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October 24, 2019

Understanding the cell and gene therapy (CGT) development process from start to finish often comes down to learning the language. For individuals more familiar with the early R&D steps in this process, terms like IQ, OQ and PQ – associated with later manufacturing steps – may be completely new. To get us started: IQ stands for installation qualification; OQ is operational qualification; and, PQ is performance qualification. Simply put, these are three steps in a validation process that ensures the equipment used in manufacturing works the way it’s supposed to. 

Health Canada and FDA guidance documents will frequently refer to IQ, OQ and PQ where requirements for equipment are outlined. Understanding IQ, OQ and PQ will set you up for success in transferring your process to a good manufacturing practices (GMP) facility. Developers that are savvy about validation will be able to create appropriate timelines, source the right professionals to do the job, and prepare the necessary documentation well in advance.

In fact, the validation process begins with the developer/client. The quality assurance and operations professional who carries out your validation will ask for a User Requirement Specification document (URS) that outlines exactly what you need your equipment to do. Once they have this information, the validation process can begin.

Installation Qualification Determines Whether Facilities Are Appropriate for the Piece of Equipment

Installation qualification (IQ) confirms that a given piece of equipment functions as per the manufacturer’s specifications. Installation requirements most commonly include utilities, space and software. The number of requirements will vary depending on the equipment. Another important part of IQ is ensuring that the documentation associated with the given equipment is completely executed, with all results passing acceptance criteria, and that records are readily available for anyone using the equipment. If a manufacturing process is out-sourced to a certified GMP facility, all equipment used to manufacture and perform testing should have gone through this process. However, if a new piece of equipment, specific to a process, is required, it is important to ensure that the facility is built to accommodate the operation of the equipment in terms of space, utilities and any other installation requirements. The IQ step may seem obvious, but it is essential, and will almost certainly avoid problems and delays down the road.

Operational Qualification Will Test Equipment Parameters

One of the main goals of OQ is to determine whether every part of the equipment operates as intended. Essentially, this step tests every feature listed in the manufacturer’s manual and documents it. Documentation of successful OQ testing can include photos and videos. For example, OQ of a Biological Safety Cabinet requires smoke studies that test for airflow patterns according to the unit’s “class” classification. This test is typically video recorded and reported in the OQ document. When it comes to OQ, seeing really is believing!

In addition, OQ is a stage of testing where the equipment undergoes stress testing and the process gets scientific. Operations professionals will run “experiments” to determine whether equipment can operate at the thresholds described by the manufacturer. For example: “Can a centrifuge spin at the top speed listed in the product specifications?” If the answer is no, OQ will determine the actual top speed for that centrifuge and ensure this meets the needs outlined in the URS.

Performance Qualification Will Ensure Your Equipment Is Fit for Purpose

Performance qualification (PQ) proves that if the equipment is used as intended it will give the desired result. For example: “If a centrifuge is being run at top speed, will you obtain the desired fractions in your sample?” This step is often the most varied because it depends on the specifications set out in the URS.

CGT manufacturing facilities are often controlled by a Building Automation System (BAS), which has strict requirements for area classifications as outlined by ISO 14644-1. PQ for the BAS is a great example of a unique method of qualification as it requires multiple days, and sometimes weeks, of data gathering from the facility for trending data and setting operational limits.

Once IQ, OQ and PQ documentation have been completed, they will undergo review and approval by the quality assurance team. Consider this another step in the process that needs to be worked into your timeline.

Qualification Is the Basis for Producing Safe, Consistent CGT Products

Why are IQ, OQ, and PQ so important for the manufacturing of CGTs? First, any product that is intended for use in humans will need to meet regulatory requirements. Regulations extend to all equipment used in the manufacturing process. Validation procedures that encompass IQ, OQ and PQ are required to prove that a products meets regulatory standards.

Ultimately, validation documents act as a road map that you can use to retrace your steps if your process doesn’t work. CGTs are living therapies, with many factors that influence successful manufacturing. The ability to quickly and decisively rule out equipment malfunction as the reason for a failed manufacturing run will ensure that you get to the root of the problem faster.

It is also important to remember that even though validation is a prescribed process, there is no one-size-fits-all solution. The qualification documents provided by equipment vendors are not sufficient. Equipment validation should be tailored to the specific requirements of a process. This is best accomplished by working with experienced professionals who can guide you.

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