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This is an example of a table that would be included in a qualification protocol in a prerequisites test section. An official copy of the protocol is printed and the tester fills in results of the procedure for the test section performed.
Equipment qualification is a necessary and critical step in ensuring that a product or service is provided accurately and consistently with requirements aligned with medical device manufacturing and testing. This is especially critical for the medical device industry because the medical device manufactured by a company is considered a piece of equipment and requires qualification, as much as other equipment and instruments involved in manufacturing. Verifying prerequisites before qualification ensures a safe and smooth qualification process. A prerequisite in an equipment qualification is a documented verification intended to demonstrate that everything is in order prior to initiating the execution of the qualification section.
For medical device companies, using prerequisites translates into less time and money spent on avoidable delays. Because the requirements for a piece of equipment or a device can vary widely from company to company and even between pieces of the same type of equipment, it is important to devise a universal set of prerequisites that will address all potential trouble areas. Device OEMs and device-testing facilities need to understand how prerequisites fit into an equipment qualification, and need to know what should be Checked during prerequisite verifications in an equipment qualification. They should also be able to outline a universal set of prerequisites.
Prerequisites in an Equipment Qualification Protocol
Setting up equipment in a medical device manufacturing facility includes ensuring that the equipment will safely and consistently work as intended. To do this, it is necessary to verify the following actions:
- That the equipment is installed according to the manufacturer's instructions.
- That the equipment is operated properly and consistently.
- That the equipment performs within the requirements determined by the facility.
To cover all of the necessary criteria, equipment qualifications are typically organized by separating the protocol into three sections: installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ).
Because the IQ, OQ, and PQ are performed separately, each should have its own set of prerequisite verifications. Because the equipment requirements at each of the qualification stages are different, the prerequisite requirements at each of the qualification stages should be different as well.
What to Verify during Prerequisite Testing
The general goal of prerequisite testing is to ensure that items that commonly cause execution to be delayed or repeated are in order prior to starting the qualification. Because of variations in equipment and differences in how facilities operate, using the exact same prerequisite verifications may not always be the best approach.
For prerequisites to significantly help streamline the qualification process, they have to be tailored to fit the specifics of both the equipment and the facility. As a whole, it is easy to overlook potentially important prerequisites. Therefore, it is often helpful to separate them into categories and address them one at a time. With a good understanding of the categories, the process of tailoring the verifications to suit a specific piece of equipment at a specific facility will be much smoother. Although it is nearly impossible to cover all prerequisite verifications, some of the most common prerequisite categories are presented and explained in the following paragraphs.
Procedure verification includes any procedure that is required for operation or maintenance of the equipment as well as any sampling or testing procedures required to obtain and analyze the protocol samples. Each of these procedures has typical items that need verification, such as the status of the procedure, the title, and the document number. Specifications vary depending on the section of the protocol the verification is being written for (i.e., IQ, OQ, or PQ). For example, during the IQ, it might be acceptable for the procedures to still be in draft form. But by the time the PQ section is going to be executed, the procedures must be approved documents.
Performing procedure verification could be cost-efficient for a company. For example, a medical device facility brought in personnel to perform the time-consuming task of collecting microbial samples for a qualification. When the samples arrived at the laboratory, they realized that the testing procedure for the samples was still in development. None of the samples taken were usable and the entire collection process had to be repeated once the testing procedure was approved. Because of the delays, the launch of the medical device into the market had to be postponed. The expense of the wasted man-hours and supplies and the delay of the launch could have easily been avoided by a procedure verification prerequisite.
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Procedure prerequisite specifications in equipment qualification.
The importance of verifying the training of operators and test personnel is a universal prerequisite throughout the various types of validations and qualifications. For equipment qualification, it's important to verify that the personnel operating the equipment (in addition to the personnel executing the protocol) have the training required to successfully perform the necessary tasks according to the currently acceptable method. Additionally, the personnel executing the protocol should be similarly trained.
Picture executing a performance qualification of an autoclave for which the operator doesn't know how to control the equipment, and the importance of verifying operator training becomes clear. What may not seem as clear is why it is important to verify the training of the qualification test personnel. A medical device manufacturer learned the importance of test personnel training during the qualification of a freezer. The freezer qualification included a 72-hour temperature mapping, which required monitoring and recording the temperature in different quadrants of the freezer at specified time intervals for a three-day period. During an audit, it was discovered that the data were not collected for the full 72 hours. An investigation concluded that the error was due to the fact that the testers who set up the mapping were trained on an earlier revision of the protocol and didn't realize the time interval had changed. For this company, the small amount of time that would have been needed to execute a prerequisite seems well worth it after being set back three or more days because of the need to investigate and repeat the test.
Although not actually a part of the equipment, utilities are essential to its operation. Equipment cannot run without electricity, compressed air, gas, water, etc. Utilities that should be Checked include any utility that is required to execute the protocol and has the possibility of not being available or not being available at the required level.
An example of the benefit of performing utility verifications was seen during the qualification of equipment designed to weld the seam of a medical device. For the equipment to produce a successful weld, it was critical that the laser power supply meet very specific electrical requirements. During the qualification, multiple unsuccessful welds were observed. After a lengthy investigation, it was discovered that the problems were caused by a variation in the electricity feeding the laser. Although the problem was identified, the time needed to correct the problem and rerun the test was costly and could have been avoided had the utility qualification of the electrical system been performed prior to starting the testing.
Test Instrument Prerequisites
Instituting test instrument prerequisites is a simple way to eliminate costly delays and misunderstandings. The items that should be tested in this section include any instrument or piece of equipment that is required during the execution of the protocol. Some examples of instruments or equipment that are typically Checked in test instrument verification include voltage meters, particle counters, and scales. Testing and sampling instruments and equipment are often used by many people and often require calibration. Typical items that benefit from prerequisite testing include the availability or location of the instrument or equipment and its calibration status for the expected duration of the qualification execution. Just imagine the headache it would cause, if, when it came time to start a qualification, you realized that your scale was out of calibration or the particle counter you ordered a month ago never arrived. Making arrangements for calibration or tracking down an order often involves time-consuming activities (e.g. getting approvals, contacting customer service representatives, and tedious paperwork). Such tasks are time-consuming in general, so don't add to the burden by waiting to do them until it's too late to resolve the issue without holding up the qualification. Performing prerequisites allows you to address the items before they start causing delays.
An incident during a qualification of an incubator at a contract testing laboratory shows how test instrument verification can make a difference in a timeline. Temperature mapping was included as part of the qualification. After completion of the qualification, it was discovered that some of the data loggers used during the mapping were out of calibration. The calibrations were scheduled and performed, but the mapping had to be repeated once the data loggers were received back from calibration. The hassle of additional scheduling and the delays incurred could have been avoided had the contract testing laboratory performed a test instrument verification that included the data loggers.
Equipment Status Prerequisite
The purpose of equipment status prerequisite testing is to ensure that the equipment being qualified is installed and ready for qualification. As with procedure verification, different requirements or specifications are typically desired for different sections of the qualification. For example, it might be necessary for the equipment to be set up, calibrated, and ready to run during a PQ. However, for the IQ, it's only necessary for the equipment to be installed. Another possible inclusion in equipment status verification is the availability of the equipment for use. Unlike process validation, which cannot begin until a process has been developed, equipment qualification protocols are sometimes written before the equipment is even received. As a result, a protocol can be ready for execution long before the equipment has arrived and been installed.
Recently, the qualification of a building management system at a medical device facility was scheduled to begin, and consultants were hired to execute the protocol. When the consultants arrived at the facility to begin the qualification, they found out that an ancillary electrical panel had not been installed because it was on back order. If the equipment status had been Checked prior to the qualification, the cost and time of the additional on-site visit by the consultants in order to reassemble the team could have been avoided.
Additional Benefits of Prerequisites
Documentation of prerequisites creates a system that actively tracks future problems, not just problems that have already occurred. When combined with the existing methods of identifying trouble areas of the quality system, prerequisites provide a little extra help in meeting the overall goal of preventing problems rather than just reacting to them.
Adding prerequisites to a validation or qualification program also helps OEMs prepare before an audit. By performing these simultaneous “spot checks” or verifications of the quality system, it is possible to generate trends in the quality system. The additional method of locating such holes and inconsistencies helps a company understand the areas to focus efforts prior to an audit instead of after an auditor has found the problems.
Incorporating prerequisites into an equipment qualification ensures that equipment is ready to run consistently and reliably. Moreover, it ensures that the equipment can pass the testing outlined in the protocol with fewer failures, investigations, or retesting. The ability of prerequisites to streamline the execution of a qualification, with the added bonus of the ways that they benefit a quality system, demonstrates the value of incorporating prerequisites into an equipment qualification. Having a clear understanding of the benefits and being able to apply them to your facility can ensure smooth, cost-effective qualification efforts.
Jennifer Medlar is a consultant for Advanced Biomedical Consulting LLC (ABC; St. Petersburg, FL), and Nancy Cafmeyer is a project manager at the company. Contact them at [email protected] and [email protected].
“Current Good Manufacturing Practice for Finished Pharmaceuticals,” Code of Federal Regulations, Part 211, Title 21, Rev. April 2006.
Food and Drug Administration (FDA), “Guideline on General Principles of Process Validation,” Rockville, MD, 1987.
N Cafmeyer and JM Lewis, “Process Validation Prerequisites 101,” Medical Device & Diagnostic Industry, March 2008.
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