Sterile facility of a pharmaceutical industry is a sophisticated facility, where have a lot of requirements to maintain the facility. So when a sterile product failure is need to be investigated, it should be with proper knowledge.


Investigation considerations

  • Comprehensive review of the BMR including deviations contained therein, of sterilisation parameter records of components and of the product lot (if applicable), accountability of number filled vs number sterilised (for terminal sterilisation), results of the bioburden monitoring of the compounding solution, filter integrity test data, preparation records of disinfectants etc.
  • Review of Media Fill results at least of the last 2 years, if applicable.
  • Review of all available results of environmental control, including personnel monitoring and water, in the production environment, covering data of at least 3 months before the event and all data generated subsequent to the event until present, taking into account the contaminants’ trend. Test data of disinfectant solutions, if appropriate.
  • Results of in-process controls of the production/manufacturing area (e.g. particle counts, differential pressures).
  • Results of container integrity tests or similar controls, where applicable.
  • Review of training records.
  • Review of validation documentation.
  • Review of any recent changes that may have been made to the process.

Reasons behind the failure

  • Faulty or incomplete sterilisation cycles (temperature drops, cycle length, abortion of cycles etc.)
  • Faulty filtration processes (filter integrity did not comply, leakage of filter housing etc.)
  • Faulty lyophilisation cycles (breakage of vacuum, insufficient decontamination of lyophiliser etc.)
  • Increased bioburden results of the compounding solution before sterilisation.
  • Critical identification results of bioburden of the compounding solution before sterilisation (e.g. occurrence of spore formers in the case of terminally sterilised products).
  • Transgression of holding times of solutions and equipment.
  • Occurrence of risky, non-validated manipulations in the filling line (e.g. mechanics interventions, long stoppages etc.).
  • Inadequate training.
  • Faulty and/or unacceptable behaviour of personnel involved in manufacturing.
  • Faulty air handling systems (fan out of service, overpressure drop affecting critical areas).
  • Environmental monitoring action conditions affecting critical areas.
  • Failed Media Fill trials, with Failure Investigation pending or inconclusive.
  • Failed validation/revalidation studies, with Failure Investigation pending or inconclusive.
  • Failed cleaning operations.
  • Inadequate sampling procedure and transfer to the laboratory.

We hope this article will be helpful for identifying the root cause of sterile product failure and also help to take necessary measures.