Tom Hoover, business development manager, medical, Emerson Automation Solutions discusses why equipment calibration is vital in meeting IQ, OQ and PQ requirements.
Medical devices in the US are classified by the U.S. Food and Drug Administration (FDA) into 3 primary classes – I, II or III – based on increasing risk to the user.
Under FDA regulations, there are two primary pathways for approval of your medical device or product for distribution in the US devices or products that are in the highest risk category, Class III, or that are entirely new to the market require a stringent pre-market authorisation. For devices with less risk, a 510(k) premarket submission can be used, which demonstrates that a device is substantially equivalent to, and therefore as safe and effective as an already authorised device. According to market research, FDA-dependent product development stages can account for more than 75% of the cost of bringing such products to market. And, because of the enormous potential costs of a major product recall, it is vital to demonstrate that your product, and the assembly equipment and processes that stand behind it, meets all regulatory, operational and performance requirements.
These requirements are spelled out in FDA Title 21 Code of Federal Regulations (CFR) Part 820, commonly referred to as the Quality System Regulation (QSR). Part 820 specifies that medical device manufacturers must maintain a traceable and auditable quality management system (see Figure 1). It also outlines current Good Manufacturing Practices (cGMP), which are the regulations that govern the methods, facilities and controls used in the design, manufacture, packaging, labelling, storage, installation and servicing of all finished medical devices. (Note: The FDA is in the process of harmonising Part 820/QSR requirements with those of the European Union’s Medical Device Regulation and ISO 13485.)
Figure 1: Title 21 CFR Part 820, commonly referred to as the Quality System Regulation, specifies that medical device manufacturers must maintain a traceable and auditable Quality Management System. Image courtesy of Emerson.
An integral feature of Part 820/QSR requirements is process validation. The FDA considers that a “validated” cGMP medical device manufacturing process should be developed and validated sequentially through three stages of “qualification,” each of which relies on protocols that define specific procedures needed to achieve validation at that stage. For example, qualification protocols outline procedures to establish that the equipment installed and used for medical device manufacturing demonstrably meets high reliability, consistency, throughput and quality assurance requirements at three process phases (see Figure 2):
- When it is installed (Installation Qualification [IQ]),
- When it begins or resumes production (Operational Qualification [OQ]), and
- During continuous operation over a period of time (Performance Qualification [PQ]).
Figure 2: Equipment calibration plays several vital roles in meeting IQ, OQ and PQ requirements for validated cGMP manufacturing processes. Image courtesy of Emerson
The importance of calibration
A key segment of the QSR, Part 820.72, defines the standards for inspection, measuring and test equipment used for equipment calibration, which is integral to ongoing process validation. Equipment calibration is essential for:
- Verifying the accuracy of measurements made by equipment, or their maximum level of uncertainty.
- Demonstrating the traceability of measurement accuracy/uncertainty to a national or international standard, such as the National Institute of Standards and Technology (NIST).
- Fulfilling the installation qualification of the master validation plan.
Later, after equipment has met initial Operational Qualification and Performance Qualification requirements and entered into production, ongoing calibration is essential to ensure stable performance and reliable production of high-quality medical products.
The elements of calibration
Calibration services should meet cGMP requirements. The 21 CFR Part 820.72 statutes define that:
- Equipment is routinely calibrated, inspected, checked and maintained according to requirements established by the equipment manufacturer. Typically, equipment is calibrated once per year or more often if required by the manufacturer.
- Specific directions and limits for equipment performance and accuracy are defined and documented.
- Calibration standards used for the inspection, measuring and test equipment are traceable to a national or international standard.
The vital role of the equipment calibration supplier
Because standardisation is integral to a calibration program, calibration vendors play a vital role in the process. Your validation supplier should:
- Offer a calibration program that harmonises with the requirements defined by 21 CFR Part 820.72. Part 820.72 specifically outlines the requirements for inspection, measuring and test equipment and their required calibrations.
- Use calibration equipment that is traceable to a nationally recognised standard, such as NIST. The vendor should be able to demonstrate that all of its test equipment — everything from wrenches to oscilloscopes — was recently tested and validated in an ISO 17025-accredited laboratory to ensure that it is accurate and properly functioning.
- Provide you with essential calibration documentation and labelling of your equipment. This includes a calibration label for the equipment, which contains an equipment identifier (serial or asset number) calibration date, the name of the calibration technician, and the date for the next calibration. These should be displayed on a sticker and/or in a document on or near each piece of equipment. The calibration provider must retain electronic records for all aspects of the calibration/service, including training records of the personnel who perform the calibration. Records in electronic format must be maintained for a minimum of five years.
- Offer a global footprint, with the ability to provide qualified calibration services, together with asset-tracking services, on-site at multiple manufacturing locations, minimising the need for shipment of vital production equipment to remote locations for calibration.
- Offer simultaneous equipment fitness reports that document equipment health and suggest steps for maintaining and optimising equipment performance. For example, an ultrasonic welder that has performed for millions of cycles should not only be calibrated but also assessed in terms of equipment and tooling reliability. A fitness report done by a competent vendor should also be able to indicate the need for predictive/preventive maintenance.
Figure 3: A Branson GSX ultrasonic welder from Emerson undergoing calibration. Calibration is a process that verifies the accuracy of measurements made and used by the welder, or other pieces of manufacturing equipment during operation, traceable to an internationally recognised standard.
Given the complexity and risk of medical device manufacturing, routine equipment calibration represents not only a regulatory necessity but also an operational assurance that equipment is helping to deliver reliability, consistency, quality and traceability in the devices that you produce. In a global business, a well-chosen calibration supplier may provide not only documented proof of equipment safety, performance and accuracy but also valuable additional services that simplify multisite asset tracking and identify potential reliability problems that can be addressed through predictive and preventive maintenance.