Sterilization process validation

The objective of the sterilization process validation is to determine that the manufacturer’s current sterilization process can consistently achieve sterility and does not cause any undesirable effect on the product or its packaging.

Elements of the validation process

There are some common elements in any sterilization process validation which should be adequately addressed, these include:

1. Sterilization cycle development
2. Biological and physical measurement controls
3. Empty chamber studies
4. Loaded chamber studies
5. Routine use or ongoing monitoring
6. Validation maintenance and change control

Validating the sterilization process is part of the production and process control system to ensure the products are manufactured to meet predetermined specifications. For sterilization processes, the primary specification is achieving the desired Sterility Assurance Level (SAL). Other specifications may include sterilant residues and endotoxin levels.

The sterility of a product is defined by the probability of identifying viable pathogens on the product after the sterilization process has been completed. This is expressed as SAL, and historically an SAL of 10^-3 or 10^-6 was used. An SAL of 10^-6 means a probability of 1 in 1,000,000 chance of finding a non-sterile unit after terminal sterilization.

Specifying the validation protocol

The validation protocol objective is to specify the procedure and tests to be conducted during the validation process and to determine which data to be collected. In general, a validation protocol will have the following element:

1. Identification of the product (i.e., the medical device)
2. Purpose and objective
3. Equipment to be used
4. Tests to be performed
5. The test methods
6. Acceptance criteria of the method
7. Approvals

Sterilization methods

There are several options for sterilization that a pharmaceutical company can use. Common methods include sterilization by ethylene oxide (EtO), radiation, or steam.

The general outline of these validation processes is as follows:

1. Ethylene oxide validation:
   1. Equipment IQ/OQ/PQ (installation Qualification, Operational Qualification and Performance Qualification)
   2. Fractional cycles with products and biological indicators
   3. Half and full cycles with biological indicators
   4. Validation support testing
2. Radiation validation
   1. Dose mapping study
   2. Determination of product bioburden (bioburden test method validation)
   3. Verification dose resistance experiment
3. Steam validation
   1. Equipment IQ/OQ/PQ
   2. Temperature profiles of the product during sterilization cycles
   3. Fractional cycles with the product and biological indicators
   4. Half cycles with the product and biological indicators
   5. Sterility testing of product and biological indicators

At Synergy Bioscience, we provide complete consulting solutions to support your sterilization process validation. Our consultants and technicians are seasoned professionals who are fully trained to ensure you are compliant with the current regulatory requirements.