What is Production Equivalence?
In the FDA’s 21 CFR Part 820: 820.30(g) Design validation requires that devices used for validation are "production units, lots, or batches, or their equivalents.”
Although 21 CFR 820.30 does not require design verification on production equivalent devices, in general, it is beneficial to perform final system-level verification, standards compliance testing, and verification of risk controls using production equivalent devices because this provides the confidence that any changes made throughout the development process did not impact the ability of the device to meet requirements.
Additionally, section 820.30(i) of the regulation regarding design changes requires verification of design changes before their implementation. Performing verification on devices manufactured from approved, documented designs, using production equivalent materials and processes facilitates compliance with this clause of the regulation.
Production units (lots and batches) are easy to identify-- they are units from the final assembly location for production, after design transfer to production, and after all production processes have been validated.
Production equivalent units, however, are not as easily understood. There are many reasons to use production equivalent units in verification as well as validation so gaining an understanding of this term is paramount.
Production equivalence infers that a manufacturer has created the test samples from controlled, approved documentation using equivalent materials and manufacturing processes to those used for the final production product.
When to use production equivalent devices?
Formal design validation requires either production units or production equivalent unit(s). If production units are not going to be used, the device manufacturer must demonstrate equivalency to production devices.
Design verification does not require production units or production equivalent unit(s) but using production equivalent devices in verification and standards compliance testing is a best practice for ensuring that test results will be repeatable on production devices and for reducing the need for significant, costly, regression testing..
For verification activities production equivalence may be established for subassemblies or parts of the system that are relevant to the testing. For example, EMC testing, and electrical performance testing may not require production tooled plastic enclosures to establish equivalence as the plastic material or tooling method (injection molding vs. 3D printing) will not impact the electrical characteristics of the device in most applications. However, using production equivalent cables and electronic subassemblies for these tests will demonstrate applicability to production devices.
How does a manufacturer establish production equivalence?
To establish production equivalence, the manufacturer must create a Device Master Record documenting the revisions of all components, assemblies, and materials used to manufacture the test samples. Any differences from production materials and processes must be justified. While the regulation is flexible, the onus is on the manufacturer to document and justify that the units/devices are equivalent.
Additionally, manufacturing processes used in creation of the test samples need to be considered. These processes must be documented and justified to be equivalent to final manufacturing processes for any production equivalent devices. These processes can include:
PCBA fabrication and soldering methods
Crimping methods and tools for wiring harnesses
Application of sealants
Assembly sequence and instructions for manual operations
Testing or burn-in operations that could affect the reliability of the device
Torque specifications for fasteners
Production equivalent devices can be manufactured:
a.) In the design and development phases in a manufacturing cell before transfer to manufacturing
b.) by the final production facility in a limited run prior to full design transfer
The manufacturing processes for either the manufacturing cell or the final production facility are documented in a Device Master Record that is created for the specific purpose of building up a number of devices for V&V.
The manufacturer is also responsible for ensuring that the devices used for validation, particularly those that will be used in field studies or clinical trials, are safe and have mitigated identified risks, including the risks of the device to patient safety and risks related to the manufacturing process that could compromise patient safety.
Some of the design validation performance and functionality activities will need to be repeated once the design is transferred from the design and development to the regular production facility. Producing test samples from controlled documentation, and using documented processes, facilitates identifying the scope of regression testing required from any changes that may occur after transfer to the production facility.
If a 510K or CE Technical File was filed using the cell manufactured device, it is critical in the transfer to final production to capture and mitigate any new risks introduced from changes in processes. If any changes introduce new risks, then it is possible that a resubmission might be required for an update to the 510 K or CE Technical File,
What are the advantages of utilizing a small manufacturing cell to fabricate production equivalent devices?
There are advantages to creating production equivalent devices in a small manufacturing cell. These advantages include:
Shortening the amount of time required to get units that are suitable for verification, and, in certain instances, validation.
Ability to develop and perfect processes prior to transfer to a production facility.
Early verification of the device to agency standards. Performing agency standard testing early in the device design process allows the ability to assess device compliance and identify any changes that may be required. This is especially beneficial when there is a high likelihood that very little is going to change about the device in the final production facility production process. A design history file and a device verification record can be created that include agencies submission results and reports prior to transfer to the final production facility.
Ability to identify changes to the product prior to investing in high-volume production tooling, test fixtures, and production line setup.
Changes resulting from verification testing can be implemented for regression testing faster than if the final production facility was manufacturing the devices.
The manufacturing cell can be used while the final production facility is getting ramped up. Any changes and/or mitigations that occurred during the manufacturing cell production can be introduced to the device production facility during their validation process.
Manufacturers may not want to ramp up production for a limited number of devices going into verification or validation.
Therefore, a pre-production manufacturing cell has benefits as long as it is properly set up with documented processes that are equivalent to the final production facility processes.
To demonstrate the unit is production equivalent, the following criteria must be met:
The units are made in a manufacturing cell (or production facility) from controlled, approved design documentation.
The units are made with equivalent components & materials that went through an in-coming acceptance activity with approved acceptance criteria.
The units are made with similar equipment and tools, and manual operations are performed by personnel using similar assembly procedures and instructions as used to build the production units.
Small quantities of devices for verification and validation testing can be produced in a manufacturing cell more readily than in the final production facility after a full production transfer process. If a larger number of test samples are required, or if the device requires specialized equipment and processes not available in a pre-production cell, it may be better to create test samples using the final production facility.
Many startup companies would prefer to create a small manufacturing cell where they can manage the costs of producing a production equivalent device versus a full final production facility ramp-up which might incur large NRE costs. Understanding the requirements for creating and documenting production equivalence is key to this approach.
There are no short cuts to producing units for validation—they must be production or production equivalent. However, if test samples are manufactured using controlled, approved documentation, and use production equivalent materials and processes, the justification for production equivalence is not burdensome.