Process validation is a crucial element for any GMP operation. 

FDA defines process validation in the Agency’s 2011 guidance “as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.” 

That same guidance document emphasizes that process validation is important for ensuring product quality.

Not surprisingly, if FDA investigators find that a company’s process validation is lacking, this can result in 483 observations and warning letters. In a presentation at the 2021 PDA/FDA Joint Regulatory Conference, FDA Director for the Division of International Drug Quality Carmelo Rosa explained that the No. 1 warning letter citation for finished drug product manufacturers from FY2018 to FY2020 concerned process validation/process control and investigations of discrepancies.

Process Validation Inspection Findings

The following are examples of process validation issues found during FDA inspections.

In one case, during a preapproval inspection involving a sterile injectable drug considered under shortage, FDA investigators reviewed the firm’s process validation documents, notably a table containing Process Performance Qualification (PPQ) information. This table showed that four PPQ batches were conducted. But one batch required reword due to the bag ports getting crushed during sealing. The investigators discovered that batch yields were low and the firm lacked documentation for having high rejection rates.

At another firm, a contract manufacturing organization (CMO) producing thyroid tablets, investigators discovered blending issues. Here, investigators analyzed two process validation samples and found the samples lacked uniformity, including less-than-potent levels of the active ingredient. 

On November 4, 2020, a manufacturer of homeopathic products received a warning letter that identified deficiencies in production and process control procedures and failure to adequately validate both the manufacturing process and equipment.

These findings illustrate the importance of having robust process validation controls and procedures. In addition to FDA, other global regulators are concerned about process validation. In May 2021, Health Canada released a draft guidance on process validation procedures for terminal sterilization processes.

Additional Process Validation Resources

Is Your Quality System Up to Par for Your Next FDA Inspection?

Flawed Process Validation, Ineffective Quality Unit Cited in Warning Letter

Incorrect Specifications, Process Validation Issues at CMO Lead to Adverse Events, Recall

FDA Warning Letters Week Of 11/8/2020: Process Validation Failures

Did you know there were 46 process validation 483 observations for human drug GMP operations in the past ten years involving blending issues? Our Top Issues report shows this, and other process validation issues. Contact us to learn how the Redica Top Issues report can provide valuable insights for your inspection preparation.

Process Validation Top Issues
Redica Systems Enforcement Analytics | Top Issues Report – Process Validation Blending 483 Observations

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