FAQ: Clarifying Process Verification vs. Process Validation in Medtech

One of the most nebulous aspects of compliance for a medical device manufacturer is knowing whether a process should be verified or validated to ensure its conformity to regulatory requirements. High-level answers to medical manufacturers' process verification vs. process validation questions can be found in the Quality System Regulation (QSR) requirements outlined in 21 CFR Part 820, which is enforced by the U.S. Food and Drug Administration (FDA). However, many device makers have expressed concerns that the QSR does not specifically define the activities that require process validation and those that require process verification.

The answers to the following frequently asked questions provide background on the intent of the QSR and should shed light on the FDA's perspective of the verification vs. validation conundrum.

What Is Process Verification?

The FDA defines process verification as “confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.”¹

What Is Process Validation?

The FDA defines manufacturing process validation as “establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.”²

What Are the Intended Outcomes of Manufacturing Process Validation and Process Verification?

Knowing the appropriate verification vs. validation choice depends on whether you want to know the answer to the question, “Are we building the right thing?” or the question, “Are we building the thing right?”. Here's the distinction between the objectives of each:

• Purpose of process validation: Building the right thing.
• Purpose of process verification: Building the thing right.

Process verification is generally approached from a systemic level while manufacturing process validation is applicable to the product's users. In that regard, a device maker's process verification should be concerned with confirming that specifications are correctly implemented by the system. Process validation activities, on the other hand, should be aimed at meeting the needs and expectations of users/customers.

Does Process Verification Prove That a Device Works As Intended?

Process verification isn't testing to confirm that a process or medical device product actually works. It's confirming that the specifications have met predetermined parameters. Manufacturing process validation comes in to play when parameters can't be measured, which occurs frequently in medtech manufacturing (more on that later).

Process verification is used throughout the life cycle of a medical device, from design development to upscaling production. However, since the QSR stipulates that objective evidence must exist as proof that specs have been met, process verification is contingent upon quantifiable metrics that serve as key performance indicators (KPIs). In short, if KPIs are measurable, the process can be verified.

Still, few processes are measurable with 100% accuracy, even with the most stringent controls. That's why the “fully verified” clause in the QSR is a sticking point for many medical device manufacturers. It's also the reason why process validation is always prudent whenever it's a cost-effective option.

What Does “Fully Verified” Mean?

The QSR has never explicitly defined what it means for a process to be fully verified. However, the chief of the postmarket and consumer branch of the FDA's Center for Devices and Radiological Health (CDRH), Joseph Tartal, clarified its meaning and context in a recent FDA Industry Basics Workshop Series.

Tartal explained that verifiability is reliant on objective evidence and defined a fully verified process as one that is “able to confirm with high confidence all of the key quality attributes.”³

“By objective evidence, we mean supporting the existence or truthfulness of it,” he said. “Objective evidence may be an observation, a measurement or a test.”

However, when objective evidence cannot be measured in a process, it cannot be fully verified and QSR guidelines call for a validation approach. The guidelines for a medical device validation approach are set forth in Section 75(a) of Part 820 which says, “Where the results of a process cannot be fully verified by subsequent inspection and test, the processes shall be validated with a high degree of assurance and approved according to established procedures.”⁴

What If a Manufacturing Process That Requires Validation Isn't Measurable?

Process validation substantiates that intended performance yields consistent results. Yet, as noted above, many processes' outputs can't be quantified. And inspection and testing are insufficient in some cases. Therefore, in many instances, meeting the FDA's vague “high degree of assurance” expectation for medical device process validation is an attempt to make the unmeasurable measurable in some manner. Such is the case when problems in medical devices are undetectable until they're actually in use (e.g., it is impossible to precisely know the longevity of a knee replacement component until after it has been surgically implanted in a patient and the device is actively in use). In other situations, validation may not be possible without a cost-prohibitive deconstruction of the device.

Tartal recommends validating all automated processes whenever possible but notes that each manufacturer must decide on a case-by-case basis whether manufacturing process validation is required.⁵

How Do I Identify Processes That Require Validation?

The FDA does not offer guidance regarding processes that specifically require validation, other than four processes identified in the preamble of the QSR (sterilization, injection molding, aseptic processing, and welding). The agency instead has historically pointed to the Global Harmonization Task Force (GHTF) Process Validation Guidance as the best advice on meeting medical device validation expectations.

The GHTF guidance identifies two fundamental questions that medical device manufacturers should ask to determine if process validation is required:

• Is the process output verifiable?
• Is verification sufficient and cost effective?⁶

If the answer to both is no, the GHTF guidelines recommend that the process should be validated, or that the process and/or product potentially needs to be redesigned.

A medical device manufacturer's decision to validate a process up front is the most cost-effective measure in many scenarios. Manufacturing process validation enhances control over factors like variations, which typically results in benefits like optimized operations, increased yields, and reduced scrap. Taking into account these types of measurable impacts that tie directly to the bottom line, the relative cost of validating a wide variety of processes may outweigh, or in many cases even reduce, the cost of inspection.

As Tartal summarized these kinds of scenarios, “You may have a process that can be fully verified, but the test is cost prohibitive, which is not an FDA concern but still is your concern. Therefore, you may want to validate.”⁷

Learn More About Medical Device Validation

For a deeper analysis of process validation requirements and objectives, see this Process Validation for Medical Devices article.

References:

1. “Quality System Regulation Process Validation,” Joseph Tartal, FDA Small Business Regulatory Education for Industry, Sept. 30, 2015.
2. “Medical Devices; Current Good Manufacturing Practice (CGMP) Final Rule; Quality System Regulation,” Federal Register, Oct. 7, 1996.
3. “Purchasing Controls and Process Validation,” CDRH Learn Industry Basics Workshop, November 2015.
4. <a cfrsearch.cfm?cfrpart="820''">21 CFR Part 820 - Quality System Regulation, updated March 29, 2022.
5. Supra note 1.
6. “ Quality Management Systems - Process Validation Guidance,” GHTF, January 2004.
7. Supra note 1.