PROCESS VALIDATION SCHEME OF FILM COATED TABLET
PROCESS 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
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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 2
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:-
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PROCESS VALIDATION SCHEME OF FILM COATED TABLET DEPARTMENT
RESPONSIBILITY
Quality Assurance
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Engineering
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Quality Control
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R&D
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Manufacturing
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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.
PRE-REQUISITES : Pre-requisites
Status
Reference
Qualification of critical services and utilities Qualification and calibration of equipment
Qualified but has been checked before process Qualified & calibrated but has been checked before process Qualified
DOC#
Qualification of facilities and environment Validation of test methods Master batch record Qualification of computer system Training of personal Documentation of CPPs
Dates Checking Expiry Date Date
DOC #
DOC #
Validated but has been checked Approved Qualified
DOC # DOC # DOC #
Trained Documented
DOC # DOC #
NOTE: All documents and SOPs are approved and signed by QA manager before manufacturing process .
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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
BATCH SIZE
xxxxxxx xxxxxx xxxxxxx
LARGE MADIUM SMALL
SCHEDULE DATE
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PROCESS VALIDATION SCHEME OF FILM COATED TABLET CRITICAL PROCESS STEPS: Step
Process risk assessment
Impact assessment
Dispensing Sieving Blending Granulation Drying Compression Coating Labelling and Packaging
Medium Higher Higher Higher Higher Higher Medium Low
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
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PROCESS VALIDATION SCHEME OF FILM COATED TABLET PROCESS STEP
NAME OF EQUIPMENT
CALIBRATION STATUS
Dispensing of material
Electronic Weighing Machine With Double Pan Hammer Mill/Ball Mill Ribbon Blender Twin-shell Tumbling Mixer Fluid Bed Spray Granulator Try Dryer
Calibrated
QUUALIFICATION PLAN IQ OQ PQ MONITOR √ √
Calibrated
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Calibrated
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Calibrated
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Calibrated
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√
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Calibrated Calibrated
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Calibrated
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Milling Blending Mixing after granulation Granulation
Drying Compression Coating Friabilator Hardness tester Thickness Dissolution Disintegration
Rotary Tablet Press Fluidized Bed Coater Friabilator Hardness Tester Sliding Calliper Scale Dissolution Apparatus Digital Disintegration Test Apparatus
Calibrated Calibrated
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Calibrated
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Calibrated
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Calibrated
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CLEANING VALIDATION
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CRITICAL PROCESS PARAMETERS & QUALITY ATTRIBUTES
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PROCESS VALIDATION SCHEME OF FILM COATED TABLET PROCESS STEP Sieving
CRITICAL PROCESS PARAMETER • • •
Mixing or Blending
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Granulation
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Drying
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Compression
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Coating
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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 •
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Particle size distribution
Uniformity of drug and excipients Degradation Characteristic of material Flow property Agglomeration Degradation Size of granules
Thermal sensitivity of material Agglomeration
Weight of tablet Thickness Hardness Friability Dissolution Disintegration Content uniformity Adhesion Dissolution Tensile strength Appearance Weight of tablets
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PROCESS VALIDATION SCHEME OF FILM COATED TABLET PROCESS STEP
CRITICAL PROCESS PARAMETER • •
PRODUCT PERFORMANCE ATTRIBUTES
Nozzle to bed distance Viscosity of coating material
GENERAL ACCEPTANCE CRITERIA: •
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•
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 PLAN
Sieving
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
Blending or Mixing
Granulation
Take 3 sample from top, middle and bottom and 3 another for require retesting
TESTING PLAN •
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Drying
Compression (In process)
Take 3 sample from different location and other 3 for retesting if require 5 tables after each 30 mins 5 tablets after
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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
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Thickness
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Hardness
ACCEPTANCE CRIETERIA Follows BP monograph
Angle of repose should be lower than 30°
Angle of repose should be lower than 30° 85 to 115% of APIs
NMT 1% LOD 85 to 115% of APIs
± 5 % variation of standard value 4-6 kg/cm2
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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
Compression (Finished dosage form)
5 tables 5 tablets 20 tablets
NOTE: -
ACCEPTANCE CRIETERIA
Friability
NMT 1% loss of their weight ± 5 % of avg. wt
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20 tablets
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6 tablets
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20 tablets after 30 mins Film Coating
TESTING PLAN
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6 tablets
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10 tablets
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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
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
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
Process Measurement
Experimental Details Sampling Plan Performance Parameters Acceptance Criteria
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 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 Coater ID Temperature Viscosity of ○ TC 915 setting 30 C to solution ○ 45 C 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
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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