QUALIFICATION AND VALIDATION OF FLUID BED EQUIPMENT WITH BOTTOM SPRAY TECHNOLOGY

MASTER OF PHARMACY DISSERTATION PROTOCOL SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA

BY MANEESH MADHUKAR NARKAR Under The Guidance of Mr. KRISHNANANDA KAMATH K., M.PHARM.

P.G. DEPARTMENT OF QUALITY ASSURANCE, SRINIVAS COLLEGE OF PHARMACY, MANGALORE 574143 2012 2013

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA ANNEXURE REGISTRATION OF SUBJECT FOR DISSERTATION

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NAME OF THE CANDIDATE ADDRESS

MANEESH MADHUKAR NARKAR. DEPT. OF QUALITY ASSURANCE, SRINIVAS COLLEGE OF PHARMACY, VALACHIL, POST FARENGIPETE, MANGALORE - 574143

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NAME OF THE INSTITUTION

SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE.

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COURSE OF STUDY & SUBJECT

MASTER OF PHARMACY (QUALITY ASSURANCE)

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DATE OF ADMISSION

26/05/2012

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TITLE OF THE TOPIC: QUALIFICATION AND VALIDATION OF FLUID BED EQUIPMENT WITH BOTTOM SPRAY TECHNOLOGY

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BRIEF RESUME OF THE INTENDED WORK : NEED FOR THE STUDY: Equipment qualifications are always performed to confirm functionality of the equipment as per defined specifications, both prior to and after installation. However, documented records of equipment qualification and validation have sometimes not been given sufficient consideration. As a consequence, companies have not always been able to provide documented evidence to inspectors reflecting the time and effort spent in carrying out these activities. Quality Assurance function have critical role in overseeing and coordinating qualification and validation activities. The qualification and validation approach has been discussed due to its real importance within a productive process in relation to the products quality attributes, like purity, safety and effectiveness. Process validation is establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics. So, the validation consists of a series of qualifications that involves tests, systems verifications and also critical process parameters that are its regulating keys, and can vary within an acceptance limit. The process for equipment qualification follows the 4Qs model for the specification, installation check, and monitoring of ongoing equipment performance. Design Qualification (DQ): Define the functional and operational specifications of the equipment, any associated software and ancillary system for the intended purpose. To be performed before purchase of a new equipment. Installation Qualification (IQ): Establish that equipment is delivered as designed and specified and that it is properly installed in the selected environment. Operational Qualification (OQ): Document that the equipment will function according to its operational specification in the selected environment. Performance Qualification (PQ): Document that the equipment consistently performs according to specification and intended use.

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EQUIPMENT DESCRIPTION: The Fluidised Bed Equipment, FBE is used for:Rapid and efficient drying of wet granulation mass, granulation of powders andCoating of Pellets. The material to be processed is loaded into the bowl of the FBE. The bowl has a fine SS mesh at the bottom. The air used for drying/fluidizing is successively filtered through Pre (EU 4- filter grade, 10 micron rating, 95% efficiency), Fine (EU 7 grade, 3 micron rating, 99% efficiency) and finally through HEPA filters (EU 13 grade, 0.3 micron rating, 99.997% efficiency). Hot, filtered air up to 90 Cel. is passed at high velocity from the bottom of the FBE bowl through the process material. Because of the high velocity of the air the process material is fluidised. The fluidising air results into a very efficient heat and mass transfers (heating, cooling, drying, granulating, coating). The machine can be divided in following sub sections: Inlet Air Handling Unit Machine Tower (Lower Plenum, Product Container, Expansion Chamber & Product Filter Housing) Spraying System Exhaust Air Handling Unit Wet Scrubber Control Panel
o

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BRIEF PATHWAY OF THE INTENDED WORK : OBJECTIVE OF STUDY : The objective of this work is to qualify Fluid Bed Equipment,

according to the specified requisites and validate the Process. 7.2 REVIEW OF LITERATURE: A literature survey was carried out for the work done on qualification of Fluid Bed Equipment. Few methods have been reported and the collections of reference are reproduced below.

Dr.Mukesh Gohel and Dr. Rajesh Parikh1 has elaborated history and chronological developments in fluid bed systems. Various concepts of fluidization, parameters to be controlled during fluidization, various classification of fluid bed system. They have elaborated various advantages, disadvantages and applications of fluid bed system. Lipsanen, T., 2 has described Process Analytical Technology Approach on fluid bed granulation and drying Identifying Critical relationship and constructing the design space. The approach in this thesis was to identify the source of variation that are mainly related to moisture. The aim was to determine correlations and relationships, and utilize the PAT and design space concepts for fluid bed granulation and drying. Physical in-line measurements (i.e. temperature , air flow rate)and various particle size determinations were used to increase process understanding.

Samira El Mafadi, Murielle Hayert, Denis Poncelet3 in their scientific paper described about fluidization control in wurster coating process. The particulate coating process in FBE involves different sub process involves particle wetting, spreading also drying of coating applied. These subprocesses are done simultaneously to particle fluidization. All parameters are known to affect coating quality; due to this particle motion in Wurster needs to be observed carefully. These observations have achieved to understand general phenomenon which takes place inside the bed and allowed to develop easy methods for optimizing all parameters affecting this process. Pam-Glatt FBE Manual 4 describes about safety precautions, technical description about AHU ,fan. Description about machine orientation, various components like machine tower, filter unit ,sealing unit of filter and product container, inlet AHU, exhaust air handling unit, spraying system. It describes PLC unit and various interlocks , password protection facilities. It also covers commissioning, maintenance data.

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Source of Data: References from library Srinivas college of pharmacy www.pharmainfo.net www.google.com Journals and Publications

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Methodology:Qualification and validation of fluid bed equipment with bottom spray technology shall be carried out at Indoco Remedies Ltd., Goa. As part of validation requirements, documentation and information file will be established. It will include a full description of the equipment, specifying its acceptable criteria. Fluid Bed Equipment : Make : Pam Glatt will be used for project work.

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Does the study require any investigations or interventions to be conducted On patients or other human or animals? If so please describe briefly: -- Not applicable

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Has the Ethical Clearance been obtained from your Institution in case of 7.3? -- Not applicable LIST OF REFERENCES:

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http://onlinelibrary.wiley.com/doi/10.1002/jps.3030480808/abstract Journal of the American Pharmaceutical Association, Aug.1959 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799576 Predicting Particle Size During Fluid Bed Granulation Using Processor Pharmaceutical process validation by Robrt A.Nash and Alfred H. Wachter. Fluid Bed Equipment manual supplied by Pam- Glatt.

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SIGNATURE OF THE CANDIDATE REMARKS OF THE GUIDE

Maneesh Madhukar Narkar. Forwarded for Approval Mr.Krishnananda Kamath K.,

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NAME AND DESIGNATION OF GUIDE

Assistant Professor, Dept of Quality Assurance

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SIGNATURE Dr. E.V.S. Subramanyam,

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HEAD OF THE DEPARTMENT

Professor and Head, Dept of Quality Assurance

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SIGNATURE

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REMARKS OF THE PRINCIPAL

Forwarded for approval

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SIGNATURE

Dr. Ramakrishna Sharbaraya A. Principal, Srinivas college of pharmacy, Valachil, Mangalore.