Process Validation: Life Cycle Approach Beats Crossing Your Fingers

Knocking on wood is not 
effective process validation

If you do something right three times, you should be able to do it that way always. If this is your approach to process validation, Hal Baseman, chief operations officer at ValSource LLC, begs to differ. Baseman shared some insights about improving process validation at the PDA/FDA Joint Regulatory Conference in Washington D.C., Sept. 12-14. 

Looking Back at Process Validation

During the early 1970s, several hospitals experienced outbreaks of E. cloacae and Erwinia contamination in LVP bottles. The apparent cause was moisture seeped into a space under the bottles’ screw cap during cooling after sterilization. At the time, quality control was pretty much just testing and monitoring. This needle-in-the-haystack scenario was less a less than adequate method for ensuring product quality and patient safety – a confirmation of process capability was needed.
Despite a critical need for a change, progress toward process validation was slow. It was around the mid 1980s when it started to materialize. The 1987 FDA Process Validation Guidance defined process validation as “establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics.”
This definition was later updated, using “scientific evidence” in place of “documented evidence.” The new definition indicates that the FDA considers validation a scientific endeavor involving a continuous process of gathering and evaluating data rather than an 11th-hour documentation exercise.

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Replication as a Means of Validation

If replicating trials validates a process, why do process failures still occur? “Because stuff happens … and that stuff is process variation,” said Baseman. “Identifying and addressing process variability is key to process control.” The outbreaks of E. cloacae and Erwinia in the 1970s illustrated how they were not adequately controlling variables. Here are some common misconceptions of process validation:
  • If something has not happened yet, it will likely not happen
  • If something has not been cited during an inspection, it must be okay
  • Just complying with regulations is enough to ensure quality

How Can You Be More Confident With Process Validation?

According to Baseman, process validation needs to be a continuous process. A good approach is to apply risk-based critical thinking and focus more on the science of manufacturing. Start gathering and evaluating scientific information as you develop your process and control strategies. This will save time and resources later during your qualification and validation efforts. You should also implement technologies that help reduce risks to product quality during manufacturing.
The FDA’s “Quality Systems Approach to Pharmaceutical CGMP Regulations” guidance states that quality should be built into the product. This challenges manufacturers to better understand the sources of variations along the supply chain in the manufacturing process, control the variations and understand the impact of detected variations on the finished product. This strategy, called the process validation life cycle, links product and process development, qualification of the manufacturing process and supports innovation and continuous improvement. 

Process Validation Life Cycle

The process validation life cycle consists of three stages:


Stage 1: Process design

During this stage, you start gathering knowledge of the process to determine its capabilities, and evaluate sources of variation. You can also start to develop process control strategies based on your understanding of risks and sources of variation.


Stage 2: Process Qualification

During this stage, confirm that your process design is capable of reproducible commercial manufacturing. You can start by evaluating your facility and equipment and have equipment operators ensure that equipment operates within the intended operating ranges. Toward the end of this stage is when you commence your process performance qualification (PPQ).

Stage 3: Continued Process Verification

In this phase, you start implementing the process control strategies you developed during stage one. Then you can start gathering data from routine production and use it to provide ongoing assurance that the process remains in a state of control. This is more than an annual product review. Instead, this action involves using a system or multiple systems to continue assuring process control. 

Process Validation Lessons Learned Over the Years

Basemen noted that improving your validation processes begins by better understanding the relationship of product quality, process risks and variation control strategies. It’s important to know the process and be vigilant in understanding variation through monitoring and continually verifying that the process is effective and under control. Above all, learn from the outcomes and always look for ways to do things better.

Baseman refers to process variation as “stuff.” What “stuff” do you tangle with and how do you maintain process control? Leave a comment below.
David Jensen is a marketing communication specialist at MasterControl. He has been writing technical, marketing and public relations content in technology, professional development, business and regulated environments for more than two decades. He has a bachelor’s degree in communications from Weber State University and a master’s degree in professional communication from Westminster College.