Injectables Process Validation

Identifying and establishing the relationship between the injectable product critical quality attributes and the manufacturing critical processing parameters are keys to completing a successful injectable process validation. The final version of the U.S. FDA guidance on process validation emphasizes the evaluation of data which establishes scientific evidence throughout the process life cycle.

The three-stage life cycle approach to injectable process validation can be understood as follows.

  1. Stage 1 includes the design of the process, including the identification of process variables
  2. Stage 2 includes testing the controls put in place to address the variables. These include traditional facility, equipment, and system qualification
  3. Stage 3 is the ongoing monitoring and evaluation of the process.


Stage 1 Master planning and organization

Effective master planning systems would describe the requirements and elements of systems and how they will be implemented. The master plan should have the following elements:

  • Clear objective
  • Defined scope
  • Process plan
  • Project management elements
  • Detailed schedule
  • Risk management elements
  • Stage-gate reviews against the plan
  • Efficient and effective resolution of deviations,
  • Multidiscipline expertise


Stage 2: Parenteral Process Performance Qualification

Process qualification and validation will help to identify process variables and sources of contamination that have been missed in process design. This step is meant to demonstrate to the auditors or regulators that the process has been adequately and effectively controlled.

Aseptic quality (of parenteral or injectable product) can be defined in a series of critical quality attributes (CQAs). Process steps and conditions can be established to maintain these CQAs, and process controls put in place to mitigate risks of process variables affecting the CQAs.

In Stage 2, process qualification is where the effectiveness of these control strategies is tested. For example, temperature mapping and heat penetration studies are used to test the process of sterilization where the continuous monitoring of autoclave temperature and time are critical to ensure that all parts reach the lethal temperature for the required time for complete sterilization of vials or ampoules.

We have outlined some common steps to accomplish the objective of Stage 2:

  1. Design Qualification
  2. Factory Acceptance Testing
  3. Site Acceptance Testing
  4. Commissioning
  5. Installation Qualification
  6. Operational Qualification
  7. Performance Qualification


Stage 3: Continued Process Verification

Continued process verification allows for an ongoing evaluation of the process described above. In this stage, it provides the opportunity to identify and recognize any new variables that may appear in the process, and to allow rectification.

At Synergy Bioscience, we offer the following services to ensure your injectable process validation meets the regulatory requirements:

  1. Qualification of clean rooms and classified areas
    1. Areas involved in the parenteral manufacturing or testing process
    2. Under static and dynamic conditions
    3. HEPA filter certification
    4. Airflow visualization
  2. Qualification of critical components
    1. Including equipment and process used for the cleaning, preparation, sterilization, siliconization and depyrogenation of critical manufacturing components
  3. Validation of the sterilization process (Moist heat, dry heat, radiation and ethylene oxide)
    1. Integrity of the holding vessel
    2. Integrity and effectiveness of venting filters
    3. Temperature distribution
    4. Accuracy of temperature monitoring
  4. Lyophilization
    1. Qualification and validation of equipment, systems, and utilities needed to perform lyophilization for injectables
    2. These include the lyophilizer, transport and loading equipment and systems.
  5. Cleaning validation
  6. Terminal sterilization validation

Our consultants and engineers are fully trained and experienced in injectables process validation to ensure you are compliant with the latest regulatory standards.

To discuss how Synergy Bioscience can help you, please contact us