A seminar On Validation Of Ampoule Filling

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A seminar On Validation Of Ampoule Filling
Sealing Machine

• Department Of Quality Assurance
• Maliba Pharmacy College

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Introduction

• Validation may be defined as,
• The documented act of demonstrating that any
  procedure, process, and activity will
  consistently lead to the expected results which
  includes the qualification of systems and
  equipment

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Continued.

• The equipment validation process generally covers
  following steps..
• User Requirement Specification (URS)
• Preparation of Design Qualification (DQ)
• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)

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Stages of Qualification
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• The previous figure depicts the most commonly
  used approach to the qualification process as
  used in the pharmaceutical industry
• It shows a pyramid, which is the best way in
  which to plan a qualification/validation project
• Investing more time in the first phases will save
  time and money in later and critical phases

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Who should do Equipment Validation?

• The vendor or the user ?
• User has the ultimate responsibility for the
  accuracy of
• the analysis results and also for equipment
  qualification
• DQ should always be done by the user
• While IQ for a small and low cost instrument is
  usually done
• by the user, IQ for large, complex and high
  cost instruments
• should be done by the vendor
• OQ can be done by either the user or the vendor
• PQ should always be done by the user because it
  is very
• application specific, and the vendor may not
  be familiar with
• these
• PQ should be done on a daily basis

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Validation of Ampoule Filling Sealing Machine
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Validation Protocol

• The entire process of equipment validation is
  designed in the form of certain documented
  formats or protocols
• This helps in systematizing the study of
  equipment validation
• A validation protocol prepared by engineer or
  validation specialist
• The protocol sections contain required procedures
  and forms

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Continued.

• The procedure describe how the system is to be
  validated, while the forms document these
  procedure and provide a written record of the
  performed qualification and validation processes
• Each protocol package is divided into three
  section
• Installation qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)

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User Requirement Specification

• The user of the equipment has certain
  requirement about the equipment which he wants
  to use
• Some of the general requirements may be stated in
  the form of certain parameters like
• Size of equipment
• Speed of equipment
• Availability of spares, change part, immediate
  service at reasonable cost

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Continued.

• Low sound generation
• Lesser breakdowns
• Materials of construction
• Auto control system
• This requirements are generally discussed with
  the suppliers and based on this discussion the
  selection of the equipment is done

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Continued.

• For example,
• In ampoule filling machine, a delivery tube
  provided for repetitively forcing a measured
  volume of liquid through the orifice of delivery
  tube designed to enter the constricted opening of
  container
• The size of delivery tube depend on ..
• the opening of container
• the viscosity density of liquid
• speed of delivery desired

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Preparation of D.Q. and its Certification

• If we are going to purchase an standard equipment
  then the preparation of D.Q. dose not become very
  important because we are accepting the
  manufacturer's design as it is
• However, if a particular equipment is to be
  fabricated as per our requirements then the
  detailed D.Q. document become very important and
  essential

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Continued.

• It is advisable to work out the detailed
  equipment specifications by sitting together with
  the equipment manufacturer
• It may also be advisable to perform Factory
  Acceptance Test (FAT) at the manufacturers
  premises before dispatch of the equipment to the
  purchaser

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Installation Qualification

• Installation qualification establishes that the
  instrument is received as designed and specified,
  that it is properly installed in the selected
  environment, and that this environment is
  suitable for the operation and use of the
  instrument

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Continued.

• The qualification involves,
• Verification of approved purchase order
• Verification of invoice
• Check manufacturer and supplier
• Verification of model number and serial number
• Checking for any physical damage
• Confirm location and installation requirements as
  per recommendation of manufacturers
• Verify that the utilities required are available
• Installation shall be conducted as per
  instructions provided in the manual

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Continued.

• Ensure all relevant documentation is received
  like,
• User manual
• Maintenance manual
• List of change parts
• Electrical drawings

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Operational Qualification

• O.Q. is verification of performance of the system
  without load
• O.Q. section details the tests to be performed on
  the equipment to document that it operates
  correctly
• O.Q. involve,
• Verification of alarm control
• Perform calibration requirements identified in
  the manual or established by the validation team
• Operate the equipment at low, medium, and high
  speed as per operations manual to verify the
  operating control
• Verify that all switches and push buttons are
  functioning properly
• Establish procedures (SOP) for operation,
  maintenance, and calibration
• Establish training program for relevant staff

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Performance Qualification

• P.Q. is verification of performance of system
  with load
• Filling studies will be run on all containers and
  fill levels
• The containers will be filled in triplicate runs
• If a placebo is used, it should have similar
  physical characteristics (viscosity, density,
  foaming) to the actual fill materials
• The study should be run at minimum, maximum and
  intermittent speeds (in terms of ampoules/minute)
  
• The filler must handle the containers without
  damage and without jams
• Accuracy and precision must meet specifications

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• P.Q. of ampoule filling and sealing machine
  involve,
• Wight variation test
• Filling volume accuracy
• Particle Contamination
• Leaker test
• Oxygen content

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• Weight variation test
• In the absence of specific criteria, weight
  variation must conform to USP
• In summary, all 10 units must be within 85.0 to
  115.0 of target content, with a RSD 6.0, or
  not more than 1 of the 30 units outside of the
  85.0 to 115.0 and no units outside of 75.0 to
  125.0, with a RSD 7.8

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Continued..

• Filling Volume Accuracy
• The filling accuracy should be within of the
  adjusted and desired filling volume in accordance
  with the machine specification.
• eg.
• Attention limit 1
• Action limit 2

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Continued.

• Particle Contamination of Ampoules during
  Filling Sealing Procedure
• Ampoules should be filled with water for
  injection and afterward be inspected on the
  contamination with particles (particle classes
  10 µm and 25 µm).
• The inspection can be performed with a particle
  counter.

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Continued.

• Leaker test
• Should capillary pore or tiny cracks be present,
  micro-organisms or other contaminants may enter
  the ampoule, or the content may leak outside.
• Leaker usually detected by submerged ampoule in a
  deeply colored dye solution (usually 0.5 to 1.0
  methylene blue).
• Limitation is that capillaries of about less than
  15 um not detected by this method.

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Continued.

• Oxygen content,
• If the filler produces a nitrogen purge, the
  headspace gas should be analyzed for oxygen
  content

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Requalification

• Requalification of systems and equipment should
  be done in accordance with a defined schedule
• The frequency of requalification may be
  determined on the basis of factors such as the
  analysis of results relating to calibration,
  verification and maintenance
• There should be requalification after changes
• The extent of requalification after the change
  should be justified based on a risk-assessment of
  the change

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References...

• R. A. Nash A. H. Wachter, Pharmaceutical
  process validation Third edition
• Leon Lachman, H. A. Lieberman J. L. Kanig, The
  Theory and Practice of Industrial Pharmacy
  Third edition, Pg. No. - 667 to 674
• Manohar A. Potdar, Pharmaceutical Quality
  Assurance, Pg. No.- 8.13, 8.14
• Syed Imtiaz Haider, Validation Standard
  Operating Procedure, Pg. No. - 304 to 307
• Syed Imtiaz Haider, Pharmaceutical Master
  Validation Plan, Pg. No. 140
• http//www.validationworld.com/

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THANK YOU.