According to the FDA, “the term qualification refers to activities undertaken to demonstrate that utilities and equipment are suitable for their intended use and perform properly. These activities necessarily precede manufacturing products at the commercial scale.”
Qualification can be further broken down into three phases: installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ), or IQ OQ PQ.
IQ OQ PQ is most commonly used in heavily regulated industries and in cases where product quality can affect consumer safety, including pharmaceuticals, medical devices, food, aerospace, and labs involved in R&D or testing inthese areas (note that several of these are FDA-regulated). These are areas where current Good Manufacturing Practices (cGMP) are generally applied, and many of the concepts in IQ OQ PQ will be familiar to those with a knowledge of cGMP.
When done correctly, the three phases of qualification are meticulous and time-consuming. However, they are critical to ensuring repeatable processes and stable product quality, and are important components of an overall validation plan. In addition, they provide rigorous guidelines to bring equipment online systematically and in a compliant manner.
In this article, we provide an overview of how organizations can successfully navigate IQ OQ PQ, and share examples of how they are used as part of a larger overall plan to maintain a robust QA system.
Validation, and the qualification steps involved, are covered by various parts of 21 CFR 211 (pharmaceuticals) and 21 CFR 820 (medical devices), and are enforced by the FDA. In this context, “validation” refers to the use of objective evidence to confirm that a process, and the equipment used in the process, will consistently meet its intended specifications. It is used in cases where verification (confirmation by direct examination) is not feasible.
As an example, consider the startup of a new reactor that is part of a pharmaceutical manufacturing line:
IQ OQ PQ can be thought of as a set of procedures, but a critical output of all three is a document that provides evidence that qualification standards have been met. As with any procedure done as part of cGMP, complete and accurate record-keeping is essential. Recall the ALCOA standard for data collection: attributable, legible, contemporaneous, original, and accurate.
It is recommended that the team involved in validation, including IQ OQ PQ, should be cross-functional, with a diversity of expertise. Various parts of 21 CFR also state that, “Each manufacturer shall ensure that validated processes are performed by qualified individual(s)”, and that personnel and consultants involved in all aspects of cGMP are required to have the proper “education, training, and experience, or any combination thereof”. Often, the range and depth of required expertise isn’t available in-house, and external consulting is required.
In IQ and OQ, either a single piece of equipment, or entire integrated systems can be qualified. An example of an integrated system is equipment designed to apply antimicrobials to food, which might be made up of individual parts like feed tanks, sprayers, a conveyor system, pumps, motors, and measurement systems.
In some cases, IQ and OQ are grouped together into an “equipment qualification”, and in others PQ is considered part of process validation. Here, we will treat each of the three protocols separately.
The main goals of IQ are to verify that:
Two sources of information that should be extensively consulted are the equipment manufacturer’s documentation for installation, and the specifications set by the process design.
Specifically, before installation has taken place, issues that should be checked include:
Often, some form of qualification testing is done by the equipment manufacturer prior to shipment. Reviewing and documenting those tests should be part of IQ, but these tests are generally insufficient to represent a full IQ on their own. In this case, it is the responsibility of the customer to validate proper installation and operation of the equipment.
The second part of IQ is confirming proper installation. In most cases, this involves a thorough review of the manufacturer’s installation guidelines for the equipment and any associated sub-systems. Questions that should be covered include:
Examples of the type of problems that can be uncovered during IQ range from minor setbacks (for example, the supplier sending a pump configured for 220 V power, when a 110 V outlet is available for the pump) to major quality issues, like the wrong type of spray nozzles being installed on a food container sanitation unit.
Any important data or previous records related to the equipment is collected and recorded as part of IQ. Recall that the central theme of any cGMP program is a thorough and complete data record. Examples of the additional information that would be collected includes:
In this process, Commissioning and Qualification (C&Q) engineers are responsible for familiarizing themselves with the manufacturers guidelines to a level where the guidelines can be understood and followed. They also need to have a deep understanding of the process requirements for the equipment, and the utilities available for equipment connection.
In addition to the primary goal of ensuring product quality and protecting consumer safety, good IQ guidelines also provide a framework to bring new equipment into the plant with minimal unnecessary delays. For example, some of the simple checks discussed here, in addition to ensuring product quality, can also prevent the need for costly reconfiguration of improperly installed equipment later.
In OQ, we begin to understand and qualify how the operational parameters of the equipment will affect the in-process material. There are two aspects to OQ. The first is to confirm that the equipment in fact operates according to the specifications verified during IQ. This could include:
Keep in mind that documenting all of these procedures, in a way that provides objective evidence that the equipment is running properly, is a critical aspect to OQ.
As with IQ, there may be testing done before shipment of the equipment to confirm expected operation (sometimes called a “Factory Acceptance Test”), but additional operational testing is needed for a full OQ.
The second aspect of OQ is to determine how the operational parameters of the equipment (things like temperature, pressure, or process times) will affect the properties of the processed material. This can include:
OQ should also involve documenting operating procedures, incoming material specifications, and process change control protocols.
Examples of issues that would be identified by OQ include:
This part of the qualification process requires skilled engineers who have a thorough understanding of the individual piece of equipment, so they’re able to understand its operational ranges, as well as the role the equipment plays in the overall process. Regarding the latter, consider this recommendation from the FDA: “Focusing exclusively on qualification efforts without also understanding the manufacturing process and associated variations may not lead to adequate assurance of quality.”
The final stage in IQ OQ PQ is where we at last confirm that the equipment functions as intended under actual process conditions, and that running the manufacturing line as a whole using the process parameters set in DQ and verified in OQ results in the final product meeting its intended specs. Specifically, this should include:
Implicit in these items is that the process has been fully documented, including standard operating procedures (SOPs) for all equipment, sampling and test plans for in-process and finished materials, plans for action when the process is found to be out of control (nonconformance contingency plans), as well as pre-defined acceptance criteria for the process.
Examples of some issues that could be revealed at the PQ stage are:
Note that in their guidance, the FDA uses the term PQ to mean “process qualification”, which covers the qualification of the equipment (as discussed in this article) and the overall process. Specifically, they break PQ into:
For more information on this please see the FDA guidance for industry on process validation.
IQ OQ PQ is a complicated, detail-oriented set of cGMP protocols designed to validate that individual pieces of equipment are built and configured for their intended purpose, installed correctly, and operate as intended as part of a manufacturing line. Furthermore, these procedures establish statistical process control parameters that will be used continuously to determine that the process is running in control.
While these protocols are time and labor-intensive, they are critical to assuring consumer safety and regulatory compliance in highly regulated industries, particularly where direct verification of the final material is not possible. Furthermore, they represent a set of standardized, systematic steps that can be followed to ensure equipment is specified and operated correctly. Proper OQ and PQ, in particular, can be useful in identifying and fixing problems in the manufacturing process if they arise.
Questions about IQ OQ PQ or other validation needs? Contact Dickson today.
About the author: Before coming to Dickson, Director of Services Antoine Nguyen spent more than 18 years in quality and validation roles in the pharmaceutical and medical device industries.