ISO 14698 or EN 17141: Is There a Choice for Cleanroom Compliance?

In August 2020, the European Committee for Standardization (CEN) published EN 17141,¹ with the new standard superseding EN 14698-1:2003² and ISO 14698-2:2003.³ This process has caused some confusion as to which standard medical device manufacturers should follow in their efforts to control microorganisms in cleanrooms and controlled environments.

This article will attempt to resolve the perplexity that this new standard has caused and describe what will happen moving forward, though it will not seek to provide a thorough comparison between the standards.

Cleanroom Compliance Standards: Historical Perspective

Nearly 30 years ago, the International Organization for Standardization (ISO) created technical committee (TC) 209 (Cleanrooms and associated controlled environments). The mission of ISO/TC 209 was (and still is) to develop international standards for cleanrooms and associated controlled environments. These standards provide requirements and guidance on normalizing facilities and operations for industries across the world that utilize these special manufacturing environments with the goal of minimizing various types of contamination. As stated on the ISO website, the scope of ISO/TC 209 is “Standardization for cleanrooms and associated controlled environments for controlling cleanliness, as well as other attributes and characteristics, relating to facilities, sustainability, equipment, processes and operations.”⁴

The first working group (WG) formed for the TC focused on the classification of cleanroom environments based on airborne (nonviable) particle concentrations and initiated the standards that became the start of the ISO 14644 series. WG2 focused on “viables” (i.e., microorganisms in cleanroom environments and their control). This biocontamination control covers not only airborne contamination but also contamination on surfaces and in liquids. The collaborations of members of WG2 resulted in the development of the ISO 14698 series.

The 14698 series includes ISO 14698-1, Cleanrooms and associated controlled environments—Biocontamination control—Part 1: General principles and methods, and ISO 14698-2, Cleanrooms and associated controlled environments—Biocontamination control—Part 2: Evaluation and interpretation of biocontamination data.

• •Part 1 describes the principles and basic methodology for a formal system to assess and control biocontamination in cleanrooms. The formal system is the means to identify potential hazards, determine the likelihood of occurrence, designate zones of risk, establish corrective and preventive actions, and provide proper documentation. This was an early attempt to set in place what is more recently emphasized and added to standards about risk assessment and management. Part 1 also provides guidance (through the annexes) on airborne biocontamination; validation of air samplers; measurement of biocontamination on surfaces, textiles, laundry, and garments; and provision of training to personnel.
• •Part 2 provides guidance on the evaluation and interpretation of biocontamination data. Sampling techniques, time factors, culturing techniques, and analysis methods are items of discussion for monitoring (both for validation and routine).

A key point of both 14698-1 and -2 is that no limits were established regarding microbial counts. It was a sticking item during the meetings, with some countries wanting hard limits and others debating that these limits should not be included because limits would be too strict for some industries and too high for others. The argument for limits based on risk won out, and the subject of alert and action limits, as well as target levels, was in the approved versions of these documents.

Discussions on revising the 14698 series have occurred since their approval in 2003. Systematic ballots were sent to the voting member countries, but the series was reapproved each time. In the mid-2010s, an effort was made to reorganize WG2 and commence a serious effort on the revision process. This was quickly shelved due to inadequate participation from voting members in this WG.

Some voting members of WG2 from countries in Europe truly believed that the 14698 series had limited application and that changes were needed. As a result, in 2016, CEN, through TC CEN/TC 243/WG5, worked on revising and updating the CEN versions of 14698. The result was the new EN 17141 standard, Cleanrooms and associated controlled environments—Biocontamination control. Upon completion, the CEN member countries, which included the United Kingdom, voted unanimously to withdraw the 14698 series as approved CEN standards, replacing them with 17141.

EN 17141: Adding Substance to Previous Offerings

EN 17141 is a refinement of the 14698 series, combining the series into one document and updating the guidance to be more in line with current ideas of risk assessment and management. The standard adds substance to the general ideas of establishing microbiological control and demonstration of that control. It also includes a section on microbiological measurement methods. Of note, the WG made a decision not to address the biocontamination control of liquids, which was included in the scope of the 14698 series.

Another highlight of 17141 is that some of the annexes provide guidance on applying the standard to various industries (pharmaceutical, biopharmaceutical, medical device, hospital/healthcare, and food)—information that was not described in the 14698 series. Other annexes address the validation of sampling methods and explain the use of rapid microbiological methods, which are much more common now than they were in 2003.

Addressing Uncertainty: Which Standard to Follow?

With both standards (ISO 14698 series and EN 17141) currently approved and effective, confusion and uncertainty seem to have resulted. What does this mean for medical device manufacturers around the world? Which standard is to be used or followed, and how do companies remain compliant? What affect does Brexit have, even though the UK voted with CEN to supersede 14698-1 and -2?

EN 17141:2020 is the valid biocontamination control standard for Europe. This change affects only Europe, specifically those countries that participate with CEN. ISO 14698-1 and -2 are the biocontamination control standards for the rest of the world, where they have been adopted. (Note: This ISO 14698 series was never adopted as standards in the United States by the American National Standards Institute and they are not considered consensus standards by the Food and Drug Administration.)

CEN/TC 243 has proposed 17141 for inclusion in the ISO 14644 family of standards, in order to harmonize the approach to biocontamination control in air and on surfaces with that of particles and other contaminants. Within ISO/TC 209, a ballot inquiry was done in 2020 to gain input on the 14698 series. Most members agreed that it was time to start the revision process. ISO/ TC 209, during its plenary meetings late in 2020, agreed to open WG2 and reorganize it as steps to begin the revision process. It was agreed that 17141 would be the basis for the revision process, or in other words, it would be used as a starting point, then built upon by the WG2 members. It will not be wholly submitted and accepted as a replacement for the 14698 series, as some had originally hoped. This revision process will take 18 to 36 months, at the end of which will be a new 14698 standard—along with the expectation that CEN will adopt it and withdraw 17141.

In the meantime, both standards are effective. For manufacturers that market product in both Europe and the rest of the world, both standards will apply. If marketing only in Europe, manufacturers should be following 17141. Even though Brexit has happened, trade agreements and regulations remain in place, allowing for a transition over time rather than immediately. No known effort has occurred to revert back to the 14698 series, and it appears that the UK will continue with 17141 despite Brexit.

Conclusion

Each medical device company should compare the ISO 14698 series and EN 17141 and identify potential gaps in compliance, in order to avoid putting the company at risk. In the ever-changing world of regulations, this process is normal. It is anticipated that the possibility of having to conform to two standards will last a short time and that biocontamination control within cleanrooms and controlled environments will be harmonized under a single standard from ISO.