Equipment Validation in Life Sciences: A Comprehensive Guide

Controlling and documenting IQ, OQ and PQ effectively is a complex and time-consuming process for life science companies. Here’s our guide to nailing validation without compromising your velocity.

IQ, OQ, PQ - what do they mean?

IQ, OQ and PQ are the three steps of process validation that regulators such as the FDA require you to develop to ensure consistent outputs from your equipment. They each have a different role to play as you take delivery of machinery, configure it and specify how your company will use it to produce required results:

IQ (Installation Qualification)

Ensures that any equipment and systems are installed correctly and can operate according to the intended design specifications.

OQ (Operation Qualification)

Tests the equipment under a range of operating conditions to ensure it can perform reliably within the specified limits.

PQ (Performance Qualification)

Confirms that once installed and operating, the equipment consistently produces a product meeting its predetermined specifications and quality attributes.

It should be noted that in recent years, layers of complexity to equipment validation through the increasing integration of software in design and process automation.

With so many ‘moving parts’ involved in the production of complex devices and applications, it’s important to ensure that each component, both mechanical and software-based, work together exactly as intended. If they don’t, you could end up with products that don’t work correctly while putting your end users at risk of harm.

But there is often no easy way to determine that a machine is always doing exactly what it should. You can’t test every single pill that rolls off a production line. You can’t stress test every soldered part within a functioning product or unpack every sterile package you create to prove its contents are sterile. At least not without destroying the very product that you’ve just manufactured!

That’s why FDA 21 CFR 820 states that:

“Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures.”

And that’s where your IQ, OQ, and PQ processes come in.

Let’s take a look at these in more detail.

What is Installation Qualification?

First things first.

Has your equipment been delivered and installed correctly? How do you ensure a consistent approach to installation and set-up that prevents errors and omissions that lead to manufacturing missteps later on?

Installation qualification is a formal documented process that ensures delivered equipment, and all its associated parts are cross-checked against a list of specifications from the manufacturer. These typically include:

• Cross-checking the contents against packing lists - is everything there?
• Checking for damage done in transit.
• Making sure each piece of equipment is installed in the proper location.
• Checking connections to other devices or equipment.
• Verifying power supply to the device.
• Verifying that the operating conditions and environment match the manufacturer’s specifications.
• Software Compatibility Check.
• User Access and Security Settings.
• Software Functionality Test.
• Network Connectivity and Configuration.
• Storing and indexing manuals, certificates, and any other necessary documentation.
• Recording calibration and the dates of validation

What is Operational Qualification?

Once your equipment is installed, how do you ensure it is working correctly, and you understand the device's limitations?

Operational qualification is a formal documented process that ensures the equipment operates in accordance with user requirements and within the operating range specified by the device manufacturer.  

During the Operational Qualification process, various tests are carried out on the equipment to check every single function it performs. This establishes the 'operational parameters' – the conditions under which the device operates best and is most effective.

• Data Accuracy and Software Validation: Verify the precision of data collection and ensure software accuracy and reliability.
• Repeatability and Consistency Tests: Ensure the device delivers consistent and repeatable results, crucial for medical accuracy.
• Alarm and Error Handling Tests: Check all alarms and error messages for proper functioning, including software error handling.
• Maintenance and Calibration Scheduling: Establish regular maintenance and calibration to maintain device accuracy and longevity.
• Emergency and Fail-Safe Procedures: Implement and test emergency shutdown and fail-safe modes, including software contingencies.
• Training and Competency Assessment: Provide comprehensive training and assess staff competency, especially in software operation and troubleshooting.

These tests and checks are crucial because they ensure that the device not only works but works optimally and safely within the specified limits.

This process of operational specification will help you tell the people who will operate it in the future how it must be stored, used and maintained to achieve consistent results.

What is Performance Qualification?

How can you be sure your intended SOPs (standard operating procedures) will produce the right quality results time and time again? How do you know your process for handling equipment is safe and effective?

Performance qualification is a formal process to make sure that the equipment works correctly and gives the right results when used in actual working conditions.

This means that PQ tests should be done in the real place where the product will be made, with workers who know how to use the equipment. During these tests, they use exactly the same utilities, equipment, and SOPs for making the product as they will in the real-world process.

The FDA recommends establishing a PQ process that includes specifying:

• Manufacturing conditions, operational parameters, and raw materials.
• Data collection and evaluation plans.
• Equipment tests and acceptance criteria.
• An extensive sampling plan for quality assurance.
• Criteria for science- and risk-based process efficacy decisions.
• Facility design and personnel qualification and training.
• Validation status of analytical methods.
• Review and approval of the protocol by key stakeholders.

The Performance Qualification process serves a dual purpose. Firstly, it proves through documentation that you have a thoroughly tested method capable of consistently delivering the desired outcomes. Secondly, it establishes a continuous validation system to check that the process is adhered to and delivers consistent results over time.

As it says in FDA 21 CFR 820.75(b):

"Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met."

Which regulations and standards require IQ, OQ and PQ?

The IQ, OQ, and PQ process for equipment is central to the smooth functioning of your operations and the delivery of end products that are safe and efficacious. Equipment validation is a key part of GMP (Good Manufacturing Practice) and the management processes mentioned in:

• FDA Quality System Regulation (21 CRF Part 820).
• ISO 13485: 2016 Medical Devices – Quality Management System.
• GHTF Quality Management Systems – Process Validation Guidance (GHTF/SG3/N99-10:2004 Edition 2).

How best can you document and control your validation process?

Don’t forget the FDA’s definition of validation:

“Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled”

21 CFR 820.3 (z)

So, if you’re performing these equipment qualification processes right, you’ll likely generate A LOT of documentation. This burden that has been added to in recent years by the additional complexity of CSV (computer system validation) in the automation process.

All this will require a lot of checking, cross-checking and the use of fail-safe approval mechanisms to prevent mistakes and preserve validation records effectively for inspection by your auditors.

Your Quality Management System will need to store, collate, and maintain the following documents (and more) to cover all your key pieces of equipment:

• Validation master plan (MVP)
• SOPs
• Calibration records
• Approval audits
• Testing data
• QA data
• Validation matrices

Together, this documentation will power the IP, OP and PQ processes that you need to perform for every new piece of equipment you acquire. It will also be the evidence for regulators that equipment and associated processes are configured and maintained properly to deliver products that always work as intended.

Doing this within a paper system can be a nightmare of administration and organisation. Given the complexity of modern machinery and product specifications, performing them manually is likely to result in serious errors and omissions.

Without the automated digital tools to ensure secure record-keeping, keep documentation up-to-date, and collate the right documents for inspection, you may never be able to prove your equipment can deliver products of the required quality. You need a robust and automated process to ensure a consistent and error-free way of holding and handling validation documentation in the future.

But it’s also the case that regulation is continually changing and adapting to new technologies such as AI and IoT. How do you validate equipment whose behaviour is being continually altered by a self-learning algorithm?

It’s as a response to these technological advances that the FDA’s requirement for software validation is shifting towards the risk-based approach of computer software assurance (CSA) to streamline documentation requirements.

Any digital solution you choose should be flexible enough to adapt and update the validation process to meet new demands - without grinding your business to a halt.