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.
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 discus-
sion 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.
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,
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.
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.
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@example.com