ETO Sterilization Re-qualification

ETO Sterilization Re-qualification Requirements

1. Re-qualification Frequency

• Minimum annual requirement
• At least once per year, verification data, subsequent re-validation data, and routine processing data must be reviewed
• The scope of re-qualification must be determined and documented
• The review procedure shall be documented

2. Is Re-qualification Needed if No Product Changes Occur?

• Yes, re-qualification is still required

3. Re-qualification Items

• Based on certain preconditions, the following options are available:

• Full re-qualification
• No need for physical or microbial re-validation
• Small-scale microbial performance validation

Prerequisites for Re-qualification

a) The following must be reviewed/tested:
b) Whether any significant changes affecting product sterility have occurred in:

• Product design
• Manufacturing/packaging materials
• PCD (Process Challenge Device)
• Suppliers
• Manufacturing areas/facilities
• Load configurations or manufacturing processes
  c) Bioburden trend analysis of products;
  d) Whether temperature distribution studies and sterilizer operation demonstrate significant changes since last qualification;
  e) Whether temperature distribution and recirculation checks in preconditioning chambers or aeration zones show significant changes since last qualification;
  f) Whether ETO Sterilization process history since last validation demonstrates reproducibility;
  g) Whether change control and preventive maintenance records confirm no equipment modifications affecting the process;
  h) Whether no alterations to the ETO Sterilization process affecting sterility have occurred;
  i) If ETO Sterilization process specifications changed, re-qualification must include verification of EO residue limits compliance with regulatory requirements.

Regulatory Standards

• ISO 11135:2014 (Sec. 9.2: Requalification criteria)
• FDA 21 CFR 211.113 (Sterilization process controls)
• EU GMP Annex 1:2022 (Sec. 8.5: Revalidation requirements)

ETO Sterilization Re-qualification Requirements

The re-qualification shall include a review of chamber performance and annual engineering changes to ensure the original IQ/OQ results remain valid. The review must cover:

• Preconditioning zone temperature/humidity profiles (if applicable);
• Actual empty chamber humidity profiles;
• Aeration zone temperatures (if applicable);
• Additionally, even if process specifications are met, inspections must be triggered by:
  • Adverse trends in equipment performance,
  • Sterility failures;
  • To determine if re-validation is warranted.
• Sterilization experts shall define the scope of required physical and microbial re-validation based on review outcomes.

Critical Considerations for Sterilization Re-qualification

1. Handling Significant Changes

• If major changes are identified during re-qualification, re-execution of IQ/OQ/PQ may be required:

• IQ (Installation Qualification): Verify modified equipment/software installation.
• OQ (Operational Qualification): Retest impacted functional parameters.
• PQ (Performance Qualification): Re-validate sterilization efficacy under new conditions.

2. Additional Requirements for Parametric Release

For facilities using parametric release (relying on process data rather than BI testing):
a) Re-validation frequency: Must be performed at least annually;
b) Re-validation scope: Must include microbiological studies to confirm:

Situations Requiring Full Requalification (IQ/OQ/PQ):

a) Major maintenance of the sterilizer;
b) Structural, location, or environmental changes;
c) Unexplained sterility failures;
d) Changes in EO supply/delivery, diluent, or chamber load configuration.

Exemption from Physical or Microbial Re-qualification

When the following conditions are met:

• No changes in product, packaging, equipment/services, or processes;
• Chamber performance and engineering review are qualified;
• Routine sterilization processes have operated reliably during the period;
  ? Professional judgment may determine that physical or microbial re-qualification is not required until the next review.

Limited-Scale Microbial Performance Qualification

• May be required in specific cases, such as:

• Verifying continued suitability of BIs relative to product bioburden;
• Providing evidence that no unintended changes occurred since the previous (re)qualification study after a defined time interval.
  • General requirements (at minimum):
• One short-cycle or half-cycle run;
• Including temperature and humidity measurements of sterilized items.

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