay of API Film Coating 6 tablets  Tablet NMT 30 mins disintegration 10 tablets  Content 85 to 115 % of APIs uniformity

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

PART II

EXPERIMENTAL PLAN SECTION

TABLET COATING

Aim To demonstrate uniformity of tablet coating before packaging Procedure As per the SOP of tablet manufacturing step # 8 reference # of Experimental Minimum of 3 Runs Process Variables Pan speed 12 – 15rpm Exhaust Air Spray rate 70 to temperature 30○C 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 Process Coater ID Temperature Viscosity of Measurement TC 915 setting 30○C to solution 45○C Operator name Air pressure 30 to Time duration 50 psig Experimental Run # 1; Pan # 1 batch size large Details Run # 2; Pan # 2 batch size large Run # 2; Pan # 2 batch size small Sampling Plan Take sample at each 30 minutes. Take 20 tablets each time from top and bottom as per the Sops. Performance Adhesion test Disintegration test Appearance Parameters Wt. gain (%) Crushing strength Content uniformity Acceptance  Must fulfil all general acceptance criteria Criteria  Content uniformity 85% to 115%  Disintegration time NMT 30 min  Weight gain NMT 2 to 5% of avg. tablet weight

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 Forms- Tablets, 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 .