VALIDATION

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VALIDATION PERSONNEL

• GUIDED BY
• DR.N.P. CHOTAI
• PREPARED PRESENTED BY
• VISHAL B,NAKRANI
• M.PHARM(Q.A.,2nd SEM.)
• ID.NO05PH912
• DATE31/05/06

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• Content
• Validation definition
• Advantage of validation
• Protocol development
• GMP Inspectors check list for validation
• Personnel
• Validation Working Groups
• Reference

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Validation

• WHO validation definition
• The documented act of proving that any
  procedure, process, equipment, material,
  activity or system actually leads to the
  expected results.

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• The WHO GMP Guidelines state
• Validation studies are an essential part of good
  manufacturing practice and should be conducted in
  accordance with predefined protocols.
• written report
• process and procedures
• processing
• testing
• cleaning procedures

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• Functionality, consistency and
• repeatability
• is confirmed by
• validation

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• Validation as such
• does not improve the process
• but it
• confirms and assures that the process
• Has been well developed
• It is well maintained
• It operates as it should

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• Advantages of validation
• During the process the knowledge of process
  increases
• Assures the repeatability of the process
• Assures the fluency of production
• Assures that the product is continuously produce
  according to the marketing authorisation

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• Decreases the risk of the manufacturing problems
• Decreases the expenses caused by the failures in
  production
• Decreases the risks of failing in GMP
• Decreases the expenses of the every day
  production even though the validation itself will
  create expenses

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• Protocol development
• Each stage in the validation of the overall
  process should proceed in accordance with a
  pre-established and formally approved detailed,
  written protocol, or series of related protocols.
  
• Protocols should have a Title, Date and a unique
  Identification or Reference Number. They should
  be formally authorized/approved by persons with
  the competence and authority to do so.

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It should specify the objectives and scope of the
study. Like, a clear and precise definition of
the process, equipment, system or sub-system
which is to be the subject of the study, with
details of performance characteristics.
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• GMP Inspectors check list for validation (1)
• Check that the manufacturer has
• A VMP and multi-functional team for validation
• Planned approach , defined requirements
• Identified and described processes
• Analyse the amount of validation work to perform

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• GMP Inspectors check list for validation (2)
• Check that the manufacturer has
• Selected methods and tools for validation
• Created protocols
• Performed DQ, IQ, OQ, PQ and documented results
• Exerted change control, set revalidation time

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• Validation - Logical entity
• protocol
• procedure
• report

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• Personnel
• Personnel actually performing any validation
  studies, and in routine operation can have so
  crucial an effect on the quality of the
  end-product, it is appropriate and necessary to
  consider both these aspects of personnel involveme
  nt.
• Appropriately qualified personnel should ensure
  that the protocol and the testing methodology are
  properly evaluated and certified.

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• All personnel conducting tests should be trained
  and experienced in the use of the instruments,
  measuring devices and materials used.
• Engineering/maintenance personnel should be fully
  trained and competent in the operation and
  maintenance of the machines, equipment, and air
  control systems involved.
• Any operators involved in performing a
  validation study should adopt the same
  techniques, disciplines, and standards of
  hygiene, clothing and behavior as in normal
  routine manufacture.

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• It is therefore vital that all personnel involved
  in validation are trained, and fully understand,
  the concepts and principles of GMP, and
  validation.
• They must understand the importance of personal
  hygiene and cleanliness, and be made fully aware
  of the possible hazardous consequences of product
  contamination.
• Operators should be provided with suitable Clean
  Room clothing and trained in appropriate gowning
  technique.

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• The type of clothing to be worn, and gowning
  process should be defined in written procedures,
  available to the operators, and preferably
  displayed in the changing room.
• The same clothing/gowning standards should be
  observed during validation studies as in routine
  production, and vice versa.

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• Validation Working Groups
• The executive part of the validation work should
  be delegated to dedicated personnel
• Director of validation
• Manager or senior manager of validation
• A representative from quality assurance
• A representative from technical services
• A representative from research development
• A representative from quality control
• A representative from production

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• Director of validation
• Primary responsibility
• Directs company-wide process validation
  program.
• Directs company-wide cleaning validation
  program.
• Reviews and/or approves Master Batch
  Records for development and Production, as
  required.
• support company-wide equipment
  qualification and validation program.

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Supports company-wide computer system
validation program. Supports company-wide
activities associated with development of new
technology, improvement of existing technology
and utilizing newer, more automated equipment
and processes. Supports company management in
evaluation of new products, technology and
equipment.
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• Essential functions
• Designs, implements and oversees company-wide
  programs for process and cleaning validation.
• Ensures that the system is in compliance with
  federal and industry guidelines, and that each
  system is documented and tracked in an orderly
  manner.
• Designs, implements and oversees studies aimed to
  determine whether process or systems meet or
  exceed the specifications of its design, is
  suitable for its intended application, conforms
  to cGMP requirements, satisfies concerns of
  regulatory agencies and meets company goals
  established for quality.

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• Reviews and gives final approval for written
  validation protocols and summaries.
• Reviews and approves validation section of change
  control notices to ensure that each process
  continues to operate within its designed
  parameters.
• Reviews and approves procedures that have been
  established to revalidate the process in the
  event of a process or equipment change.

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• Ensures validation protocols and studies are
  properly documented, archived and stored for
  timely retrieval.
• Discusses validation studies and plans with
  customers and regulatory agencies as required
  during reviews or inspections.
• Develop and submit quarterly and monthly reports
  as defined by Manager
• Responsible for Master Validation Plans, SOPs,
  and Validation Guidelines. Reviews and approves
  SOPs in their related area.
• Reviews and approves Master Batch Records.

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• Oversees and approves all documents pertaining to
  companys quality development program, such as
  process development protocols and technology
  assessment summaries.
• Designs and evaluates all documents associated
  with development and implementation of new
  technology and improvement of existing
  technologies, such as master batch records,
  evaluation protocols, summary reports and change
  control notices.
• Participates in other activities, as may be
  requested, relative to new products and/or new
  technology transfers.

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• Performs employees performance reviews and
  submits them for approval in a timely fashion.
• Takes any corrective actions required up to and
  including termination as appropriate and in
  accordance with company policies and procedures.
• Builds and maintains a staff of professional,
  highly motivated and knowledgeable individuals.
• Participates in selection of personnel and
  provides effective training.
• Establishes standards of performance in
  accordance with company guidelines and evaluates
  performance against those standards for all staff
  members.

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• Knowledge/Skills/Abilities
• Thorough knowledge and understanding of
  governmental requirements and industry standards,
  related to current Good Manufacturing Practices
  and other appropriate government regulations and
  requirements as related to essential job
  functions
• Thorough knowledge of current validation
  compliance, standards, requirements for a
  Pharmaceutical Industry, both domestic (FDA) and
  international (ICH).
• Ability to establish validation standards, SOPs
  and audits meeting current and future FDA
  requirements
• Experience working with and/or leading
  cross-functional groups

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• Excellent written, verbal and interpersonal
  communication skills, highly organized and
  detail-oriented.
• Ability to effectively and directly interface
  with FDA and technical company personnel at
  various levels
• Ability to effectively communicate, directing,
  guiding personnel who are not direct reports.
• A strong scientific experience and knowledge of
  analytical, research, engineering, manufacturing,
  quality control and quality assurance.

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• Good computer skills with knowledge of Microsoft
  Office programs (Word, Excel, Power point )
• Ability to utilize statistical techniques and
  approaches to reach scientifically sound
  decisions regarding validation issues
• Thorough knowledge and understanding of product
  formulations, pharmaceutical technology and
  equipment performance relative to solid dosage
  forms, liquids and semi-solids.

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• Education/Experience
• B.S., M.S. or PhD in Industrial Pharmacy,
  Pharmaceutics, Chemical Engineering or related
  science area

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• Manager/Senior Manager, Validation
• Responsibilities
• Responsible for the management of the Validation
  Department personnel
• Responsible for Validation Department budget
  development and monitoring
• Lead and coordinate the qualification and
  validation efforts for new GMP facilities

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• Ensure that appropriate validation master plans
  addressing facilities, utilities, equipment,
  cleaning, and process are established and
  implemented according to timelines
• Manage and coordinate the activities of
  contractors performing qualification and
  validation work
• Ensure that a validation/re-validation program is
  established and implemented in the new
  manufacturing facility and provide program
  oversight

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• Review, approve, source and/or write validation
  documents
• Provide technical expertise and interpretation on
  regulations and guidelines as they relate to
  validation activities
• Oversee the development and revision of
  validation procedures and protocols to ensure
  that regulatory compliance and company objectives
  are maintained
• Ensure that the Validation Department personnel
  are appropriately coached, trained and developed
  for current and anticipated projects
• Prepare and assist with the inspections from
  regulatory agencies

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• Requirements
• Bachelors degree in Engineering, Science or
  related technological field or equivalent
  combination of education and experience
• Seven to ten years experience of validation
  experience in a cGMP environment with increasing
  levels of responsibility for a wide range of
  validation projects
• Thorough knowledge of validation principles,
  manufacturing processes, quality systems,
  engineering design fundamentals, regulatory
  agency expectations and industrial trends
• In-depth knowledge of validation requirements
  (GMP, FDA, etc.) for pharmaceutical manufacturing
  facilities, equipment and systems

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• Proven track record in managing a validation
  department with multiple direct reports
• Demonstrated ability in effectively managing
  multiple validation projects simultaneously
• Excellent leadership and organization skills to
  effectively directing and managing validation
  personnel and contractors in ensuring project
  completion on time
• Excellent verbal and written communication skills
  including the ability to write, revise, and
  comment on validation protocols and reports

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SPECIFIC RESPONSIBITIES OF EACH PERSONNEL WITH THE SCOPE OF VALIDATION
Engineering Install qualify certify plant, facilities equipment support system.
Research development Design and optimize manufacturing process within design limits specification /or requirements in other words , the establishment of process capability information
Production Operate maintain plant, facilities, equipment support system the specify manufacturing process within its design limits, specification/or requirements
Quality-assurance Establish approach validation protocol conduct process validation by monitoring, sampling, testing, challenging, /or auditing the specific manufacturing process for compliance with design limits, specification, /or requirements
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• Reference
• 1.mednet3.who.int/prequal/pq_pres/
  workshop_Russia/M08-Validation02-f_U.ppt
• 2.siop.org/_Principles/principlesdefault.htm -
  16k
• 3. www.genitope.com/text/G7605.htm - 8k
• 4. Pharmabiz, Sunday, april09, 2006
• 5.Validation standard operating procedure

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THANK YOU