Cleaning validation

Cleaning validation is a critical function in pharmaceutical manufacturing. Regulatory agencies have placed great emphasis on demonstrating that a cleaning process prevents cross-contamination.

Cleaning validation is documented evidence that an approved cleaning procedure will reproducibly remove the previous product or cleaning agents used in the equipment below the scientifically set maximum allowable carryover level.

 

We can assist you at all steps of cleaning validation:

  • cleaning validation training
  • cleaning validation SOP development
  • toxicological assessment of APIs based on NOAEL
  • calculation of PDE
  • calculation of MACO
  • product bracketing and choose the worst case product(s)
  • calculation of acceptable residue limit (ARL) (Swab and Rinse)
  • calculate acceptance criteria for cleaning verification
  • development and validation of analytical methods for cleaning validation samples
  • perform recovery study
  • design of cleaning validation protocols
  • design of cleaning validation report
  • analysis of validation samples (direct surface samples and rinse samples)
  • filling in cleaning validation report
  • cleaning verification SOP development

 

Toxicological assessment of APIs based on No Observable Adverse Effect Level (NOAEL) is the most difficult step. NOAEL is defined as follows:

  • NOAEL must be established for all critical effects identified
  • the NOAEL is the highest tested dose at which no adverse effect is observed
  • if NOAEL is not calculable, the lowest-observed-effect level (LOEL) may be used
  • determined by toxicological expert

PDE is calculated based on NOAEL/LOAEL. After calculation of PDE Maximum Allowable Carryover (MACO) can be calculated. MACO is the mathematically calculated quantity of residue from a previous product when carried over into a different product that can represent potential harm to the patient.

To minimize sampling bracketing approach can be applied. Bracketing groups typically based on:

  • equipment
  • cleaning procedure
  • dosage Form
  • cleaning SOP

Any product that does not conform to ‘bracket’ must be validated individually.

 

Worst-case product determination is based on:

  • product toxicity
  • product solubility
  • cleanability
  • product contact area
  • batch size
  • product potency
  • release mechanism