If you manufacture high value product, you should be concerned with cleanliness, contamination control, and reliability. Two new documents that are directed at the medical device community provide sensible, practical guidance for all manufacturers of high value product.
Guidance for validation of cleaning processes
ASTM standard F3127-16: “Guide for Validating Cleaning Processes Used During the Manufacture of Medical Devices” is a gold mine of useful approaches and procedures. While the scope of this newly published standard is limited to cleaning of single use medical devices during manufacture and prior to use, the document draws on knowledge from other high-value product including semiconductors, electronics, cleaning for oxygen environments, and aerospace. The comprehensive standard is a guidance document for developing and validating a cleaning process, not a step-by-step recipe.
The detailed validation flowchart in the guidance document is a useful, adaptable resource. The approach encompasses the concept of “validation readiness” through process understanding and documentation. It emphasizes the importance of cleaning throughout the supply chain as opposed to depending on final cleaning. It also includes the concept that validation is not a one-time only event and instead alludes to ongoing validation and monitoring.1
The first decision point on the flowchart poses the question, “Is the device designed for cleanability?” This brings up our all-important issue of establishing communication between designers, assemblers, and quality managers. It is essential to achieve appropriate product safety and performance. We sometimes quip that the first step is to tie design engineers to a chair with duct tape and force them to try to assemble and clean a prototype of their proposed design. In actuality, a kinder, more productive approach to implementing the guidance document is to set up a manufacturing team early on in product development and to include design engineers.
The phrase “regulatory issues” tends to evoke the FDA. However, there are other regulatory issues — worker safety and environmental compliance. The ASTM guide does not specifically address the mechanism of achieving safety and environmental compliance. Attendees at a recent program for critical cleaning in the life-sciences expressed frustration over pronouncements about allowable chemicals and activities voiced by their safety and environmental groups. Rather than avoidance, exclusion, or analogous use of duct tape, we suggest that safety and environmental professionals also be involved in product development. With the correct engineering controls, it is usually possible to implement cleaning processes that meet safety and environmental requirements while assuring product/patient safety.
The guide is comprehensive. Other sections include approaches and procedures for determining the scope of contaminating materials, risk analysis, and developing limits of acceptable residue. Considerable detail is provided regarding both specific and non-specific analytical methods, in approaches to selecting the appropriate techniques for the application. The guide also recognizes the importance of sampling techniques.
One layer at a time
Additive manufacturing (3D printing) is entering the mainstream of manufacturing. The FDA has responded with an encompassing, interactive approach. In May 2016, the FDA Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) issued a draft guidance document.2
The FDA hosted a workshop in 2014 to explore issues that might arise with medical devices manufactured by additive manufacturing.3 The 2016 draft guidance document builds on ideas and concerns presented at this workshop.
What are some potential issues for cleaning and contamination control? Design for cleanability is an even greater concern with additive manufacturing. Additive manufacturing enables the design of complex shaped devices. Devices could be designed to contain inner recesses that are difficult to access. Cleaning and/or rinsing fluids need to access surfaces and be removed from those surfaces in order to have adequate cleaning function. Validation of both cleaning and sterilization requires access to these surfaces to verify that the cleaning or sterilization process has occurred.
The order of manufacturing can be different for additive manufacturing than for traditional. Consider a bone replacement device that contains an external porous region to enable biological attachment (osseointegration) to living bone. A traditional technique might begin with machining, followed by cleaning to remove machining fluids, followed by coating with a porous layer. In contrast, with 3D printing, the porous layer might be fabricated as part of the initial build. Any post-printing machining and cleaning would be complicated by the presence of the porous layer.
On primary strength of additive manufacturing, especially for medical devices, is that the technology enables an economically feasible approach to “one-offs.” Patient-specific devices raise the variations in dimensions and shapes. This in turn raises the issue of cleanability and of cleaning validation. Still more contamination and cleaning issues can occur due to one of the primary strengths of the additive approach, the ability to economically fabricate patient specific devices. Variations in dimensions and shapes can complicate both cleaning and cleaning validation.
Back to ASTM
Industry standards and guides will continue to be developed or adapted in response to new technologies like additive manufacturing. In May, the ASTM F04 Committee on Medical and Surgical Materials and Devices held a workshop on Additive Manufacturing for Medical Applications4 in order to explore the need for new or revised ASTM standards. FDA CDRH personnel helped to plan and conduct the workshop. In our own view, additive manufacturing may not require an entirely new set of industry standards but rather a mindfulness of which standards might need to be modified to meet new challenges.
1. Kanegsberg, B. “‘Perfect’ Cleaning Process? New Guidance,” Clean Source, August 2016. http://bfksolutions.com/perfect-cleaning-process-new-guidance/
2. FDA draft document, “Technical Considerations for Additive Manufactured Devices; Draft Guidance for Industry and Food and Drug Administration Staff.”
3. Kanegsberg, B., E. Kanegsberg. “FDA Additive Manufacturing Workshop,” Controlled Environments, January/February 2015. http://www.cemag.us/article/2015/01/fda-additive-manufacturing-workshop
4. ASTM Workshop On Additive Manufacturing for Medical Applications, https://www.astm.org/MEETINGS/SYMPOSIAPROGRAMS/F04ID3044.pdf