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483s from recent FDA inspections reveal often-cited systemic deficienies | BioQuality.biz

Click the title above to see the whole post. These 483s come from recent issues of BioQuality. Please support us by signing up or subcribing today and telling your colleagues about us. See the links in the box to the right to sign up for a free membership or to subscribe.

The Quality System

Inadequate handling of OOS result for potency of drug product:

  • A retest was performed using the original sample and all results were within specification
  • The lot was then re-sampled with no justification and an additional 3 samples were tested and a range of within-specification results was obtained
  • Original OOS result invalidated without clearly assignable laboratory cause
  • Only the within specification results were reported

The responsibilities and procedures applicable to the quality control unit are not fully followed

The Quality Unit does not review or approve maintenance procedures or records

The Production System

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not written and followed, specifically:

  • Vent Filter Integrity Testing is not performed for any of carboy vent filters, and Drug products inside the carboys are considered sterilized material
  • There is no risk assessment that describes the impact of this practice
  • There is lack of written and approved scientific rationale for not integrity testing these vent filters
  • There are no, documents, protocols, studies, validation, and/or qualification records that address the reason why vent filter integrity testing is not performed

Firm demonstrates poor aseptic practices during the filling of sterile products including, but not limited to:

  • An operator performing critical aseptic operations with exposed skin at the forehead, posing an unreasonable risk of the product becoming contaminated
  • Operators moving very quickly in the aseptic area, which may create unacceptable turbulence in the area, and disrupt the unidirectional airflow
  • Operators leaning halfway in and out of the class 100 area while performing interventions over opened bottles

The Facilities and Equipment System

Equipment used in the manufacture, processing, packing or holding of drug products is no of appropriate design and suitably located to facilitate operations for its intended use and cleaning and maintenance

  • Specifically, a number of design and/or structural defects related to equipment or the locatio of equipment in the facility were noted through the course of the inspection including:
    • the fill room for aseptic filling line [redacted by FDA] contains a “U” shaped conveyor belt that makes it necessary for operators to enter the curtained class [redacted by FDA] area of the fill room from the ISO Class [redacted by FDA] area of the fill room by ducking beneath a conveyor belt that is no more than 4 ft high in order to make and/or inspect connections between the surge bottle and the filling machine
    • Monitoring of connections between surge bottle and filling machine is otherwise impaired by a plastic curtain and the distance between the exterior of the conveyor system and the connections

Equipment cleaning validation did not include cleaning agent residue testing

Clean-in-place validation did not include the worst case

Disinfectants used in aseptic processing area and surrounding clean rooms were not rotated

The Laboratory Controls System

Sampling system and method are not appropriate and adequate

  • Firm cannot guarantee that representative samples were collected and appropriately delivered for testing to the microbiology and chemistry laboratories
  • Current sample identification system is inadequate
  • The approach for collecting samples for particulate matter testing independent of the batch size is not scientifically sound
  • There is no written, approved standard operating procedure that describes thoroughly the sorting of samples in the manufacturing area prior to sending them to the respective
  • As a result, the results obtained on each test for finished products may be questionable in that they may not reflect a truly-representative sampling and testing of the filled product
  • In addition, Managers, Supervisors, and other top officials of the Microbiology and other departments could not provide the scientific and statistical rationale behind current sampling practices

The Materials System

Firm failed to reject a lot of components which failed to meet appropriate written specifications, specifically:

  • Lots of Sodium Taurodeoxycholate (TDOC), used to disrupt influenza virus to make a split virion vaccine, were delivered in 2010
  • 15 lots failed the ID test performed, but the lots were accepted for use
  • An investigation was not initiated to determine the reason for identification failures and the vendor was never contacted to inquire about the possible changes to TDOC lots
  • Without further investigation into possible changes to TDOC, the [redacted by FDA] of the lots failing identification were included into the [redacted by FDA] of acceptable [redacted by FDA]

The Packaging and Labeling System

Some labeling on final product packaging was found to be discrepant with labeling on the outer box containing multiple final packages:

  • Specifically, the expiration dates differed by two years

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