CLSI eNews - 8 June 2005 (Plain Text Version)

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Milestone ISO/TC 212 Meeting in DC

How a Culture of Collaboration is Breeding Success for the Working Groups of ISO/TC 212

“A Pioneering Partnership”

It is 2002 and Technical Committee 210 of the International Organization for Standards (TC 212) needs help. The committee’s highly successful risk management standard, published with deficient guidelines on in vitro diagnostic (IVD) products, is up for revision. The guidelines need improvement, and improvement requires IVD expertise that TC 210 does not have. The committee does something it hasn’t done before. Like a neighbor in need, TC 210 calls on TC 212, Clinical laboratory testing and in vitro diagnostic test systems: can they borrow their IVD expertise?

TC 210 has called the right place. Klaus Stinshoff, PhD, Chair of TC 212, is eager to collaborate, and contacts ISO’s Central Secretariat himself for information: what is the procedure for partnership between two technical committees? The answer comes back: There is none.

Without applicable precedent for joint projects, the Central Secretariat suggests that TC 212 simply contribute the work, and allow it to remain under the official authorship of TC 210. But it is quickly surmised that the member countries that make up TC 212 will be unwilling to send delegates to do volunteer work outside of official TC 212 activities.

Stinshoff, also a member of CLSI's Board of Directors, suggests the IVD group develop an independent document that meets TC 210’s needs, and allow them to draw from it for their document. But a political stumbling block arises: TC 210’s document has already been recognized by the European Union (EU) as a European harmonized standard. Gaining for a separate IVD risk management standard the same EU recognition that ISO 14971 has already received will be an arduous process, requiring lengthy negotiations and consuming the committee’s resources.

Just as helping out a neighbor begins to seem impossible, TC 212 finds a solution:
If the group works on the document through its normal process—stopping at the point of publication to hand it over for use in ISO 14971—their work will simultaneously meet the criteria for official TC 212 activity, fulfill the needs of TC 210, and, as an official part of 14971, become part of a recognized standard. A bonus.

“There are often pragmatic reasons,” says Donald M Powers, MD, Convenor of TC 212 Working Group 3, “why some things are done in the interest of global harmonization.”

But this partnership, born of simple altruism and down-to-earth collegiality, carries a significance that goes beyond the IVD standard.

“This particular sort of partnership is new,” Stinshoff says. “It’s a pioneering partnership: we are breaking ground as to how groups within the ISO organization can work together in a positive way.”

Pragmatic or idealistic, in the decade since its inception, TC 212’s culture of scientific collaboration and intercultural compromise have become as dominant a characteristic as the committee’s collective area of expertise in IVDs and the clinical laboratory. And there might be a connection: in Washington, DC, last month, in the committee’s tenth anniversary year, repeatedly manifested in projects, initiatives, and accomplishments was the committee’s high valuation of partnership and cooperation—among its own working groups, and among its individual members; with other ISO technical committees, and with outside organizations; with the different sectors of its global constituency, and even with the users of the standards TC 212 develops.

The punchline for cynics? All of this professional cooperation is leading to some landmark—maybe even historic—achievements for the healthcare world.

“Intense Discussions”

The TC 212 Secretariat is administered by the Clinical and Laboratory Standards Institute (CLSI), which, together with the American National Standards Institute (ANSI), played a key role in the founding of TC 212 in 1995, by presenting to ISO the need in the laboratory field, which would form the basis of the committee’s scope: “Standardization and guidance in the field of laboratory medicine and in vitro diagnostic test systems,” including “quality management, pre- and post-analytical procedures, analytical performance, laboratory safety, reference systems and quality assurance.”

With 20 participating member nations on TC 212 at the time of its first meeting, the committee’s participating membership has broadened to 32 in the past decade, along with 16 observer countries. TC 212 spans all corners of the earth, drawing nations as geographically, socio-politically, and culturally disparate as Chile, Jamaica, Iran, Norway, and Korea together in collaboration on four working groups (WG):

* Quality and competence in the clinical laboratory (WG 1)
* Reference systems (WG2)
* In vitro diagnostic products (WG3), and
* Antimicrobial susceptibility testing (WG4)

Among TC 212’s flagship documents is Medical laboratories – Particular requirements for quality and competence (ISO 15189), authored by Working Group 1 (WG1). The standard took popular quality management and assurance standard ISO 9000 and used it to develop something specific and new: a standard for the medical laboratory. However, as ISO 15189 was being prepared for publication, a conflict developed that would take years to resolve.

CASCO, ISO’s Committee on conformity assessment, had authored ISO 17025, General requirements for the competence of testing and calibration laboratories, also based on the ISO 9000 standards. It appeared to CASCO that, after they had invested the time, energy, and intellectual property into developing ISO 17025, TC 212 was developing a competing standard.

During the development period of ISO 15189, and beyond, TC 212, CASCO, and TC 176, creator of the ISO 9000 series, engaged in a number of what Ireland’s Desmond Kenny, FRCPath, Convenor of WG1, calls “intense discussions.”

Kenny explains the misunderstanding:

“Their view was, ‘Why should medical laboratories have a document other than ISO 9001:2000, which (covers) all industries and all activities?’”

“Now, in fact,” says Kenny, “the big difference is that 15189 isn’t just about quality management; it’s also about competence. And competence is the key word when it comes to laboratory accreditation.”

The deliberations between the two groups were heated and ongoing, and Kenny says it ultimately took a pact to quell the enmity between them: with ISO 15189 and ISO 17025 on parallel schedules for revisions, each committee has agreed to make “parallel changes” with one another, in order to keep each standard aligned with the other.

As part of the new system of transparency between the two groups, TC 212 WG1 and CASCO have also agreed to send a representative to one another’s meetings. The WG1 meeting in Washington, D.C. was the first at which a member of CASCO (John McDonald of England) was present.

“He sat in on the Working Group 1 meeting for the whole duration,” Kenny says. “It was actually quite valuable to have him there, because we were able to check with him on whether CASCO would be happy with this or that.”

McDonald concurs: “I think the mood was very good. There certainly were difficulties in the past, but that’s behind us. We are looking forward on our side to a full revision of 17025, and on (the TC 212 WG1) side, likewise. And these two things should proceed in parallel. I’m sure there will be a dialogue over the next year, and I’m confident that we will end up with a matched pair of standards that don’t interfere with one another.”

“I think that we’ve learned from our experiences,” Kenny says. “We really were not in good enough communication with bodies like CASCO, and this caused a certain amount of misunderstanding.”

“Double perspective”

In preparation for the extensive revision of the ISO 15189 document, Working Group 1 (WG1) has taken the unusual step of reaching out to the users of the standard, in medical laboratories around the world, asking them for feedback on the document via a special “stakeholders survey.” Recommended as a joint initiative by ISO and the International Laboratory Accreditation Cooperation (ILAC), the survey is designed to harness the broad popularity of the document itself as a means of gaining input from globally diverse perspectives.

Heading up the project is CLSI Quality Systems volunteer Regina Robertson, who, as Technical Manager at Australia’s National Association of Testing Authorities—an accreditation body of ILAC—carries the unique “double perspective” of both medical laboratory and accreditation body.

“The National Association of Testing Authorities in Australia has really close contact with the people who are using 15189 at the laboratory level. And of course we also need to use it at the accreditation level. I have a perspective on both sides: one is how it affects labs; the other, how it affects us as an accreditation body.”

The survey was sent via e-mail to 100 laboratories in “all corners of the globe,” Robertson says, asking about problems with understanding, coverage, and clarity; conflicts between 15189 specifications and normal practices or regulations; and resource deficiencies that make carrying out the standard impossible. To date, Robertson has received a response of nearly 50%, and counting.

“It appears to have really struck a chord in the medical arena,” Robertson says. “And, up to now, there have been a lot of different practices around the world. This seems to be a real opportunity for the different players in the medical arena to actually talk to each other on an international level. People are coming back and saying it’s a wonderful opportunity to harmonize practice around the world.”

Robertson says that, with tight budgets for ISO, ILAC, and their member organizations, such innovative methods of gaining global feedback are becoming increasingly essential to the improvement of standards.

“I don’t think any of us has the sort of money to put into a fund and say, ‘All right, let’s get experts on this subject from different parts of the world together to talk about this subject.’ There’s nothing obvious that provides a venue for everyone to come together who might want to come together. But we need to take a look at what we can do to facilitate and to assist. And that was really the main aim of the survey.”

Making up a substantial part of survey feedback, Robertson says, are problems related to traceability and measurement uncertainty—interconnected but uniquely complex areas which TC 212 WG2 is working to address. Following a consensus in Washington that attention is needed to the topic of measurement uncertainty for medical laboratories, WG2 Convener Rene Dybkaer, MD, began to form a working subgroup, beginning the long process of developing a standard on the notoriously difficult topic.

“This is a considerable problem to attack for many laboratories in the hospitals,” Dybkaer says, “especially because they do not have the necessary data in all cases.”

Dybkaer—who is also contributing his expertise to the CLSI document, Expression of Uncertainty of Measurement—explains that discrepancies exist between the types of measurements needed in the exigency of the day-to-day medical laboratory and the acutely detailed sources they rely upon for measurement information, such as the Guide to the Expression of Uncertainty in Measurement (GUM). With sources like GUM specifying measurement procedures at a level of complexity for which the hospital laboratory neither has time nor medical need, laboratorians are seeking a method for measuring the uncertainty of their results that is practical and directly applicable to their work environment.

“We can harmonize”

Regulatory agencies and industry have long held in common a central concern with two major areas: quality management and risk management. Stinshoff notes that these two elements stand out as being of fundamental importance to the regulatory authorities of the developing world, from the European Union to the Ministry of Health in Japan, to the U.S. FDA to Health Canada. While regulators in recent years have moved away from prescribing detailed methods of design and manufacture, leaving the responsibility with the manufacturer, the same standards of design and manufacture remain both necessary and expected. There is a resultant need, Stinshoff explains, for increased connectivity between the two sectors, so standards are upheld.

Enter Working Group 3 (WG3), which, along with its work on the IVD part of the risk management standard, is developing two more projects that bring together the manufacturing and regulatory sectors. The first is the subgroup developing an international standard for manufacturers on the labeling of in vitro diagnostic products. Headed up by CLSI volunteer Kay Setzer, the subgroup includes labeling experts from around the world, including both the very IVD manufacturers who will be affected by the standard and representatives from national regulatory bodies who are monitoring the work.

“It’s really a document for use by manufacturers with the regulatory agencies,” Setzer says. “And we are well represented by both groups.”

Setzer’s subgroup was formed when ISO received a work item proposal calling for ISO to adopt the IVD labeling standards of the Comité Européen de Normalisation (CEN). ISO leaders decided that a more international basis should be considered for the standard. With technical report 18112, In vitro diagnostic medical devices – Information supplied by the manufacturer, TC 212 did a study of major regulations around the world, drawing the conclusion that ISO standards were necessary.

However, says WG3 Convener Donald M. Powers, PhD, the subgroup faced an early obstacle in the skepticism of peers.

“Several people were initially pessimistic about whether TC 212 could develop a viable international labeling standard, because labeling requirements are defined by regulations, and many were thought to be conflicting or incompatible.”

But Setzer and Powers describe the process of identifying those differences—conflicting regulations involving language, symbols, and exemptions—as a necessary errand in their larger mission of harmonization.

“Our intent was to identify those areas that were different,” Powers says. “And if we couldn’t address them through a standard, then we would at least highlight them, so organizations like the Global Harmonization Task Force could try to convince the countries to change their requirements. The first thing we needed to do was make people aware of what the differences were, and maybe we could give them some proposed solutions. One disclaimer we added to the standards is that local regulatory requirements will trump the standard. We had hoped to deal with maybe 80% of the requirements, but I think it’s turned out that we have dealt with closer to 95 to 98%.”

“More and more countries throughout the world are becoming regulated,” says Setzer. “And as each one becomes regulated, they have to start over from scratch with the question, what is it they want on labeling for an IVD? Instead of doing that, and everybody coming up with something just a little different, if we can all adopt the ISO standards, then we can harmonize and eliminate some of the trade barriers.”

“Ease their path”

“I haven’t been involved with ISO very long,” says Working Group 4 Convener James H. Jorgensen, PhD. “It’s sort of new wilderness for me.”

Which may not make much of a difference, considering that all of WG4 is navigating unfamiliar territory at the moment, embarking on a partnership with a working group from the European Committee for Standardization (CEN).

“There’s very little administrative direction,” Jorgensen says. “There’s no real provision for the two committees working absolutely together as one big group. But, it turns out, in this case, there has been some efficiency, and, through collegiality between the two groups, it has been possible to meet at the same time, and to have input from both groups simultaneously.”

The two standards in development by WG4 and CEN/TC 140 are 20776-1 and 20776-2, two antibiotic susceptibility projects initially proposed by CEN. When TC 212 decided that the documents should be global projects, an agreement was made between ISO and CEN that the two bodies would work together under the terms of the Vienna Agreements, an accord established 30 years ago in the interest of avoiding duplication of effort.

Under the agreement, CEN has taken the lead in work on both documents, with ISO serving, Jorgensen says, in more of an editorial capacity. However, the two groups share the same voting period and privileges, and the document itself is published as an ISO document.

With WG4 and CEN/TC 140 meeting for the first time in Spring of 2004, their first project, Reference method for in vitro testing of the susceptibility of antimicrobial agents against bacteria involved in infectious diseases (20776-1), has seen a lightning-fast development process, with the document’s first draft vote having concluded 6 June 2005.

“For the first time, there has been an effort to create a true global standard reference method for antibody testing, (with) which there has been some give-and-take between the Europeans and the North Americans in particular. So there has been an opportunity here to harmonize the way things are done.”

The working subgroup on 20776-2 is largely made up of diagnostic manufacturers looking to develop a standard that will fill the void that exists in many European countries that do not have a uniform set of standards upon which definitions of acceptable performance of antibiotic susceptibility testing can be based, thus stymieing industry leaders looking to expand across borders.

“In Europe now, countries may require, or may not require anything, and there’s not been a uniform set of standards—not like we have with the FDA. I think that (with the 20776-2) a company can go to a country, let’s say Italy, or Spain or someplace, and say, ‘We want permission to sell our device in your country, and we meet the ISO standards for performance.’ And that should then ease their path for registration in that country.”

“It has to lead to success”

In discussing the future, Stinshoff expresses eagerness to see a proposal by Working Group 3 to partner with Working Group 1 on the development of a document to bring risk management to the laboratory.

“Risk management really should be as important for laboratories as it is for manufacturers. A closer cooperation in standard-setting between manufacturers and laboratories. I think this is something that will become one of the major emphases of TC 212 in the future: that laboratories and manufacturers to work together in setting standards. Difficult, but it has to lead to success.”

Powers is at the helm of the proposal, which he says, at this point, is in WG1’s court.

“We need a system where the manufacturer does its part, and then the laboratory takes responsibility for its part. That partnership doesn’t exist today.”

Powers also says he’d like to begin more dialogue with the Global Harmonization Task force, in a liaison capacity, to avoid effort duplication and share knowledge.

With the results still coming in for WG1’s stakeholder’s survey, Robertson is hoping that the breadth of response to the survey will set a wider context for participation in the future, especially on the part of developing countries.

“Our challenge is to make use of what appears to be a very high level of interest. We’ve really made contact with the stakeholders of the standard. It certainly appears to be having an effect on harmonization—at least it’s begun the process of thinking about it, which is much more than we had before.”