Performance Qualification of a vial washer

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Performance Qualification of a vial washer
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Contents

• Introduction-DQ, IQ, OQ, PQ
• Performance Qualification of a vial washer

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Introduction

• DQ(Design Qualification)
• IQ(Install Qualification)
• OQ(Operation Qualification)
• PQ(Performance Qualification)

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Performance Qualification of a vial washer

• The importance of PQ for a vial washer
• Performance of the vial washer should be
  qualified. Although depyrogenation may be
  achieved using a heating tunnel or oven, if the
  washing process cannot remove chemical
  contaminants or particles, they will produce a
  pyretic response in humans or animals, although
  there are no pyrogens present.

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Performance Qualification of a vial washer

• The importance of PQ for a vial washer
• Some drug manufacturers may perform a
  qualitative trace study for coloring matter in
  washed vials using a white wiper to verify the
  performance of the washer, but it is not a
  quantitative method to reflect the actual
  performance of the washer for particles,endotoxin,
  and chemical contaminants.

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Performance Qualification of a vial washer

• Provision
• -21CFR Part 211.94
• Drug product containers and closures shall be
  clean and, where indicated by the nature of the
  drug, sterilized and processed to remove
  pyrogenic properties to assure that they are
  suitable for their intended use.

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Performance Qualification of a vial washer

• Provision
• -The FDA Guideline for Dosage Form
  
• Drug Manufacturers
• Determine how containers and closures are
  handled and stored.
• Decide if the cleaning, sterilization, and
  depyrogenization are adequate, and have been
  validated.

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Performance Qualification of a vial washer

• A brief description of our vial washer (LIBRA
  HYDRA1000-7-B)
• Our automatic vial washers (LIBRA
  HYDRA1000-7-B) are designed to wash externally
  and internally many kinds of glass or plastic
  cylindrical containers.
• There are eight washing stations, plus two
  dripping stations equipped with independent
  connections to their respective circuits to
  prevent cross- contamination among the various
  media.

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Performance Qualification of a vial washer

• A brief description of our vial washer (LIBRA
  HYDRA1000-7-B)
• Each station has seven washing channels.
• When washing, the needles on each station
  enter the vials as the various media are sprayed.
  
• Each washing channel may have a different
  spray strength due to the distance of the spray
  nozzle from the utility supply point.
• Media spray time can be individually adjusted
  according to bottle size and production speed.

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Performance Qualification of a vial washer

• Designing of PQ Study
• Parameters which will affect the ability of
  the cleaning
• The ability of cleaning is largely dependent
  on vial size, media spray time, and pressure and
  washing speed.
• So each size of the vials will be subjected
  to the PQ study.
• To incorporate the worst case scenario into
  the validation studies, higher washing speed
  (10), shorter media spray time (-10), and
  lower media spray pressure (-10) than the
  pre-established washing cycle will be implemented
  during validation.

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Performance Qualification of a vial washer

• Designing of PQ Study
• whats the purpose of washing?
• The vial washer is used to clean the drug
  container to eliminate the contamination
  (endotoxin, chemical substance, particles etc.)
  from the container itself to ensure that the
  products produced meet expectations for purity,
  identity, safety, and quality.
• Thus decontamination studies for endotoxin,
  chemical contaminants, and particles should be
  performed.

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Performance Qualification of a vial washer

• Designing of PQ Study
• whats the purpose of washing?
• As the internal surface of the vial is
  product-direct contact, a certain quantity of
  each contaminant will be placed into the vials,
  and washed in the vial washer.
• Then the quantity of contaminants in each
  washed vial will be determined, thus the
  reduction of contaminants can be obtained to
  verify the machine performance.

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Performance Qualification of a vial washer

• Questions regarding with the contamination level
  before washing and the acceptance level after
  washing
• The initial contamination level was obtained by
  testing samples taken from three different
  production lots according to Military Standard
  105E.
• In this case, for endotoxin, the initial level
  is quite low, and the depyrogenation process of
  dry heat will ensure the endotoxin reduction, so
  we use 1000-10,000EU as the initial level, and
  set acceptance criteria at three log reduction of
  1000EU.

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Performance Qualification of a vial washer

• For particle and chemical substance (free
  alkali), we double the data averaged from the
  test results of the initial contamination level
  testing.
• As any particle or chemical contaminants may
  affect the quality of the products, the
  acceptance criteria should be free of particles
  and chemicals for washed vials.
• Thus three decontamination studies were
  performed for each kind of vials.

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Performance Qualification of a vial washer

• Each study was challenged three times to
  verify the reproducibility of the machines
  performance.
• Preparation procedures of contaminated testing
  vials for each study and their acceptance
  criteria are listed in Figure 1.

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Performance Qualification of a vial washer

• For each study, the quantity of vials to be
  washed is the same as normal production size to
  demonstrate the performance of the normal
  process.
• Those 280 contaminated vials were divided into
  four groups.
• The first group is put at the beginning of the
  washing process, the second and third group is
  put in middle of the process randomly, while the
  fourth group is scheduled at the end of the
  washing process.

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Performance Qualification of a vial washer

• Each group contained 70 vials in 10 rows, each
  row containing seven contaminated vials washed on
  each washing channel.
• To ensure each washing channel will be
  challenged and easy to analyze in the case of
  failure, these contaminated testing vials were
  marked consecutively, and deliberately arranged
  as specified in Figure 2.

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Performance Qualification of a vial washer

• The washed vials were carefully collected with
  gloves, tweezers, placed into identified,
  particle-free cleaning bags as they exited the
  washer, and sent to the laboratory for testing.
• As outside contamination will significantly
  affect the test results, special attention was
  required during the collection of the vials.

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Performance Qualification of a vial washer

• Laboratory test results for the washed vials
  demonstrated the high efficiency of the machine.
• Testing vials for particle decontamination
  study were all free of particles and testing
  vials for the chemical decontamination study are
  all free of sodium chloride.
• Three log endotoxin reductions were achieved
  for each endotoxin decontamination study.
• Further analysis of the results for residual
  endotoxin demonstrated the performance of the
  vial washer.
• The average testing results for vials washed
  at different locations show an obvious trend as
  illustrated in Figure 3.

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Performance Qualification of a vial washer

• It appears to be nearly a 400 variation in
  performance between Channel number one and
  Channel number seven.
• This is due to the distance of the spray
  nozzle from the utilities supply point.
• The closer channel has the higher washing
  efficiency due to the high pressure of media when
  sprayed out.
• There is a consideration to add a utility
  supply point at the other side of each washing
  station to increase the pressure of sprayed media
  at locations five, six, and seven to ensure a
  more uniform performance.

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Performance Qualification of a vial washer

• Conclusion
• The PQ testing of the washer is essential to
  ensure the elimination of contamination from the
  vials itself.
• The quantitative decontamination study can
  provide a high degree of assurance to validate
  the performance of the washer with presetting
  parameters.
• Requalification of the washer is not necessary
  if no change occurs.
• Of course, in case of any changes on the vials
  or washing parameters, the washing cycles applied
  should undergo PQ testing again.

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Performance Qualification of a vial washer

• Conclusion(continue)
• Periodic initial contamination testing for
  supplied vials is recommended to ensure all vials
  to be washed are still under validated
  conditions.
• Periodic testing of washed vials especially
  coming off Channel number five to seven is also
  advisable.