Update: Standards for Biomedical Devices
Barbara Kanegsberg and Ed Kanegsberg, October 2003
An ASTM workshop and subcommittee (ASTM F04.15.17) focused on the cleanliness
of synthetic, implantable biomedical devices took place in early May, 2003
in Kansas City, MO. The workshop was impressive in terms of the all encompassing,
positive participation by 50 attendees. The following comments and questions
at the workshop and committee meeting are illustrative of the dynamic, spirited
interchange and of the complexity, and challenge of developing cleanliness
standards for critical applications.
Defining Zero Contamination
This is related to the perennial question “how clean is clean?” Many commentary indicated that it is impossible to define zero contamination. Just as zero contamination is not readily demonstrable, appropriate cleanliness is likely to be application-specific.
Benchmarking
There is growing enthusiasm for determining how clean is clean enough by measuring residue on parts with a good history of clinical success. This benchmarking process is analogous to the concept of normal range or reference range in clinical chemistry, where healthy individuals are used to established desirable blood levels of a given analyte. However: what is healthy? What is a successful clinical history? Any consortium would need to identify both immediate biological inflammatory responses and longer-term, less-obvious, and perhaps more insidious responses to contamination.
Cross-fertilization of Technology
Some approaches to cleanliness, contamination control, and acceptable contamination levels used historically in clean industries or for critical applications are likely to be adaptable for medical devices. Conversely, one would expect standards and approaches to setting standards to be adaptable to critical areas of manufacturing such as aerospace.
Identifying Cleaning Steps; Sources of Contamination
We need to more clearly identify manufacturing steps which actually minimize contamination, whether or not they are termed cleaning steps. Seemingly non-critical processing and machining materials may contribute to contamination or to surface quality. Contamination can also occur after the manufacturing process from packaging, and plasticizers or lotions added to surgical gloves.Sterility Versus Cleanliness Sterility must be distinguished from cleanliness. The contribution of formerly living (but no longer viable) materials to inflammatory responses and/or long-term performance can be significant. Endotoxins, lipopolysaccharides which are remnants of the cell walls of gram-negative bacterial cell walls, are non-viable, biological-based potential sources of contamination. Although once part of living cells, they are not removed by autoclaving.
Defining the surface in discussing surface contamination, how do we define a surface?
Even seemingly impervious surfaces
may exhibit porosity or cracking at the micro-level. Contamination
can gradually “leach
out” of
underlying layers.Extraction and Analysis of Contaminants
Extracting, identifying, and quantifying adherent
soils is increasingly of
concern, particularly
where the product must perform reliably for long
periods of time. In addition, it is recognized that
there are
benefits and limitations
of location-specfic
microanalysis
versus extractive analysis of the entire object.
However, if extraction is
chosen, what is a reasonable representative sample?
How should larger objects be extracted? Given the
number
of steps in many
device manufacturing processes
there is the problem of the unexpected residue. What
if an unexpected residue is discovered? How does
one plan for unexpected residue?
Immediate Plans
The committee is currently developing a series of analytical test standards. First, standards for quantifying and characterizing contaminants are developed. Ultimately, acceptable cleanliness levels will be developed. The committee meeting focused primarily on extraction techniques. Some issues include ultrasound versus refluxing, the choice of organic solvent or water, and other specific concerns in extraction technique such as numbers of parts to be extracted and specifics of beakers.
The Near Future
The key to development of encompassing consensus standards is participation by a range of knowledgeable, interested parties. The next meeting of the F04 committee is scheduled for November 20, 2003 in Tampa Florida; and a symposium is scheduled in 2005. Now is the time to become involved in this important effort. We’ll keep you posted on progress in future columns.The authors wish to acknowledge the input of Steve Spiegelberg, Polymer Technology.
Reference:
Kanegsberg and Kanegsberg, Dead Dirt and Bio-Dirt,
A2C2, April, 2003.
Note: Additional information regarding the
F04 committee,
the workshop, and copies of some presentations
(including one by B. Kanegsberg) can be obtained
at: http://www.campoly.com/cleanliness.html
Barbara Kanegsberg and Ed Kanegsberg are independent consultants in critical cleaning, precision cleaning, surface preparation, and contamination control. They are the editors of “Handbook for Critical Cleaning,” CRC Press. Contact them at BFK Solutions LLC., 310-459-3614; info@bfksolutions.com; www.bfksolutions.com.
