In addition to the typical challenges of navigating an overwhelming conference and trade show, the 2014 MD&M West conference, held in Anaheim, Calif., provided food for thought about the current and near-future direction of medical device manufacture. As might be expected, designing, monitoring, and maintaining appropriate controlled environments will be increasingly important. In addition, current and proposed designs will require careful attention to critical cleaning, contamination control, and leachable residue.

Emphasis

The program provided multiple options for education, including futuristic predictions about 3D printers in the home, the growth of on-demand custom implantable devices, and the growth of “gaming” in device design. There were hands-on, interactive workshops. The emphasis on creative, innovative product design, including design for manufacturability, is heartening in that it meshes well with the need to design products that can be successfully cleaned, both during manufacture, and, in some cases for reuse.¹ The trend toward lifecycle approach^2,3 that is being adapted from pharma for use in device manufacture was a topic in some presentations.^4,5

Lifecycle

The goal of the three-stage lifecycle approach is to assure that a product or process remains in control throughout the product lifetime. A consequence of this approach is an emphasis on pre-validation during the design and continued monitoring after product introduction. The FDA Center for Devices and Radiological Health Strategic Priorities for 2014⁶ includes striking the right balance between pre-market and post-market data collection by shifting—when appropriate—some pre-market data needs to the post-market setting in order to reduce the time for patient access to high-quality, safe, and effective medical devices of public health importance.

Stage 1 is design and development, with the primary aim to fully understand the process so that it is suitable for routine commercial manufacturing. We are strong proponents of pre-validation, of thoughtfully designing, developing, and testing the cleaning process to be validated. Design includes establishing strategies for process control to reduce input variations and to adjust for input variations.

Stage 2 consists of proving the process works. This is the traditional validation step. It includes validation of the facility and equipment and defines a process performance qualification (PPQ). The PPQ should use sound science and experience to confirm the process design and demonstrate that the commercial manufacturing process is expected to be consistent.

Stage 3 is process maintenance. Maintaining the process includes not only process monitoring but also on-going validation. Several speakers discussed monitoring (or continuous validation or “never-ending” validation). This stage anticipates that there are likely to be changes, either planned or unplanned. It consists of establishing a program to continue to monitor and validate the process, evaluating and acting on any changes or trends.

3D printing/additive manufacturing

There was enthusiastic interest in 3D printing at both the conference and the trade show. We did not see kitchen counter versions of 3D printers, but the number of exhibitors was so extensive that a guided tour of pertinent exhibitors, complete with headset narrations, was offered to conference attendees. While the emphasis was on 3D printing with plastics, additive manufacturing has clearly moved beyond rapid prototyping applications and is being developed for more critical applications, including implantable metal devices. Given the potential for and desirability of miniature devices with very complex design and high surface area, the 4Ds of design, develop, document, and defend⁷, and the lifecycle approach will be important in additive manufacturing.

One challenge is to select and optimize cleaning processes that meet the unique conditions of additive manufacturing. The FDA Center for Devices and Radiological Health has formed an Additive Manufacturing Working Group which is spearheading efforts across the Center including guidance and standards development, review harmonization, and regulatory science priorities.

The future

In terms of process specifics, however, the emphasis at MD&M was on risk assessment, creative product design, sterilization, and on design of controlled environments. It appears to us that over the past five years, there has been decreased discussion of critical cleaning, the actual impact of contamination control on device functionality, and the impact of leachable residue. We were among the few presenters to emphasize life cycle and pre-validation in the context of critical cleaning of medical devices. On the trade show floor, however, cleaning was the focus of some excellent exhibitors and was part of at least one exhibitor presentation.⁸ It is clear that interest in critical cleaning is increasing, as evidenced by comments of people who attended our presentation or who we met during the conference and show.

Medical devices are becoming more complex. Additive manufacturing can produce shapes that are not possible or feasible to build with traditional manufacturing methods. Miniature robotics applications are increasing. With this complexity of design, challenges for cleaning are increasing. Cleaning processes must be able to access hard to reach surfaces and both the cleaning agents and soils must be adequately removed to minimize residues.

References

1. J. Broad and D. Smith, “Chapter 16: Cleaning Validation of Reusable Medical Devices: An Overview of Issues in Designing, Testing, and Labeling of Reusable Devices,” Handbook for Critical Cleaning: Applications, Processes, and Controls, CRC Press, 2011.
2. B. Kanegsberg and E. Kanegsberg, “2020 Pharma,” Controlled Environments Magazine, March 2014.
3. P. Pluta, “FDA Lifecycle Approach to Process Validation— What, Why, and How?,” Journal of Validation Technology, Spring 2011.
4. B. Kanegsberg and E. Kanegsberg, “Cleaning Validation Without Tears,” MD&M West 2014 Conference, Anaheim, CA, Feb. 2014.
5. W. Murray, “Process Validation: Decision Making, Plan Analysis and Risk,” MD&M West 2014 Conference, Anaheim, CA, Feb. 2014.
6. http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedical ProductsandTobacco/CDRH/CDRHVisionandMission/ucm 384132.htm
7. B. Kanegsberg and E. Kanegsberg, “4D Processes,” Controlled Environments Magazine, January 2014.
8. “Risk Assessment of Classified Environments & Laboratories,” Presentation by LCS Laboratories and IPS Technologies, MD&M West 2014 Show, February 13, 2014.

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Barbara Kanegsberg and Ed Kanegsberg (the Cleaning Lady and the Rocket Scientist) are experienced consultants and educators in critical and precision cleaning, surface preparation, and contamination control. Their diverse projects include medical device manufacturing, microelectronics, optics, and aerospace. Contact: [email protected]

This article appeared in the April 2014 issue of Controlled Environments.