Medical Device Link.

Originally Published IVD Technology July 2004

REGULATIONS & STANDARDS

Donald M. Powers, PhD, is president and principal consultant of Powers Consulting Services (Rochester, NY), an independent IVD regulatory and quality consulting firm, and a member of the IVD Technology editorial advisory board. He can be reached at powers@frontiernet.net.

TC212, the technical committee of the International Organization for Standardization (ISO; Geneva) founded by NCCLS (Wayne, PA) in 1995, is working on several new international IVD standards. Standards for risk management, labeling, and validation of quality control recommendations are at various stages of development. IVD manufacturers in the United States recognize the benefits of international standards and support the working groups that are developing them. 

However, when it comes time to review and vote on the draft standards, only a small percentage of U.S. IVD manufacturers have taken advantage of the opportunity. This is reflected in the results of the last five votes on draft international standards developed for the IVD industry (see Table I). The low number of U.S. IVD manufacturers that vote and submit comments on standards is surprising, considering the growing importance of international standards in the U.S., European, and other national regulatory systems. 

Anyone with a stake in the outcome of a standard may participate in the ISO standardization process. Documents are exchanged and comments are submitted over the Internet, so small IVD manufacturers with limited resources can participate. Nonetheless, even manufacturers that routinely send delegates and observers to attend working group meetings have neglected to vote and comment on draft standards. Either ISO TC212 is doing a very good job of producing IVD standards, or the process for channeling IVD industry input in the United States back to the technical committee is flawed. 

Several IVD manufacturers have revealed some interesting insights into why the latter might be the case. The most common reason is that a company’s delegates may not understand the ISO standardization process, so they miss the windows of opportunity to offer input. This article will explain how manufacturers can maximize the impact of their participation by understanding the process of developing international standards and its rules of engagement. 

Differences between the ISO and NCCLS Processes

Most TC212 participants are familiar with the NCCLS standardization process and assume that ISO operates the same way. On the surface, there are obvious similarities between the two organizations. For example, an ISO working group (WG) looks like an NCCLS area committee, and WG project teams look like area subcommittees. Moreover, the ultimate goal for both orga nizations is consensus. ISO defines consensus as “general agreement, characterized by the absence of sustained opposition to substantial issues by any important part of the concerned interests, and by a process that involves seeking to take into account the views of all parties concerned and to reconcile any conflicting arguments. Consensus need not imply unanimity.”¹

However, there are significant differences between the ISO and NCCLS standardization processes. This is due to the fact that the two organizations have fundamentally different objectives. NCCLS’s mission is to improve the quality of healthcare. ISO was formed to eliminate trade barriers between nations. 

The two organizations also have different constituencies that must reach consensus. NCCLS strives for a balanced participation among professional users, industry, and government sectors and seeks to achieve consensus among such groups that have a stake in the outcome. ISO focuses on reaching consensus among the national standards bodies that make up the ISO organization. Each country has one vote, and a balanced participation among users, industry, and government is not required. In fact, given ISO’s mission, it is not surprising that most participants in ISO working groups come from industry. 

In addition, the NCCLS and ISO processes for developing and achieving consensus standards are different. Attendance at NCCLS committee meetings is open, and the proceedings tend to be informal. Attendance at ISO meetings is restricted, and the proceedings are more controlled. Fortunately, ISO technical committees and their working groups have discretion over how they choose to operate.

How IVD Manufacturers Can Get Involved

IVD manufacturers that are interested in presenting their ideas and influencing draft standards can easily participate in the ISO standardization process. The following six steps will improve the effectiveness of their participation.

First, IVD manufacturers should join the U.S. technical advisory group (TAG) to TC212. This TAG is the entry point to ISO TC212, because countries, not companies, are ISO members. While the U.S. TAG is sponsored by NCCLS, membership in NCCLS is not required. A company can appoint to the TAG a delegate and an alternate, who may vote on draft standards and new work item proposals, offer comments, and receive announcements of TC212 and working group activities. 

Second, manufacturers should take a look at the current ISO TC212 work program and decide which projects are relevant to their products. Such information is available on the NCCLS Web site.² The TC212 business plan can be downloaded from the ISO Web site.³ While labeling and risk management standards will affect every IVD manufacturer, other product-specific ISO standards may also be of interest. For example, a standard for blood glucose meters was completed last year, and a standard for oral anticoagulation monitors is being developed.
 
Third, IVD manufacturers should identify in their organizations those technical experts who understand the subject matter and can evaluate proposed standards and requirements. Such experts should also be able to communicate credibly with their peers at other companies, and contribute to the ISO standardization process. 

Fourth, manufacturers’ delegates should study the ISO Directives, which are the rules that govern the process of developing international standards. The ISO Directives can be downloaded from the ISO Web site.^{4, 5} By studying these directives, a company’s delegates should be able to explain the ISO standardization process to their management. Otherwise, U.S. manufacturers will be at a disadvantage, since manufacturers in other countries that are experienced in the international standardization process know the directives well and always do their homework. 

Fifth, IVD manufacturers’ delegates and technical experts should participate actively in the U.S. TAG’s consensus process. Through the active participation of delegates and experts in the U.S. TAG, the U.S. positions on draft standards are developed. Because of the preponderance of U.S. manufacturers in the IVD industry, the U.S. TAG’s comments carry considerable weight in ISO working group deliberations. Consequently, the U.S. TAG’s positions are often adopted by other national delegations through the representatives from foreign subsidiaries of U.S. IVD companies. 

Table I. Summary of recent votes by U.S. IVD manufacturers on draft ISO TC212 standards (click to enlarge).

Sixth, manufacturers’ technical experts should volunteer to be on ISO working groups. Each country can send only a few delegates to attend working group meetings. However, the greatest opportunity to have an impact on the standardization process is at such meetings. If selected for a working group, delegates are expected to attend meetings, review documents, and contribute constructively to advance draft standards. 

The International Standardization Process

International standardization has two consensus stages. Final consensus on draft standards must be reached among all of the countries. Before that, the stakeholders in each country must first achieve consensus on a national position. In this regard, at least in principle, the U.S. TAG consensus process is similar to the balanced NCCLS process. Both organizations convene representatives of all stakeholders, who debate the proposed standards and requirements until a position emerges that everyone agrees with. 

Unfortunately, any resemblance to the NCCLS consensus process ends at the U.S. TAG. ISO working groups consist of delegates appointed by their national standards bodies, and their primary job is to represent their countries’ interests. Working group conveners cannot cross national borders to select specific experts or balance stakeholder participation. The appointed subject matter experts and delegates attend working group meetings only to the extent that their countries choose to send them. Of course, good working group conveners will identify the skill sets required for the group and will negotiate with national delegates to ensure the right expertise is brought into the standardization process. 

Developing ISO Standards

There are five distinct stages in the ISO standards development process. The title of a draft ISO standard includes a unique identification number, preceded by initials that indicate the progress made toward becoming an official ISO standard. 

New Work Item Proposal. Any ISO member country, liaison organization, or technical committee can propose a new work item (NWI). An NWI submitter is encouraged to include a draft of the proposed standard to jump-start the process. The project proposal must be approved by the TC212 membership, and at least five countries must volunteer to work on it. 

Working Draft. TC212’s working group 3 forms a project team to write an initial working draft (WD) of a standard. Several working drafts may be written before the working group is satisfied with the content. Most interim working drafts are distributed and reviewed via e-mail. WDs are developed and tracked within the working group, but do not have any special status in ISO. 

Committee Draft. The working group submits a draft standard to the TC212 membership for review and comment. At this committee draft (CD) stage, ISO expects the members to raise and resolve technical issues. Member countries are expected to invest the most time and effort at the CD stage. National experts should review the draft standard thoroughly, provide technical comments, propose specific changes, meet to address the comments, and work on achieving consensus on the next draft. U.S. IVD manufacturers have had a history of ignoring the CD stage, while raising concerns and attempting to introduce changes at later stages. This does not fit well with the ISO process, since significant changes can only occur at the CD stage. 

The ISO Directives emphasize the need to keep the process moving: 

National bodies need to ensure discipline with respect to deadlines and timetables in order to avoid long and uncertain periods of dead time. Similarly, to avoid rediscussion, national bodies have the responsibility of ensuring that their technical standpoint is established taking account of all interests concerned at the national level, and that this standpoint is made clear at an early stage of the work rather than, for example, at the final (approval) stage. Moreover, national bodies need to recognize that substantial comments introduced at meetings are counterproductive, since no opportunity is available for other delegations to carry out the necessary consultations at home, without which rapid achievement of consensus will be difficult.⁴

From this quote, it is important to recognize that revisions to draft standards are driven by the members’ comments submitted with their votes. At the CD stage, all comments must be addressed. However, to ensure that the working group will consider comments, they must raise a technical issue with a provision of the standard, propose a specific change to that section of the standard, and be accompanied by persuasive rationale. IVD manufacturers should realize that at the CD stage, hundreds of comments are generated, so it is important to give the working group succinct comments so that it can quickly evaluate and either accept or reject them. Philosophical statements, nonspecific requests for clarification, and questions are usually rejected without discussion. Member countries are expected to draw on their technical expertise and provide specific recommendations that the working group can address. 

If substantial changes are made to a CD, TC212 sends out the revised version as a second CD for another round of review, comment, and revision. 

Draft International Standard. Once TC212 agrees that the issues raised at the CD stage have been resolved, the next stage is the draft international standard (DIS). A DIS undergoes another review and vote by the TC212 membership, which includes 32 participating countries (P-members) and 16 observing countries (O-members). 

Four outcomes from the voting are possible. If a DIS passes with no dissenting votes, it may proceed directly to publication and skip the next voting stage. Therefore, if national delegates feel strongly about proposed changes to a DIS, they should cast a dissenting vote, or else their requests may be held until the next revision cycle. 

If dissenting votes are cast but the DIS meets the approval criteria, modifications are generally made to the DIS to address the dissenting votes before it proceeds to the next stage. The approval criteria require two-thirds of the P-members voting in favor and fewer than one-fourth of all P- and O-members voting against, excluding abstentions. 

If the approval criteria are not met, the standard is revised to address the objections, and another DIS vote is held. Alternatively, TC212 may decide to cancel the project. The expectation is that all technical issues should be resolved at the CD stage. Waiting until the DIS stage to raise new issues runs counter to the ISO Directives and often results in comments being deferred until the next revision. 

Final Draft International Standard (FDIS). At the final draft international standard (FDIS) stage, a standard is in the home stretch. The limitations on changes at the FDIS stage are even more drastic. At this stage, the vote is strictly for or against a standard. U.S. IVD manufacturers learned this lesson recently when their request to make last-minute changes to an FDIS was denied. Only corrections to errors introduced in preparing an FDIS are permitted. If an FDIS vote fails, the standard goes back to the CD or DIS stage, or the project is canceled. 

Once the FDIS vote is completed and the standard is approved, it will not be revisited again for five years, unless an interim revision is initiated earlier. 

Conclusion

The level of participation of U.S. IVD manufacturers in the international standardization process needs to increase. Input from the U.S. IVD industry is not getting into the comment-driven ISO process, leaving it to other countries to set the standards for the IVD industry. As international standards take on greater regulatory significance, the lack of participation by U.S. manufacturers can turn out to be a poor business decision. The simple steps outlined above will enable manufacturers to optimize their participation and help to ensure that the international standards meet the needs of the U.S. IVD industry. 

The second installment of this article will review the outcomes of the June 2004 ISO TC212 meeting in Utrecht, The Netherlands, and discuss the status of each of the ISO standardization projects of interest to the IVD industry. It will also explain the relationship of ISO to the European Committee for Standardization (CEN), the organization commissioned to produce the harmonized standards mandated by the IVD Directive. 

References

1. “Standardization and Related Activities — General Vocabulary,” ISO/IEC Guide 2:1996 (Geneva: International Organization for Standardization).

2. “ISO/TC212 Program of Work,” NCCLS Web site (Wayne, PA: NCCLS, 2004 [accessed 9 June 2004]); available from Internet: www.nccls.org/Template.cfm?Section=Program_of_Work.   

3. “Business Plan, ISO/TC212—Clinical Laboratory Testing and In Vitro Diagnostic Test Systems, Document N82,” International Organization for Standardization Web site (Geneva: ISO, 2001 [accessed 9 June 2004]); available from Internet: www.iso.ch/iso/en/stdsdevelopment/tc/tclist/TechnicalCommitteeDetailPage.TechnicalCommitteeDetail?COMMID=4643.   

4. “ISO/IEC Directives, Part 1—Procedures for the Technical Work,” American National Standards Institute Web site (Washington, DC: ANSI, 2001 [accessed 9 June 2004]); available from Internet: http://public.ansi.org/ansionline/Documents/Standards%20Activities/International%20Standardization/IEC/Procedures,%20Guides%20and%20Forms/Directives-Part1-Ed4.pdf.

5. “ISO/IEC Directives, Part 2—Rules for the Structure and Drafting of International Standards,” American National Standards Institute Web site (Washington, DC: ANSI, 2001 [accessed 9 June 2004]); available from Internet: http://public.ansi.org/ansionline/Documents/Standards%20Activities/International%20Standardization/IEC/Procedures,%20Guides%20and%20Forms/Directives-Part2-Ed4.pdf.  

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