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CHAPTER 34

Standards and Regulatory


Considerations
Michael B. Jaffe David G. Osborn

CHAPTER OUTLINE
What Is a Standard?

Pending Regulatory Changes in the United


States

REGULATION OF MEDICAL DEVICES

MEDICAL DEVICE VOLUNTARY STANDARDS

OVERVIEW

Global Harmonization Task Force


Medical Device Regulation in the United
States
Definition of Terms
Medical Device Regulation in the European
Union
Medical Device Regulation in Japan
Medical Device Regulation in China

ROLE OF STANDARDS IN MEDICAL DEVICE


REGULATION
Early Efforts in the United States
Food and Drug Administration
History
Organization of the Food and Drug
Administration
Classification of Devices
Europe
United States
Classifying a Device in the United States
Premarket and Placing-on-Market Processes

OVERVIEW
It was once possible to practice safe and modern
anesthesia without any knowledge of the regulatory and
voluntary standards governing anesthesia equipment
and practice. This has changed, however, and individual
practitioners are now subject to federal and state regulations regarding the use of these devices and are strongly
influenced by international standards and agreements.
The arena of medical device standards and regulations is
complex and arcane, and there is much overlap of
authority. This chapter reviews the history, present status, interested parties, relevant standards, standards
processes, and pending developments that will affect the
clinician in the future. The reader should be left with a
good understanding of both the processes and the interested parties in the constantly evolving international
setting of standards and regulations.

Overview
Stages in the Development of International
Standards
Organization of Standards Development
Organizations
U.S. Standards Development Organizations
of Interest
American National Standards Institute (ANSI)
ASTM International
Association for the Advancement of Medical
Instrumentation (AAMI)
National Fire Protection Association (NFPA)
Institute of Electrical and Electronics
Engineers (IEEE)
Medical Device Standards
The General Standard (60601-1)
Standards of Particular Interest
Other Standards and Changes
Interoperability
Small-Bore Connectors
Alarm Systems

What Is a Standard?
A standard is a document, established by consensus and
approved by a recognized body, that provides for common and repeated use, rules, guidelines, or characteristics
for activities or their results, aimed at the achievement of
the optimum degree of order in a given context.1 Standards should be based on the consolidated results of science, technology, and experience, and they should be
aimed at the promotion of optimum community benefits.
In reality, a standard is an agreed restriction for a common good and a shared benefit.1

REGULATION OF MEDICAL DEVICES


The rules governing medical devices differ throughout the
world.2 Many different models exist, such as the U.S. Food
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PART VII Safety, Standards, and Quality

and Drug Administration (FDA), European Union (EU)


CE-marking system, and various registrations, listings,
licenses, and approvals in other countries. Efforts have been
under way since the early 1990s via organizations such as the
Global Harmonization Task Force (GHTF) to better
achieve uniformity among national medical device regulatory
systems around the world. This is being done with two aims
in mind: enhancing patient safety and increasing access to
safe, effective, and clinically beneficial medical technologies.

Global Harmonization Task Force


A partnership between regulatory authorities and regulated
industry, the GHTF consisted of five founding members:
the European Union, United States, Canada, Australia, and
Japan. The GHTF intended to foster international harmonization in the regulation of medical devices by the development of a regulatory model and supporting documents to
underpin globally harmonized regulation of medical technologies. Regulatory and industry representatives from
Europe, the Asia-Pacific region, and North America were
encouraged to collaborate and actively participate in the
development of guidance documents that describe regulatory practices to ensure the safety, effectiveness, and quality
of medical devices. This task has been substantially completed, the GHTF has published many final documents on
their Web site, and some countries have based their newly
developed regulatory processes on these documents. Notwithstanding this success, little progress has been made by
the founding members of the GHTF in the harmonization
of their regulatory processes to this model. Many other
countries, particularly some of the BRIC countriesBrazil,
Russia, India, and Chinaunsuccessfully attempted to join
the GHTF.
The FDA proposed, and the five founding members
agreed, that the time had come to dissolve the GHTF and
create a new, regulator-only forum with global reach that
would consult with other interested groupsincluding
industry, health care professionals, and consumersin the
advancement of regulatory harmonization. In October
2011, the regulatory authorities of Australia, Brazil, Canada, China, the European Union, Japan, and the United
States and the World Health Organization (WHO)
announced the establishment of the International Medical
Device Regulators Forum (IMDRF) to replace the GHTF.
The IMDRF intends to provide guidance on strategies,
policies, directions, and activities to accelerate international
medical device regulatory harmonization. Unlike the
GHTF, various stakeholder groups, such as industry, academia, health care professionals, and consumer and patient
groups, are no longer invited to participate in the steering
committee or management committee, although they can
be invited to participate in ad hoc working groups.

Medical Device Regulation in the United


States
Manufacturers of medical devices distributed in the
United States must comply with certain basic regulatory
requirements:
Establishment registration
Quality Systems (QS) regulation

Labeling requirements
Premarket Notification 510(k), unless exempt, or
Premarket Approval (PMA)
Medical device listing
Medical Device Reporting (MDR)
Definition of Terms
Establishment Registration. A manufacturer must file
its name and all places of business with the FDA. Any
additional place of business must be registered immediately. Registration is performed electronically.
Quality System Regulation. The QS regulation requires
the manufacturer to have a written quality system that is
subject to periodic audit by the FDA. The QS regulation
requires every medical device to be designed, manufactured, packed, stored, and installed in conformity with
current Good Manufacturing Practices (GMP). The QS
regulation requires use of design validation, investigation
of complaints, and a corrective and preventive action plan
to identify root causes of product nonconformance with
standards and specifications and to implement effective
actions to prevent recurrence.
Labeling Requirements. Medical devices must be
labeled either on the medical device or on its immediate
container. The label must identify the company name,
trade name, or trade symbol of the manufacturer as well
as the name and place of business of the manufacturer,
packager, or distributor and the identity of and quantity
of the contents of the package. In addition, the labeling of
a medical device must provide adequate directions for use
and adequate warnings against unsafe use for a layperson,
unless the medical device is a prescription medical device,
in which case the labeling may be written for health care
professionals. The labeling of a prescription medical
device may be made available electronically.
Premarket Notification 510(k). The 510(k) process is
designed to ensure, through a quality review process,
that marketed medical devices, subject to general and
applicable special controls, provide a reasonable assurance of safety and effectiveness. It is also designed to
foster innovation. This is achieved by comparing the
(new) device to an existing (predicate) moderate-risk
medical device and demonstrating that the new medical
device is substantially equivalent to the predicate. The
510(k) process applies to moderate-risk medical devices
(typically class II; Table 34-1).
Premarket Approval. The premarket approval (PMA)
process is designed to ensure that a specific marketed
medical device provides a reasonable assurance of safety
and effectiveness through a scientific review process of
safety and effectiveness data (clinical trials). The PMA
process applies to novel medical devices or new high-risk
medical devices (typically class III; see Table 34-1).
Medical Device Listings. A manufacturer must file a list
identifying each medical device made or processed for
commercial distribution in the United States and its

34 Standards and Regulatory Considerations

695

TABLE 34-1 Comparison of FDA 510(k) Premarket Notification and Premarket Approval
Factor

510(k) Premarket Notification

Premarket Approval

Classes of devices
Number annually
Documentation (length)

Class I and II devices


2428*
Depends on type of submission
(special, traditional)
Typically 50 to 250 pages
Reasonable assurance of safety and effectiveness

Class III devices


24*
Typically thousands of pages

Regulatory requirement
Evidence
Clinical studies provided?
Review period (goal/typical)
Source of required
information
Outside review?
User fees

Substantial equivalence: comparison to an


existing predicate medical device
Varies depending on device type, overall about
10% with clinical studies
90/120 days (traditionally 74% of submissions)
Average time for anesthesiology branch: 140 days
21 CFR 807.87
No
$4717

Reasonable assurance of safety and


effectiveness
Scientific review process of safety and
effectiveness data
Required for both safety and
effectiveness
180/410 days
Section 515(c)(1) of the federal Food,
Drug, and Cosmetic Act
FDA Advisory Panel meeting
$220,050
Additional changes made via PMA
supplements

*2011 actual.
An analysis of FDA 510(k) data from 2006 to 2010, Emergo Group (January 9, 2012).
Three-year average, fiscal years 2006 to 2008.
2012 actual.
CFR, Code of Federal Regulations; FDA, Food and Drug Administration; PMA, Premarket Approval.

labels and labeling. Additionally, the manufacturer must


provide a notice of discontinuance once a medical device
is no longer made. Listing is performed electronically.
Medical Device Reporting. Manufacturers of moderateand high-risk medical devices (class II or class III) must
report to the FDA when they learn of information that
reasonably suggests that a medical device has or may have
caused or contributed to the death or serious illness of or
serious injury to a patient, or when they learn of an event
that might contribute to the death or serious illness of or
serious injury to a patient should it reoccur.

Medical Device Regulation in the


European Union
In the EU, medical devices are regulated by one of three
directives: the Medical Devices Directive (MDD), the
Active Implantable Medical Devices Directive (AIMDD),
or the In Vitro Diagnostic Directive (IVDD). Directives
are an instrument from the European Parliament directing each member state to enact a law that embodies the
content of the directive. The directives establish the regulatory scheme based on a risk-based classification system
and, for higher risk devices, a certified quality system.
The directives establish broad safety and performance
criteria called the Essential Requirements (ERs). All medical devices are required to demonstrate compliance with
the ERs.

Medical Device Regulation in Japan


The Pharmaceutical Affairs Law (PAL) applies to all medical devices in Japan. PAL is controlled by the Ministry of

Health, Labor, and Welfare (MHLW). All medical


devices are classified with a Japanese classification rule
that was basically an adopted GHTF rule. Based on the
classification, a medical device can require notification, certification, or approval (respectively, from lower to higher
risk and from lower to higher effort). Additionally, certain
measuring devices require a separate metrological (pattern) approval.

Medical Device Regulation in China


The State Food and Drug Administration (SFDA) is the
central government agency in charge of drug and medical
device administration with functions similar to those of
the FDA in the United States. All medical devices must
be registered with the SFDA before they are exported to
or sold in China. The SFDA process requires in-country
testing of medical devices for the Chinese market. Additionally, certain measuring devices require a separate
metrological approval.
The General Administration of Quality Supervision,
Inspection, and Quarantine (AQSIQ) is tasked with oversight, inspection, and quarantine as well as with establishing the technical standards for imported and exported
goods. AQSIQ maintains responsibility for certifying
electrical safety for a wide variety of products with the
so-called China Compulsory Certificate (CCC). The
CCC safety license process requires manufacturers to
obtain the CCC mark before exporting or selling products listed in the CCC catalog into the Chinese market.
The CCC mark is administered by the Certification and
Accreditation Administration (CNCA). The China Quality Certification Centre (CQC) is designated by the
CNCA to process CCC mark applications. Electrical

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PART VII Safety, Standards, and Quality

medical devices require CCC certification prior to SFDA


registration.

ROLE OF STANDARDS IN MEDICAL


DEVICE REGULATION
In almost all jurisdictions, standards are used for the
detailed requirements used to regulate medical devices,
and regulations are used to set the high-level principles.
The exception is China, where the standards are written
into the law and become part of the regulation.
The U.S. FDA reviews standards and, when found
appropriate, recognizes them as suitable by publishing
them in the Federal Register (FR). Manufacturers may
then use those standards to simplify regulatory submissions. The EU harmonizes standards that they find
acceptable by publishing them in the Official Journal (OJ).
A harmonized standard has a special status. Medical
devices that comply with the relevant harmonized standards are presumed to demonstrate compliance with the
relevant essential requirements, and this presumption
cannot be easily challenged.

Early Efforts in the United States


The passage of the Federal Food, Drug, and Cosmetic
Act (FD&C Act) of 1938 was hastened by a tragedy the
previous year in which nearly a hundred people died after
ingesting Elixir Sulfanilamide.3 This act included new
provisions to:
Extend control to cosmetics and therapeutic medical devices
Start a new system of drug regulation that requires
new drugs to be shown to be safe
Loosen misbranding requirements by eliminating
the need to prove intent to defraud
Ensure that safe limits be created for unavoidable
poisonous substances
Authorize food standards created for identity, quality, and container filling
Authorize medical device factory inspections
Add the remedy of court injunctions against violative manufacturers
Increasing public concern over the safety and effectiveness of medical devices in the late 1960s and early
1970s led to the formation of a study group within the
Department of Health, Education, and Welfare, the

1976
Medical Device
Amendments

1990
Safe Medical
Devices Act

1993
MedWatch
launched

predecessor of the present Department of Health and


Human Services (DHHS). This study group, chaired by
Dr. Theodore Cooper of the National Heart, Lung, and
Blood Institute, estimated, as did other studies at the
time, that over the previous decade more than 10,000
injuries and hundreds of deaths were linked to medical
devices still on the market.4
Recommendations from this study group formed the
basis of the Medical Device Amendments of 1976. The
members of the group felt that performance standards
would be more effective than a PMA in ensuring the
safety and effectiveness of most new medical devices.
Since 1976, the FDA and medical device regulation has
evolved. A timeline showing significant events since 1976
is shown in Figure 34-1.

Food and Drug Administration


History
The Food and Drug Administration is a scientific, regulatory, public health agency whose mission is to protect and
promote public health. One of its purposes is to establish
a reasonable assurance of the safety and effectiveness of
medical devices marketed in the United States. Regulation of medical devices in the United States by the FDA
has been undergoing an evolution since the passage of the
Medical Device Amendments in 1976. This evolution (see
Fig. 34-1) has included the passage of several pieces of
legislation and the establishment of important reporting
and disclosure tools, such as MedWatch (www.fda.gov/Sa
fety/MedWatch/ucm170520.htm) and ClinicalTrials.gov.
The meaning of the terms safety and effectiveness is dependent on the risk profile of the medical device. For low-risk
medical devices (class I), general postmarketing controls are
considered sufficient to provide reasonable assurances of
safety and effectiveness. For moderate-risk devices (class II)
for which there is sufficient information, so-called special
controlstypically a combination of standards and guidance
documentsare considered sufficient to provide reasonable assurances of safety and effectiveness. For high-risk
devices (class III) or for those medical devices on which
there is not sufficient information, scientific evidence from
well-controlled clinical trials is required to provide reasonable assurances of safety and effectiveness.
Medical Device Amendments of 1976. In 1976, the Medical Device Amendments (21 U.S.C. Secs. 513 through 521)
1999
2002
ClinicalTrials.gov
Medical Device User Fee
founded
and Modernization Act
1997
Office of Combination
Food and Drug Administration
Products formed
Modernization Act

1976

2010
FIGURE 34-1 n Timeline of Food and Drug Administrationrelated medical device legislation since 1976.

34 Standards and Regulatory Considerations

supplemented the original Federal FD&C Act, which


required a reasonable assurance of safety and effectiveness
before a medical device can be marketed. Section 201(h) of
the FD&C Act defined a medical device as:
An instrument, apparatus, implement, machine, contrivance, implant, invitro reagent, or other similar or related
article including any component, part or accessory which is
(1) recognized in the official National Formulary, or the
United States Pharmacopoeia, or any supplement to them,
(2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (3) intended
to affect the structure of the body in man or other animals
and which does not achieve any of its principal intended
purposes through chemical action within or on the body of
man or other animal and which is not dependent upon being metabolized for the achievement of any of its principal
intended purposes.
These amendments provided the FDA with the
authority to regulate medical devices by establishing a
three-tiered system of regulation. Manufacturers were
required, at the very least, to register with the FDA any
new low-risk device. High-risk devices, on the other
hand, required PMA, and moderate-risk devices required
PMN and FDA clearance prior to being marketed. In all
cases, however, the FDA was required to conduct postmarket surveillance of devices after introduction into
clinical use, and manufacturers were required to report
significant incidents to the FDA.
After the 1976 amendments, problems with an anesthesia machine that led to the death of four patients
exposed problems with the regulatory framework in place
at that time. This led to congressional hearings and
helped lead to the MDR regulations, issued shortly thereafter, which required all manufacturers and distributors
of medical devices to report deaths and serious injuries
from medical devices to the FDA.5 During those hearings, the FDA agreed to work to minimize the dangerous
use of medical devices, and real efforts for extending the
FDAs Good Manufacturing Practices to cover the design
of medical devices began.
A series of legislative changes have been made by Congress to the FD&C Act. They include:
Safe Medical Devices Act (SMDA) of 1990
Medical Device Amendments of 1992
FDA Modernization Act (FDAMA) of 1997
Medical Device User Fee and Modernization Act
(MDUFMA) of 2002
Safe Medical Devices Act. The Safe Medical Devices
Act (SMDA) was signed into law on November 28, 1990
(Public Law 101-629).6 Elements of the new law included
user reporting of probable device-related issues, distributor/manufacturer reporting of device incidents,
changes to the 510(k) clearance and PMA processes,
changes to the classification of devices, and changes to
the FDAs internal performance standards process, recall
authority, postmarket surveillance, and greater enforcement powers. One of the most important features of this
law is that it imposed mandatory requirements on

697

facilities that use medical devices. The user shared the


onus, which previously only had fallen to the manufacturer. Thus the FDA has gained some regulatory access
and control in the local hospital. With this new law, the
emphasis was supposed to have been moved from premarket review to postmarket surveillance. Consistent
with this change in philosophy, the processes by which
devices are classified and approved were to have been
relaxed. There is little evidence that this has happened.
All institutionsfrom major medical centers to small,
freestanding ambulatory surgical centersare now
expected to report any information on the death or
injury of a patient that may have been caused by a medical device. Both the FDA and the manufacturer must be
notified within a specified period of time and in a prescribed manner. In addition, institutions are required to
produce biannual reports summarizing all individual
reports filed over the past 180 days.
The SMDA made important changes in the law compared with the 1976 Medical Device Amendments,
including certain changes in the requirements for all
classes of medical devices. The Medical Device Amendments of 1992 were intended to clarify both the Medical
Device Amendments of 1976 and the SMDA.
It is interesting to note that within the medical industry, medical devices are now subject to more stringent
regulation than is the pharmaceutical industry. This is
the case despite the fact that most of the recent congressional investigations and public scandals have been associated with pharmaceuticals.
MedWatch. The act causes the FDA to consolidate several adverse reaction reporting systems under the name
MedWatch. The program is designed to provide a single
portal for health professionals for the voluntary reporting
of problems associated with medical devices. In this program, the FDA partners with a wide variety of organizations, which are encouraged to play an active role in
postmarketing surveillance.
Food and Drug Administration Modernization Act
(FDAMA) of 1997. The FDAMA included provisions
that require the FDA to accelerate review of devices. In
response the FDA completed dozens of guidance documents, most of which added requirements for manufacturers. FDAMA included a mandate that the Center for
Devices and Radiological Health (CDRH) create a standards program, which has been very successful. FDAMA
included provisions for regulation of advertising of unapproved uses of drugs and devices as well as regulation of
health claims for foods.
Medical Device User Fee and Modernization Act
(MDUFMA) of 2002. The MDUFMA included provisions that permit the FDA to assess fees from sponsors of
medical device applications for evaluation. In return the
FDA agrees to improve performance to certain goals.
MDUFMA included provisions for device establishment
inspections by accredited third parties, and new requirements emerged for reprocessed single-use devices.
MDUFMA also included provisions that led to the formation of the Office of Combination Products within the

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PART VII Safety, Standards, and Quality

Office of the Commissioner to oversee review of products that fall into multiple jurisdictions within the FDA.
An excellent review of the regulatory history of the FDA
may be found in Section 2 of the recent Institute of Medicine (IOM) report.7 In late 2012, the MDUFMA was
reauthorized for an additional 5 years. This reauthorization includes numerous incremental improvements to the
device approval process.
Organization of the Food and Drug
Administration
The FDA is an agency within the DHHS. It consists of
the following centers and offices:
Office of the Commissioner
National Center for Toxicological Research
Office of Operations
Center for Veterinary Medicine
Office of Medical Products and Tobacco
Center for Devices and Radiological Health (CDRH)
Center for Biologics Evaluation and Research
(CBER)
Center for Drug Evaluation and Research (CDER)
Center for Food Safety and Applied Nutrition
Center for Tobacco Products
Office of Regulatory Affairs
The parts of the FDA of most interest to anesthesiologists include the CDRH (devices), CDER (drugs), and
CBER (biologics/vaccines, gene therapies). The discussion will focus on the CDRH and its activities.
Center for Devices and Radiological Health. In 1982,
the FDA established the CDRH, which was formed from
elements of the old Bureau of Medical Devices and the
Bureau of Radiological Health. The CDRH has evolved
over the past 30 years and now has seven divisions, or
offices, that report to the Directors Office: 1) Compliance, 2) Management Operations, 3) in Vitro Diagnostic
Device Evaluation and Safety; 4) Surveillance and Biometrics, 5) Communication, Education, and Radiation
Programs, 6) Science and Engineering Laboratories, and
7) Device Evaluation.
The Office of Device Evaluation (ODE) is responsible
for the program areas through which medical devices are
evaluated or cleared for clinical trials and marketing. These
programs include PMA, product development protocol,
humanitarian device exemption, investigational device
exemption, and premarket notification programs. The
ODE is presently divided into five scientific divisions:
1. Anesthesiology, General Hospital, Infection Control, and Dental Devices
2. Cardiovascular Devices
3. Reproductive, Gastro-Renal, and Urological Devices
4. Ophthalmic, Neurological, and ENT Devices
5. Surgical, Orthopedic, and Restorative Devices
Each division is further subdivided. The Anesthesiology, General Hospital, Infection Control, and Dental
Devices division is divided into four branches, each with
a separate branch chief.
Medical Devices Advisory Committee. The 1976
amendments also established the Medical Devices Advisory

Committee, which currently consists of 18 medical device


advisory panels that range from immunology to radiology
for the purpose of advising the FDA on issues related to the
safety and effectiveness of medical devices. These advisory
panels include the Anesthesiology and Respiratory Therapy Devices Panel. Each panel has nine members in addition to an FDA employee, who serves as the executive
secretary. Seven of the panelists are voting members, and
the consumer and industry representatives are nonvoting
members. A panel can request consultants when necessary.
In 2010, the FDA changed the procedures of the medical device advisory panels. The panels are no longer
being asked to vote on whether to recommend a medical
devices approval or conditions of approval. Instead, they
are being asked to vote on the devices safety and effectiveness and how the devices benefits compare with its
risks. Typically, each of these attributes is voted separately with questions phrased along the lines of:
1. Do the data included in the product submission
provide substantial evidence of safety for the
requested indication?
2. Do the data included in the product submission
provide substantial evidence of effectiveness for the
requested indication?
3. Do the available data indicate that the benefits outweigh the risks of the device when used for the
requested indication?
This change permits the panel members to focus on
the scientific issues, which are more likely related to their
expertise, instead of the regulatory issues with which they
might not be familiar.

Classification of Devices
Different parts of the world use different classification
approaches as illustrated in Table 34-2.
Europe
Europes classification system of medical devices is
defined in EU directives on medical devices.8 These topdown classification rules are based on criteria such as the
duration of contact with the patient (less than 60 minutes,
not more than 30 days, and more than 30 days), the
degree of invasiveness, and the part of the body affected
by the use of the device.
United States
In the United States, the FDA was required to classify all
medical devices into one of three categories per the 1976
amendments, based on the intended use of the device.
Intended use refers to objective intent of the persons legally
responsible for the labeling of a medical device. The FDA
expects the intended use to address:
The intended medical indication
The intended patient population
The intended part of the body or type of tissue
applied to or interacted with
The intended user
The conditions of use
The operating principle

34 Standards and Regulatory Considerations

699

TABLE 34-2 S
 ummary of Classification Systems and Approval and Clearance Processes of Medical
Devices in Selected Countries and Regions
Country

Primary Agency

Classification (Legal Basis/Classes)

Canada

Health Canada
(www.hc-sc.gc.ca)

China

State Food and Drug


Administration (former.
sfda.gov.cn). The
General Administration
of Quality Supervision,
Inspection, and
Quarantine is responsible for electrical safety
European Union (ec.
europa.eu/)

Food and Drugs Act (RSC, 1985, c. F-27)


Invasive vs. noninvasive vs. active devices
Classes I to IV
Regulations for the Supervision and Administration of
Medical Devices (Decree 276 of State Council, 2000)
Class I: routine administration
Class II: further control
Class III: strict control
Includes devices implanted into the human body, those
used for life support or sustenance, and those that
pose potential risk to the human body
Active Implantable Medical Device Directive 90/383/EEC
Medical Device Directive 93/42/EEC
In Vitro Diagnostic Medical Device Directive 98/79/EC
Risk-based classification
Pharmaceutical Affairs Law
Class I: general
Class II: certification
Class II: approval
Class III: approval
Class IV: approval
Title 21 United States Code
Class I: general controls

European
Union
Japan

Ministry of Health Labor


and Welfare (MHLW)
(www.mhlw.go.jp/engl
ish/)

United States

Food and Drug Administration (www.fda.gov)

Class II: performance standards/special controls


Class III

Premarket
Placing on Market*
Establishment
license
Device license
Product registration
certificate
Licensing of
manufacturers
and distributors

Compliance label
(CE marking)
Responsible person
registration
PMDA Notification
Third-party
certification
MHLW approval

Establishment
registration
Classification and
finding of substantial equivalence
(510[k]) or PMA

*Premarket (product control/tools for acknowledging product cleared for the market); placing on market (medical device/establishment
control).
EC, European Commission; EEC, European Economic Community; PMA, premarket approval; PMDA, premarket drug approval.

The class I to class III designations are used by the


FDA to denote increasing scrutiny and controls. The
classification of devices was originally determined by panels of experts, who advised the FDA following the adoption of the 1976 amendments. Of the initial 1750 generic
types of devices classified, 40% were class I, 50% were
class II, and 10% were class III. Device types were grouped
into 16 medical specialties referred to as panels. The panels assigned each device type to one of the three regulatory classes based on their assessment of the level of
control necessary to assure the safety and effectiveness of
the device. The classification is risk based, that is, the risk
the device poses to the patient and/or the user is a major
factor in the class to which it was assigned. Class I includes
devices with the lowest risk, and class III includes those
with the greatest risk. The class to which a device is
assigned determines, among other things, the type of premarketing submission/application required for FDA
clearance to market. If a device is classified as class I or II,
and if it is not exempt, a 510(k) notification is required for
marketing. All medical devices classified as exempt are not
subject to premarket review, but the manufacturer is
required to register the device with the FDA. For class III
devices, a PMA is required unless the device is a preamendment device (on the market prior to the passage of
the Medical Device Amendments in 1976, or substantially
equivalent to such a device), in which case a 510(k) is

required. The FDA has nearly completed the task of


either downgrading all preamendment class III devices
into class II or calling for a PMA. Once this task has been
completed, there will no longer be any class III preamendment devices on the market via the 510(k) process. In
essence, the FDA classification system is bottom-up and
based on the state of knowledge and medical devices in
the late 1970s with some subsequent modification.
All classes of medical devices are subject to General
Controls, which are the baseline requirements of the
FD&C Act that apply to all medical devices, class I, II,
and III.
Despite the congressional mandate to write performance standards for all class II medical devices, this task
overwhelmed the CDRH, which had inadequate
resources. In response the FDA gave tacit approval to
existing national or international standards for this purpose. In doing so, the FDA was not relieved of the
responsibility to formulate mandatory performance
standards; however, they had indicated informally that
their limited resources would not be used where voluntary standards were in effect. The process by which the
FDA was to develop a mandatory performance standard
was quite complex and involved an FDA-appointed
Standards Advisory Committee. To date, only the apnea
monitor standard has been developed by this process.9
As such, voluntary standards were sought and have

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PART VII Safety, Standards, and Quality

become widely used, because they represent an excellent


starting point. The use of externally developed voluntary
consensus standards was helped by the Pentagon and its
allies, who persuaded the Office of Management and
Budget to issue Circular A-119 in 1982, urging federal
participation in the development and use of voluntary
consensus standards.10 Circular A-119 was revised and
strengthened in 1993.
At present, it is noted that the CDRH believes that
conformance with recognized consensus standards can
support a reasonable assurance of safety and/or effectiveness for many applicable aspects of medical devices.11
The current list of recognized standards maintained
on the FDAs Web site (www.accessdata.fda.gov/scripts/
cdrh/cfdocs/cfStandards/search.cfm) and the standards
program are managed by the CDRH Standards Management Staff (SMS). The SMS had been part of the Office
of Science and Engineering Laboratories (OSEL) but
was elevated to the Office of the Center Director in 2011.
SMS is responsible for facilitating the recognition of
national and international medical device consensus standards within the CDRH and FDA. The CDRH standards
program was created to address the Congressional mandate contained in the FDA Modernization Act (FDAMA)
of 1997. SMS ensures appropriate medical device standards are published in the Federal Register at least twice
annually. Manufacturers are permitted to use recognized
standards to simplify their premarket applications to the
FDA. Although CDRH had been involved in the development of medical device standards for decades, FDAMA
formalized the process.
Class I: General Controls. Class I medical devices were
subject only to general controls to ensure safety and
effectiveness. These controlling regulations 1) required
that devices be registered; 2) prohibited adulteration or
mislabeling of items; 3) provided for notification of risks,
repair, replacement, or refund; 4) restricted the sale and
distribution of certain devices; and 5) required GMPs as
defined by the FDA.
Class II: Performance Standards and Special Controls. Medical devices in class II had to meet performance
standards, because general controls were not considered
sufficient to guarantee their safety and effectiveness.
These devices had to fulfill all requirements of class I in
addition to FDA performance standards.
Class III: Substantial Equivalence. A new class III
medical device that was available commercially after the
enactment date could attempt to claim substantial
equivalence to an existing preamendment class III
device and thus ride on the coattails of similar, older
devices. This was provided for under section 510(k) of
the FD&C Act. If a manufacturer chose the 510(k)
route, the FDA needed PMN. Should the FDA have
decided that substantial equivalence did not apply to the
particular device, it had to be classified as a class III
device. As such, it required PMA and review by the
Anesthesiology and Respiratory Devices Review Panel
before it could be marketed. The manufacturers only
other option was to re-petition for reclassification of

their device to class I or class II. The FDA generally


ruled that a device was not substantially equivalent if 1)
its intended use was different, 2) it raised new questions
about safety or effectiveness, or 3) it did not perform as
well as devices already on the market.

Classifying a Device in the United States


To find the classification of a device, the classification
regulation for the device of interest needs to be found
either using the FDAs on-line classification database
(Web site) or using the device panel. Part 868, entitled
Anesthesiology Devices, includes subparts for diagnostic,
monitoring, therapeutic, and miscellaneous devices.
Each classified device within each part has a sevendigit number associated with it, referring to the specific code in Title 21 of the Federal Regulations, where
it is defined. An anesthesia machine is listed under 21
CFR 868.5160 as a gas machine for anesthesia or
analgesia and is defined as:
(a) Gas machine for anesthesia
(1) Identification. A gas machine for anesthesia is a device
used to administer to a patient, continuously or intermittently, a general inhalation anesthetic and to maintain a
patients ventilation. The device may include a gas flowmeter, vaporizer, ventilator, breathing circuit with bag, and
emergency air supply.
(2) Classification. Class II (performance standards).
(b) Gas machine for analgesia
(1) Identification. A gas machine for analgesia is a device
used to administer to a patient an analgesic agent, such as
a nitrous oxideoxygen mixture (maximum concentration
of 70 percent nitrous oxide).
(2) Classification. Class II (performance standards).

Premarket and Placing-on-Market


Processes
The processes and tools used to evaluate a product
before permitting its introduction to market vary considerably among countries (see Table 34-2). In the
United States, the approval process (PMA) and marketing clearance (510[k]) of the FDA (see Table 34-1)
are most often used to place products on the market in
the United States. The EU requires compliance with
its directives prior to applying CE-marking and the
placement of a product in commerce. For medical
devices, a manufacturer must demonstrate that the
medical device meets the essential requirements of the
Medical Device Directive8 by creating a technical file
with the appropriate evidence and creating a Declaration of Conformity signed by a representative of the
company prior to introduction. For manufacturers
outside the EU, this material must be accessible to a
designated Authorized Representative within the EU.
The CE-marking approach is intended to ensure free
movement of goods and services within the European
common market.
Canada requires obtaining a license with the process
similar to that of the 510(k) in the United States, from a
paperwork perspective. In Asia a wide variety of listings,

34 Standards and Regulatory Considerations

registrations, and approvals for medical devices exist that


range from a simple addition of the medical device to a
list to very involved approval processes that require incountry clinical evaluations.

Pending Regulatory Changes in the United


States
What is happening in the United States with respect to
changes in to the 510(k) and other processes? Following
a 1-year internal assessment in August 2010, CDRHs
510(k) Working Group published a preliminary report12
consisting of more than 60 recommendations grouped
under six findings aimed at improving the Centers
effectiveness in implementing its various missions. The
preliminary report focused on three major areas: the
need for 1) a rational, well-defined, and consistently
interpreted review standard; 2) well-informed decision
making; and 3) continuous quality assurance. The report
found:
1. There is insufficient clarity with respect to the definition of substantial equivalence.
2. CDRHs current practice allows for the use of some
types of predicates that may not be appropriate.
3. The de novo pathway is important and has not been
optimally used across the Center.
4. It is challenging for reviewers to obtain the information they need to make well-supported clearance
decisions.
5. The CDRHs knowledge management infrastructure is limited.
6. Variations in the expertise, experience, and training
of reviewers and managers, including third-party
reviewers, may contribute to inconsistency or
uncertainty in 510(k) decision making.
The report committed the FDA to create a large number of new or revised guidance documents aimed at
improving the 510(k) program.
The FDA also commissioned the IOM to evaluate the
current 510(k) process to see whether it protects patients
and promotes innovation, and if not, to evaluate what
legislative, regulatory, or administrative changes are recommended to best achieve the goals of the 510(k) process. The IOM report includes an excellent summary of
the history of the reform of the 510(k) process. It was
issued in July of 2011 and found that the current 510(k)
process:
Does not determine safety or efficacy of a medical
device
Lacks the legal basis to screen a medical device for
safety and efficacy
Was never intended to do either of the above
The IOM report indicated that rather than continuing to modify the 35-year-old 510(k) process, the IOM
concludes that the FDAs finite resources would be better
invested in developing an integrated premarket and postmarket regulatory framework.7 The day the IOM report
was published, the FDA immediately rejected its conclusion and announced the 510(k) process should not be
eliminated, but the FDA is open to additional proposals
and approaches for continued improvement of our device
review program.13

701

The FDA has continued to follow through on its


commitments from the 510(k) preliminary report with
the following objectives:
Create new or update existing guidances for clarity
Integrate systems and databases to make information more accessible
Issue regulations to cover previously neglected
items and transfer of ownership of a 510(k).13

MEDICAL DEVICE VOLUNTARY


STANDARDS
Overview
Work on standardizing medical equipment began because
of incompatibilities that became obvious during World
War II.10 Voluntary consensus standards for medical
devices have been in use for the past few decades, and
commercial standards have existed for well over 100
years. These standards often codify commonly used and
long-standing practices. Commercial standards may be
developed solely within a company, by a trade group, or
by a technical society. Generally, in the United States the
writing of standards is essentially a bottom-up process
that formalizes existing and accepted commercial or
industrial processes and experience.
On the international level, standards are dichotomized
much as they are nationally. Older multinational standards organizations, such as the International Organization for Standardization (ISO) and the International
Electrotechnical Commission (IEC), work on the basis of
voluntary consensus. ISO members are the National
Standardization Institutes of 163 countries and its staff at
the Central Secretariat in Geneva, Switzerland, coordinating and supporting the creation and marketing of ISO
standards. ISO member bodies (www.iso.org/iso/about/
iso_members.htm) may directly develop standards (e.g.,
Germanys DIN and the United Kingdoms BSI) or may
delegate another body to do so (e.g., ANSI in the United
States; Table 34-3). Other newer, multinational organizations with official regulatory authority are now
emerging.
The arena of voluntary consensus standards for medical equipment may not appear as orderly and regimented
as that of government regulation. In fact, it can be a
source of considerable confusion to the practicing anesthesiologist. This is especially true when an anesthesiologist wants to determine the current voluntary consensus
standard for a particular piece of equipment. Several different sets of voluntary standards from a number of different organizations often apply to a single medical device
(Table 34-4). Even the alphabet soup used to describe
the different organizationsAAMI, ANSI, NFPA, IEEE,
IEC, ISO, and ASTMcan be confusing.
Development of standards by the voluntary consensus
method is faster and more responsive to the marketplace
than methods used by either state or federal agencies.
Organizations that propose voluntary standards are not
subject to the cumbersome bureaucratic and legal intricacies that govern both federal and state governments. This is
not to say, however, that voluntary consensus organizations

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PART VII Safety, Standards, and Quality

TABLE 34-3 Selected Standard Development Organizations of Interest to Anesthesia


Scope

Organizations

Committee of Interest

Committee Focus/Comment

United States (domestic)

ASTM
AAMI
ANSI
IEEE
NEMA
NCCLS
CGA
BSI, DIN, JISC, SAC, ABNT
CEN (EU)
CENELEC (EU)
ISO

F29
U.S. TAG for IEC/SC 62D

Anesthesia
Safety

EMB/11073
MITA

Communications

IEC

SC 62A, 62D

United States (foreign)


Regional
International

Radiology, in vitro diagnostics


TC 121
TC 215
TC 62
TC 121; TC 210

Anesthesia
ISO TC 121 mirror
IEC TC 62 mirror
Anesthesia; quality systems
and risk management
Electrical aspects

AAMI, Association for the Advancement of Medical Instrumentation; ABNT, Associao Brasileira de Normas Tcnicas (Brazilian Association of
Technical Standards); ANSI, American National Standards Institute; ASTM, American Society for Testing and Materials; BSI, British Standards
Institute; CEN, Comit Europen de Normalisation (European Committee for Standardization); CENELEC, Comit Europen de Normalisation
lectrotechnique (European Committee for Electrotechnical Standardization); CGA, Compressed Gas Association; DIN, Deutsches Institut fr
Normung (German Standards Institute); IEC, International Electrotechnical Commission; IEEE; Institute of Electrical and Electronic Engineers;
ISO, International Organization for Standardization; JISC, Japanese Industrial Standards Committee; MITA, Medical Imaging and Technology
Alliance; NCCLS, National Clinical and Laboratory Standards Institute; NEMA, National Electrical Manufacturers Association; SAC, Standardization Administration of China; SC, Scientific Committee; TAG, Technical Advisory Group; TC, Technical Committee.

TABLE 34-4 Selected Recognized, Harmonized, and Particular Standards in Relation to Technology
FDA

MDD

Latest International
Particular Standard
(ISO, IEC, ASTM)

Product
Code(s)*

Recognized Consensus Standard

Harmonized
Standard

Related Clinical
Guidelines

Anesthesia
workstation

IEC 60601-2-13: 2011

BSZ

IEC 60601-2-13
Ed 3.1: 2009

EN 60601-2-13: 2006

Anesthetic
agents
monitor
Carbon dioxide
monitor

IEC 80601-2-55: 2011

CBQ, CBS, CBR

ISO 21647: 2004

EN ISO 21647: 2009

IEC 80601-2-55: 2011

CCK

ISO 21647: 2004

EN ISO 21647: 2009

Pulse oximetry

IEC 80601-2-61: 2011

DQA

EN ISO 9919: 2009

Oxygen
monitor

IEC 80601-2-55: 2011

CCL

ISO 9919: 2005


IEC 80601-2-61
Ed 1.0: 2011
ISO 21647: 2004

Machine checklist,
obsolescence, gas
disposal (ASA,
FDA, institutional,
government)
Regulatory bodies
with respect to
gases
AARC (CPG, 2011)
Numerous
anesthesia
guidelines for
different settings
(e.g., ASA)
CLSI (POCT11-A2)
AARC (CPG-1992)
ASA
AARC (various CPGs)

Equipment

EN ISO 21647: 2009

*Per http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm.
As of March 1, 2012, per http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.
As of March 1, 2012, per http://ec.europa.eu/enterprise/policies/european-standards/harmonised-standards/medical-devices.
AARC, American Association for Respiratory Care; ASA, American Society of Anesthesiologists; CLSI, Clinical Laboratory and Standards Institute;
CPG, clinical practice guideline; EN, European Committee standard designator; FDA, Food and Drug Administration; IEC, International Electrotechnical Commission; ISO, International Organization for Standardization; MDD, Medical Device Directive; POCT, point-of-care testing.

can be cavalier or ignorant with regard to legal requirements. In the interest of fairness and to prevent legal ramifications, all interested parties are allowed to participate in
the process of creating standards in accordance with the
individual organizations bylaws.

Compliance with voluntary standards is not mandatory, because the parent organization has no legal jurisdiction. Voluntary consensus standards, however, often
have an influence even before they are finalized. Responsible manufacturers find both legal protection and sales

34 Standards and Regulatory Considerations

advantages in claiming that their equipment meets various voluntary standards, such as those of AAMI, ANSI,
IEC, ISO or ASTM. New voluntary standards cannot
require that a manufacturer remove from the marketplace
earlier equipment that does not conform to the new standard. Only a municipal, state, or federal authority having
jurisdiction can demand compliance or remove an item
from the market. Often, voluntary consensus standards,
such as those of the National Fire Protection Association
(NFPA), are adopted by local agencies that have the
authority to turn the standards into law. Voluntary equipment standards can also be adopted by a government
agency as part of their procurement or purchasing policies. On occasion, however, a governmental regulation
may be adopted before the voluntary standard has been
finalized.

Stages in the Development of International


Standards
An international standard is the result of an agreement
among the member bodies of an organization. It may be
used as such, or it may be implemented through incorporation in national standards of different countries. International standards are developed by technical committees
and subcommittees. Many such committees follow a sixstep process. The six-step process followed by ISO affiliated committees is shown in Figure 34-2 with the activity,
documents, and elapsed time for each stage noted.14 ISO
standards are reviewed at the least 3 years after publication and every 5 years thereafter by all the ISO member
bodies. A majority of the participating members of the
technical committee (TC) or scientific committee (SC)
decides whether an international standard should be confirmed, revised, or withdrawn.
Within organizations such as ISO, standardization is an
open, voluntary process built around consensus, and it is
stakeholder driven. Within the ISO, the committee of relevance to anesthesia is TC 121, Anaesthetic and Respiratory

Proposal stage

Activity in stage

Elapsed time
(months) (default)

Equipment. The stakeholders in TC 121 include equipment manufacturers, clinicians, regulatory agencies, test
houses, and others. Created in 1966, TC 121 has a scope
defined as standardization of anaesthetic and respiratory
equipment and supplies, related devices, and supply systems. It is responsible for 85 standards among its subcommittees (see Table 34-3) and includes 25 participating and
24 observing countries. Also of importance is the IEC,
which has a committee responsible for developing international standards for electrical equipment used in medical
practice (IEC TC 62), whose subcommittee D is responsible for electromedical equipment (e.g., the nonradiology
particular medical electrical device standards of the 60601-2
series).
Given the wide variety of equipment on the market, it
is often not clear which organization should be responsible. So that the expertise of both organizations may be
made available in the development of standards, joint
working groups (JWGs) between ISO and IEC are often
formed. In these cases, either ISO or IEC may take the
lead. For each JWG, one of national standards bodies,
which for ISO is a member body and for IEC is a national
committee, accepts responsibility for administering the
JWG, and that organization holds the secretariat and
appoints one or two individuals to handle the technical
and administrative work. A convenor (chairman) runs the
meetings and works to reach consensus. Frequently a
JWG has a secretary who manages the documents and
works closely with the convenor.
Within each committee, and as part of the standards
development processes, are important roles to play,
both nationally and internationally. Clinician involvement is crucial to the development and revision of medical device standards. Participation can be as an expert
in a working group, a member of a national delegation,
and even as a head of a national delegation. Experts
attend meetings in their own capacity as experts, but
they must be aware of the position of the national body
of the country they represent. Influence may be wielded

Preparatory stage Committee stage

1 - New work Item


Proposal (NWIP)

2 - Working Draft(s)
(WD)

Formal voting by ISO


member bodies
whether to work on
document

Building expert
consensus

3 - Committee Draft(s)
(CD)

Consensus building
within Committee

Month

1 2 3 4 5 6 7 8 9 10 11 12

Stage

WD

ISO Technical Committee time Document being developed in


relevant committee.

703

Enquiry stage

4 - Draft International
Standard (DIS)

Commenting and
formal voting on
document within ISO

Approval stage

Publication stage

5 - Final Draft
International Standard
(FDIS)

6
International Standard

Formal vote by ISO


member bodies

13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

CD

DIS

ISO Central Secretariet timeDocument being processed (e.g.,


evaluation, editing, and proofreading).

Comments
resolution

FDIS

ISO Member body timeDocument circulated to ISO


member bodies for DIS/FDIS vote.

FIGURE 34-2 n The consensus-building stages of standards. Note: Committee draft, draft International Standard, and final draft International Standard documents are approved only if a two-thirds majority of the participating member bodies of the technical and
scientific committees are in favor, and not more than one quarter of the total number of votes cast are negative.

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PART VII Safety, Standards, and Quality

through formal approacheswritten comments, discussions, drafting of resolutions, and votingand by informal means, such as lobbying members of other
delegations and through personal relationships.

Organization of Standards Development


Organizations
The scope of standards that the standards development
organization (SDO) develops varies considerably. It may
represent a technical area (e.g., electrical, pneumatic), or
it may be application oriented (e.g., clinical). Sometimes
the scope may not be clear. In the case of ISO and IEC,
the technical divisions are often not clear, and JWGs exist
to allow members of both bodies to participate. Agreements have been signed between different regional and
international SDOs to help clarify the roles and responsibilities to reduce duplicative activities and promote cooperation. The Committee for European Standardization
(CEN) and Committee for European Electrotechnical
Standardization (CENELEC) have agreements with
their international counterparts, ISO and IEC, defining
the rules governing cooperation. The Vienna (1991) and
Dresden (1996) Agreements signed between CEN and
ISO and CENELEC and IEC, respectively, helped to
create the framework for cooperation between European
and international standards activity with the explicit recognition of the primacy of international standards and
goal of simultaneous recognition at the international and
European level.
For in vitro diagnostics, the Clinical and Laboratory
Standards Institute (CLSI), formerly the National Committee for Clinical Laboratory Standards (NCCLS),
develops the preponderance of relevant standards. The
CLSI also is the international secretariat of ISO TC 212,
Clinical Laboratory Testing and In Vitro Diagnostic
Test Systems, which gives CLSI a pathway to have its
standards become European standards via the Vienna
Agreement with CEN.
Other standards or guidelines may be developed primarily by medical societies, which include societies such
as the American Thoracic Society, American Society of
Anesthesiologists (ASA), and American Association for
Respiratory Care.
Standards come into existence in three ways: 1) by
national or international recognition (ISO, IEC, ASTM,
etc.); 2) by common use (de facto standards, such as MS
Windows), and 3) by industry consortia.
SDOs have certain defining characteristics. First, they
follow a very formal standards development process. Second, they have broadly inclusive participation structures
composed of representatives from all members of a given
class, because an international SDO must include a representative from each nation. Third, open discussion and
debate occurs on all issues, and due process gives members the opportunity to lodge formal complaints and
appeals to the establishment of given standards. Finally,
democratic voting procedures are available that emphasize consensus as opposed to majority or plurality rule.
Because of these characteristics, standards issued by
SDOs have a high degree of legitimacy, derived from the
process that created them.

SDO standards do offer stability and support. On the


other hand, these same characteristics generate criticism
of SDOs, which are often too slow with respect to market
time frames. Redundant and parallel structures exist,
especially within the country representatives to international SDOs. Therefore SDOs are inefficient; they are
too focused on consensus and hence are often reduced to
choosing the least common denominator, which often is
not an ideal solution to many users. Voting structures are
out of sync with the economic investment of participating
members, and participation of nonstakeholder members
drags out the process. SDOs cost too much (e.g., AAMI),
and their processes are out of date. While technically apt,
committee members lack experience and writing skills to
produce draft standards quickly, and SDOs do not effectively prioritize drafts that need to be considered first.
Unlike European and Pacific Rim countries, the United
States is not represented at international standards organizations by any official governmental representative, and
the United States does not have a single body that speaks
for all standards activities within the country.
At present ANSI serves as the coordinator and formal
representative for the United States before the ISO and
the IEC. However, ANSI delegates the responsibility for
actually doing the work to other SDOs within the United
States (e.g., AAMI, ASTM, CLSI). The General Agreement on Tariffs and Trade (GATT), to which the United
States has been a signatory since the late 1940s, was
replaced by the World Trade Organization (WTO) in
1994. Under these international trade agreements, there
exists a Standards Code that provides ground rules for
preparing, ratifying, and implementing international
technical standards to be used to prevent technical barriers to trade. ANSI has assumed the role of representative
for the United States, but in contrast to many of its counterparts in Europe, it has no official governmental
sanction.
Several non-U.S. SDOs of interest include both
regional (e.g., CEN and CENELEC) and national SDOs
(e.g., DIN, BSI), which also may serve as the ISO or IEC
member body.

U.S. Standards Development Organizations


of Interest
American National Standards Institute (ANSI)
The anesthesia community has a long history of involvement with ANSI, a private, nonprofit organization
founded more than 70 years ago to coordinate and facilitate the development of standards. In 1956 the ASA
assumed the secretariat of ANSI Committee Z-79 for
Anesthesia and Respiratory Therapy Equipment, and
they maintained this position until 1983. During this
time, many standards were produced by the Z-79 Committee, including those for humidifiers, reservoir bags,
ventilators, tracheal tubes, and anesthesia machines. Probably the most important and best-known standard created
by the Z-79 Committee was the Z-79.9 1979 standard for
anesthesia machines.15 This was the first attempt by the
manufacturers and users of anesthesia equipment to
ensure compatibility and performance among the various

34 Standards and Regulatory Considerations

types of anesthesia machines. Although this standard contained flaws, it was the best standard that could be developed at the time through voluntary consensus efforts.
However, the standard was deficient in some major areas.
For example, it permitted the use of in-circuit vaporizers
and required neither oxygen analyzers nor a method to
prevent the administration of a hypoxic mixture. It did,
however, serve the anesthesia community well, both manufacturer and user, during the 10 years it functioned as the
ruling anesthesia machine standard. National standards
activity in this area was transferred by committee vote in
1983 from ANSI to ASTM.
ASTM International
Formerly the American Society for Testing and Materials, ASTM International currently handles most of the
activities concerning voluntary standards that affect anesthesia durable equipment. Committee F-29 on Anesthetic and Respiratory Therapy Equipment has 10
subcommittees that focus on safety and performance
standards rather than on design or specific engineering
standards. Design and engineering decisions are best left
to the individual manufacturer. ASTM views standardswriting activities as a method to achieve an orderly
approach to a specific activity or problem. All committee
members are volunteers; the formal ASTM staff provides
only administrative support. ASTM does not fund any
participants, nor does it have its own laboratory facilities;
individual members must have their own funding. At
present, the ASA funds the travel of its liaison to Committee F-29.
Under ASTM bylaws, the members of any committee
should reflect a balance of users, producers, ultimate consumers, technical representatives, insurers, educators,
and those with an interest in the area. The last category
can include members of the FDA or of nonprofit health
care organizations that deal with medical devices directly
or indirectly.
Almost anyone can initiate the creation of a standard
within ASTM. The proponent must first submit a written
request detailing the various companies, individuals, and
organizations participating. The executive staff of ASTM
then decides whether the proposal has merit. If accepted,
the proposal is then referred to a particular committee.
Association for the Advancement of Medical
Instrumentation (AAMI)
AAMI is a nonprofit organization founded in 1967. It is a
unique alliance of more than 6000 members from around
the world united by one mission: to provide global multidisciplinary leadership and programs that enhance the
goals and capabilities of the professions, health care institutions, government, industry, and other organizations
that relate to the delivery, development, management,
use, and other aspects of safe and effective medical instrumentation and related technologies. The AAMI standards
program consists of over 100 technical committees and
working groups that produce Standards, Recommended
Practices, and Technical Information Reports for medical
devices. Standards and Recommended Practices represent

705

a national consensus, and many have been approved by


ANSI as American national standards. AAMI also administers a number of international health care technical
committees of ISO and IEC in addition to U.S. Technical
Advisory Groups (TAGs).
National Fire Protection Association (NFPA)
The anesthesia community has been involved with voluntary standards for almost 40 years. Initially, the ASA participated in the development of standards by the NFPA,
which writes standards for many aspects of fire prevention, detection, and suppression. The NFPA also
addresses standards for different types of facilities, such as
multiple dwellings, factories, and hospitals. Initially,
when cyclopropane and ether were used in operating
rooms (ORs), the input of anesthesiologists was important in developing standards for anesthetizing locations.
Their input was again needed with the advent of centralized medical-gas distribution systems, such as for oxygen
and nitrous oxide. What initially developed as fire safety
regulations for all occupants of a facility eventually
evolved into patient safety standards. An example of this
is the present NFPA standard for nonflammable medicalgas piping systems.
Anesthesiology input has remained vital to the NFPA
throughout the years, both to provide user input and to
ensure that proposals by fire professionals for changes or
modifications do not adversely affect the hospitals clinical practice. For instance, a firefighter cannot elect to
turn off the hospitals entire oxygen supply because of a
fire in one wing of the facility. Obviously, the drafting of
such a standard requires compromise on the part of both
clinicians and fire professionals.
All standards published by the NFPA that affect hospitals are now published in one document: the NFPA 99
Health Care Facilities Code.16 This document is generally updated every 3 years and was most recently updated
in 2012. It contains standards governing anesthetizing
locations, emergency power supplies, high-frequency
electricity, medical-gas pipeline systems, and hyperbaric
oxygen facilities.
In the newest edition, NFPA-99 has changed from a
standard to a code. It has been rewritten to be a riskbased, rather than an occupancy-based, document. That
means the requirements are based on whether a system
failure would cause a high, moderate, or low risk to a
patient. Therefore wherever general anesthesia is being
administered to patients, appropriate back-up systems
must be in place for things such as oxygen and electrical
power: it no longer matters if the facility is a 50 OR medical center or a two-room freestanding outpatient facility.
Other changes to NFPA-99 include a provision that
all new or remodeled ORs will default to being a wet
location. That means that special electrical protection in
the form of isolated power or ground fault circuit interrupters (GFCIs) will have to be installed, unless the facility does a risk assessment to prove that certain ORs are
not wet locations. Other relevant changes include a
requirement for all electrical/gas booms to be inspected
on a regular basis and for a minimum of 18 electrical outlets to be installed in a critical care area and 36 in an OR.

706

PART VII Safety, Standards, and Quality

Although ether and cyclopropane are no longer used


in modern ORs, the threat of fire has in no way been
eliminated. Each year the amount of electrical equipment
in the OR increases. Many of these devices, such as electrosurgical units (ESUs) and lasers, can ignite drapes,
sponges, and other disposable items in an OR. In the
presence of oxygen or nitrous oxide, a spark can become
a conflagration (see also Chapter 31). A number of organizations have become interested in the prevention of OR
fires. In 2008 the ASA issued a Practice Advisory on OR
fire prevention.17 Also, in 2010 the Anesthesia Patient
Safety Foundation (APSF; www.apsf.org) produced a
video with new recommendations on the prevention of
OR fires, Prevention and Management of Operating Room
Fires. Other organizations that have made efforts to prevent OR fires include the ECRI Institute18 and the Association of Operating Room Nurses (AORN).
Institute of Electrical and Electronics
Engineers (IEEE)
The IEEE has traditionally written standards that
directly concern only engineers. One project within
IEEE of particular interest to the anesthesia community concerns the work of IEEE Committee P-1073,
which has been developing medical communications
standards since 1987; the idea originated during the
early 1980s, after the AAMI sponsored a roundtable
discussion in 1982 on developing standards for data
management in monitoring. Many of those attending
the session thought that a standardized method for data
communication among monitoring equipment was
needed in the OR. A proposal was subsequently made
by the AAMI Standards Board that a technical committee be formed to develop standards for monitoring system data management. However, no further action was
taken by AAMI.
In 1987, this subject was taken up by Committee
P-1073 of the IEEE Engineering in Medicine and Biology Society (EMBS), which consisted of device manufacturers, computer experts, clinicians, and biomedical
engineers. The Committee undertook to produce standards for local area networks (LANs) to enable communication among freestanding monitors, infusion and
life-support devices, and a host computer system. This
was not to serve laboratory or pharmacy functions but
rather was intended solely to support the clinician in an
acute patient-care setting, such as the intensive care unit
(ICU) or OR.
These standards specifically make provisions for anesthesia machines and ventilators with the purpose of
developing an automated anesthesia record using local
intelligence, which can be uploaded to a large host computer system. The goal is to eliminate the need for individual institutions to write software or design connectors
for devices. The standards therefore are vendor
independent.
It has taken more than two decades, but Committee
P-1073 has written a series of standards for point-of-care
medical device communication, the IEEE 11073 series,
many of which have also been adopted by ISO TC 215,
Health Informatics.

Medical Device Standards


ISO and IEC standards follow the same basic structure:
Scope defines without ambiguity the subject of the
standard and the aspects covered, thereby indicating the limits of applicability of the standard.
Normative references give a list of the referenced
documents cited in the standard in such a way as to
make them indispensable for the application of the
standard.
Terms and definitions give the definitions necessary
for the understanding of certain terms used in the
standard.
Requirements contain clauses that have all of the dictates, statements, and recommendations or references to them necessary to claim compliance to the
standard.
Annexes, both normative and informative, give provisions additional to those in the body of the document. Annex AA, which is found in many ISO and
IEC health care standards, contains particular guidance and rationale that includes useful explanations
to the reader and user of the standard. This allows
an interpretation more aligned to what was intended
by the developer of the standard. Another annex
commonly found is an Annex reference to the
essential principles (of ISO 16142).
The General Standard (60601-1)
The IEC 60601-1, developed by IEC TC 62, is a family of
technical standards for the basic safety and essential performance of medical electrical equipment, comprising the
general standard, a series of 11 collateral standards, and
over 70 particular standards. At present, three editions
have been published: the first in 1977, the second in 1988,
and the third in 2005. The general standard is formally
known as IEC 60601-1, Medical Electrical Equipment,
Part 1: General requirements for basic safety and essential
performance.19 IEC 60601-1 contains the general requirements for medical electrical equipment. Compliance with
IEC 60601-1 has become a de facto requirement for the
commercialization of electrical medical equipment in
many countries. It is harmonized with the MDD, needed
for CE-marking, and is recognized by the FDA.
Although this is an international standard, each country does have the right to recognize the standard in whole
or with deviations, changes to specific clauses, for countryspecific requirements. The deviations may be minor or
significant. The U.S. deviations are published as a cover
to the international standard and are known as AAMI ES
60601-1.
The latest edition of this standard, the third edition,
was published in 2005. It resulted from an understanding
of the recognized deficiencies of the second edition and in
particular the need to address the safety performance of
medical electrical equipment. It is the work of 11 working
groups involving over 200 people over a period of 10 years.
Key changes in the third edition include the overall
structure and the numbering scheme of the clauses. The
application and visibility of risk management was
increased by adding requirements for the establishment

34 Standards and Regulatory Considerations

of a risk management process per ISO 14971, the establishment of acceptable levels of risk, and demonstration
that the residual risks are acceptable (according to the
manufacturers policy for determining acceptable risk).20
The concept of essential performance (EP) or safetyrelated performance was introduced and defined as the
performance of a clinical function, other than that
related to basic safety, where loss or degradation beyond
the limits specified by the manufacturer results in an
unacceptable risk.19 EP is most easily understood by
considering whether its absence or degradation would
result in an unacceptable risk. The process of creating
third editioncompliant versions of all of the related published standards is ongoing, and manufacturers and users
of the standards will have to deal with both the second
and third edition versions of the particular standards until
the transition periods in all countries are completed.
For many specific product types, a standard has been
developed using the general standard as a template with
additions, deletions, and changes made to specific clauses,
thereby creating what is known as a particular standard,
numbered as IEC 60601-2-xx, where xx references the
particular device. Where the particular standard is the
product of an ISO/IEC joint working group, the standard
can be numbered 80601-2-xx, with either an ISO or IEC
prefix, determined by which organization had the lead for
the work. This is shown graphically for a couple of devices
in Figure 34-3.
Collateral standards (Table 34-5) have been created over
the years to add requirements for a subgroup of equipment,
such as for certain safety and performance aspects specific
to environments of use (e.g., home care), or related to a

60601-11
Closed loop
physiologic
controllers

707

specific characteristic of all equipment not fully addressed


in IEC 60601-1 (e.g., alarm systems or electromagnetic
capability [EMC]). For an FDA perspective on the role of
standards in medical devices EMC, see Silberberg.21
Standards of Particular Interest
Particular standards take precedence over the general
standard and collateral standards. Standards of particular
relevance to anesthesia are numerous. A number of these
standards that are the domain of TC 121 (Table 34-6) are
shown in Table 34-7. In addition, the breadth of coverage
of these standards is shown graphically in Figure 34-4.
This section highlights the key aspects and history of
three standards of particular interest to anesthesiologists:
1) anesthetic workstations, 2) respiratory gas monitors,
and 3) pulse oximeters. These medical device standards
and other standards can be given much of the credit for
the reduction in mortality and morbidity from anesthesia
over the past 30 years. These standards have included
important safety innovations, such as the introduction of
the diameter index safety system for connections for medicalgas hoses; the pin index safety system for medical-gas cylinders with post-type valves and cylinder mounting yokes;
color coding of gas cylinders and equipment; and the
incorporation of various fail-safes and protective features,
such as the keyed filling system for vaporizers, vaporizer
interlocks (which permit the use of only one vaporizer at
a time), and hypoxia prevention systems. Additionally,
many aspects of the anesthesia machine that have been
made standard often directly relate to solving known
problems or helping to reduce use errors. Over time

80601-2-13
Anesthetic
workstations

60601-8
Alarm systems

60601-2
EMC

60601-1
General
requirements

General standard and its


collaterals (part 1)

80601-2-55
Respiratory gas
monitors

Particular standards (part 2)

FIGURE 34-3 n Organization of International Electrotechnical Commission 60601, its collaterals, and
particular standards. Note that the
particular standard is dominant
and amends the general standard
and its collaterals.

708

PART VII Safety, Standards, and Quality

TABLE 34-5 Collateral Standards


Collateral Standard:
Year of Latest Edition

Title

Comments*

60601-1-1

Medical Electrical Systems

60601-1-2: 2007

Electromagnetic Compatibility (EMC)


Radiation Protection for
Diagnostic X-ray
Systems
Programmable Electrical
Medical Systems (PEMS)

Discontinued as a stand-alone document; incorporated into the third


edition.
Compliance means that the equipment will neither generate excessive
unwanted electromagnetic radiation nor be unduly affected by it.
Ensures that radiation is kept as low as reasonably achievable for the
safety of patient and operator.

60601-1-3: 2008
60601-1-4
60601-1-6: 2007

Usability

60601-1-8:2007+A1: 2012

Medical Alarm Systems

60601-1-9: 2008

Environmentally Conscious
Design

60601-1-10: 2008

Physiologic Closed Loop


Controllers

60601-1-11: 2010

Home Health Care


Equipment

60601-1-12 Ed 1 (under
development)

Equipment for Use in


Emergency Medical
Services Environment

This is a collateral standard for software. It has been discontinued as a


stand-alone document and is now incorporated into the third
edition.
Increases emphasis on ergonomics; manufacturers must take the
requirements into account during the design phase. Many adverse
incidents in the past have been traced to use error; intended to
control risks caused by usability problems.
Gives guidance and requirements in the prioritizing and management
of alarm functions in medical equipment. Alarm systems can be
chaotic if the user does not know what is going off and whether the
alarm condition is trivial or serious.
Design process requiring the manufacturer to consider contamination
of the air, water, and biosphere; the use of raw materials; and
transport and packaging in the design of new products.
Design process to be considered when designing medical devices
used to control the parameters they are measuring. Such systems
have to be stable, reliable, and fault tolerant. Software must be
designed methodically and validated comprehensively.
Puts considerable emphasis on the use of home health care equipment
by non-specialist users. Electrical safety is also a factor here and the
equipment must be tolerant of poor wiring in the building and wide
environmental limits.
Puts considerable emphasis on the use of emergency medical
equipment by users in crisis situations. Electrical safety is also a
factor, and the equipment must be tolerant of the extremely wide
environmental limits that can be found at the scene of an
emergency.

*Modified from http://www.mddionline.com/article/collateral-standards-iec-60601-1.

TABLE 34-6 Subcommittees of TC 121


Subcommittee/
Working Group
CAG
SC 1
SC 2
SC 3
SC 4
SC 6
SC 8

Title
Chairman Advisory Group
Breathing Attachments and
Anaesthetic Machines
Airways and Related Equipment
Lung Ventilators and Related
Equipment
Terminology and Semantics
Medical Gas Systems
Suction Devices for Hospital and
Emergency Care Use

the addition of monitors, anesthesia machine checkout


procedures, and the use of anesthesia simulators for
teaching have helped increase patient safety. These monitors include airway pressure monitors, tidal volume
monitors, oxygen analyzers positioned to sample inspiratory gases, carbon dioxide analyzers placed to monitor
exhaled gases from the patient, and pulse oximeters.

Anesthetic Workstations. Table 34-8 highlights the


changes in anesthesia machine/workstation standards,
both U.S. and international, and their sequence since the
advent of ANSI Z-79.8, the first anesthesia machine standard.15 Activity on the Z-79.8 standard began in about
1970, as members on the Z-79 Subcommittee on Performance of Anesthesia Gas Machines sought and collated
the problems which are being experienced with apparatus throughout the country, as a first step in the evolution
of pertinent performance specifications22 and concluded
with the publication of Z-79.8 in 1979, because the time
(was) long overdue for action on gas machine performance and safety standards.23 The committee work on
Z-79 for the anesthesia machine gave rise to a number of
standards,24 including those for humidifiers25 and 15- and
22-mm connectors. When the F1161-88 standard26 was
published about a decade later and followed by F18500027 in 2000, many in the anesthesia and regulatory community hoped that all gas machines predating the Z-79
standard would be retired. Recent studies have shown
this not to be the case. It is unfortunate that many anesthesia machines more than 30 years old are still being
used in obstetrical units, radiology suites, and emergency
rooms, even though they do not reflect the current state

34 Standards and Regulatory Considerations

709

TABLE 34-7 Selected Published Standards under the Responsibility of ISO TC 121 SC/1 and SC/6
Title

Standard

Anaesthetic and respiratory equipment, Conical connectors. Part 1: Cones and sockets
Anaesthetic and respiratory equipment, Conical connectors. Part 2: Screw-threaded weightbearing connectors
Anaesthetic machines for use with humans
Low-pressure hose assemblies for use with medical gases

ISO 5356-1:2004
ISO 5356-2:2006

Anaesthetic vaporizers: Agent-specific filling systems


Inhalational anaesthesia systems. Part 7: Anaesthetic systems for use in areas with limited
logistical supplies of electricity and anaesthetic gases
Gas mixers for medical use: Stand-alone gas mixers
Inhalational anaesthesia systems: Draw-over vaporizers and associated equipment
Medical electrical equipment. Part 2-13: Particular requirements for basic safety and essential
performance of an anaesthetic workstation
Medical electrical equipment. Part 2-55: Particular requirements for the basic safety and essential
performance of respiratory gas monitors
Medical supply units
Medical gas pipeline systems
Part 1: Pipeline systems for compressed medical gases and vacuum
Part 2: Anaesthetic gas scavenging disposal systems
Terminal units for medical gas pipeline systems
Part 1: Terminal units for use with compressed medical gases and vacuum
Part 2: Terminal units for anaesthetic gas scavenging systems
Pressure regulators for use with medical gases
Part 1: Pressure regulators and pressure regulators with flow-metering devices
Part 2: Manifold and line pressure regulators
Part 3: Pressure regulators integrated with cylinder valves
Part 4: Low-pressure regulators
Anaesthetic and respiratory equipment: Compatibility with oxygen
Flow-metering devices for connection to terminal units of medical gas pipeline systems
Oxygen concentrator supply systems for use with medical gas pipeline systems
High-pressure flexible connections for use with medical gas systems
Rail systems for supporting medical equipment
Medical gas systems: Systems for evacuation of plume generated by medical devices

ISO 5358:1992
ISO 5359:2008,
Amd 1:2011
ISO 5360:2012
ISO 8835-7:2011
ISO 11195:1995
ISO/TS 18835:2004
ISO 80601-2-13:2011*
ISO 80601-2-55:2011
ISO 11197:2004
ISO 7396-1:2007
ISO 7396-2:2007
ISO 9170-1:2008
ISO 9170-2:2008
ISO 10524-1:2006
ISO 10524-2:2005
ISO 10524-3:2005
ISO 10524-4:2008
ISO 15001:2010
ISO 15002:2008
ISO 10083:2006
ISO 21969:2009
ISO 19054:2005
ISO/WD 16571

From http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_tc_browse.htm?commid=51986&published=on
*Replaces IEC 60601-2-13:2003+A1:2006.
Replaces ISO 21647.
Amd, amendment; TS, technical specification.

of technology. Although obsolescence is difficult to


define, a gas machine that has been in operation for more
than two decades should be retired, because it will be
missing many important safeguards. Failure to retire an
outdated machine can significantly jeopardize the safety
of the patient, and it can create liability issues for the
anesthesia provider and the institution. Unfortunately,
no legal mechanism exists to ensure that such equipment
is not used.
In 1990 CEN began working on a standards project
entitled Anesthetic Workstations and Their Modules:
Essential Requirements. The Anesthetic and Respiratory Devices Committee of ISO was actively involved in
the development of this European standard, which established the important safety and performance requirements for anesthetic workstations, or anesthetizing
locations, as they are known in the United States. The
standard, EN 740:1999, outlined the complete requirements for individual modules that together constitute a
complete anesthetic workstation (i.e., anesthesia ventilator, breathing system, scavenging system, vaporizers,

monitors, and alarm systems). Here, the goal was not to


specify a universal world anesthesia machine but rather to
ensure that each component used clinically meets minimum, specific, identifiable requirements. Subsequently, a
version of this standard became ISO 60601-2-13:2003,
which became ISO/IEC 80601-2-13:2011, rewritten
under the third edition of the general standard.28
Each of these standards applies the same requirements
to both the workstation as a whole and the individual
modules. These standards cover environmental conditions, electrical shock hazards, mechanical hazards, excessive or unwanted radiation, and excessive temperature;
they also set requirements for construction as well as for
minimum accuracy. Although these standards recognize
the practice standards both in the United States and in
other countries, they do expect minimum monitoring
configurations. Additionally, they require that certain
performance standards be met for those elements that are
present.
Hazards inherent in the intended physiologic function
of an anesthetic workstation and its individual components

710

PART VII Safety, Standards, and Quality


Pressure regulators
(ISO 10524-1)
Gas cylinders
Pin indexed
(ISO 407)

Airway gas module


(IEC/ISO 80601-2-55)
Electronically controlled
vaporizer with cassette

Terminal
units
(ISO 9170-1)

Pipeline (primary
and secondary)
systems
(ISO 7396-1)

Compressed
gas

Patient monitoring
modules
(various standards)

Vacuum

Integrated suction
(ISO 10079-3)

Terminal
units
(ISO 9170-2)

Anesthesia gas
scavenging
system
(ISO 7396-2)

IEC/ISO 80601-2-13
Includes requirements for the gas devlivery system,
breathing system, gas scavenging system,
vapor delivery system, ventilator,
monitoring equipment,
alarm system, protection devices

Others (not shown):


ISO 5362 (reservoir bag)
ISO 5367 (breathing tubes)
ISO 5359 (low pressure hose
assemblies e.g., DISS, NIST)

FIGURE 34-4 n Selected standardized portions of the anesthesia workstation and its connections. DISS, diameter index safety
system; IEC, International Electrotechnical Commission; ISO, International Organization for Standardization; NIST, National Organization for Standards and Technology. (Courtesy GE Healthcare, Waukesha, WI.)

within the scope of ISO/IEC 80601-2-13:2011 are not


covered by specific requirements therein, and it is not
applicable to any anesthetic workstation intended for use
with flammable anesthetic agents.
Respiratory Gas Monitors. The latest international
standard for respiratory gas monitors is ISO 80601-255:2011, prepared by ISO/IEC Joint Working Group 6
of TC 121 SC/1, and it specifies the particular requirements for the basic safety and essential performance of a
respiratory gas monitor (RGM) intended for continuous
operation for use with a patient.29 It is not applicable to
an RGM intended for use with flammable anesthetic
agents. It cancels and replaces previous international
standard ISO 21647, which had combined the previous
standards for anesthetic gas monitors (ISO 11196:1995),
carbon dioxide monitors (ISO 7767:1997), and oxygen
monitors (ISO 9918:1993) into a single standard. ISO
80601-2-55:2011 was the first RGM standard to be harmonized with the third edition of the general standard.
Additional reporting requirements have been added to
the standard that impact test requirements. Separate
requirements as applicable are specified for diverting and
nondiverting respiratory gas monitors. These include
disclosure of the minimum sampling flow rate for a
diverting gas monitor. Minimum accuracy using the test
procedure described in the standard is specified in the
standard and is shown in Table 34-9.
Note that previous standards may have used different
units of measure (e.g., partial pressure for carbon dioxide) to
express accuracy, and it was the intent of the RGM standard
to use consistent units for all of the gases. The accuracy of
each gas is expressed as an offset error at zero with a slope
error specified in the table. For example, at 5% carbon dioxide (38 mm Hg at sea level pressure of 760 mm Hg), the

measurement accuracy requirement in the form of a line


described by mx + b (where m is the slope and b is the
intercept) would be calculated as ([0.43 100] + [8 100]
[0.05]), or 0.0083 vol% or 6.3 mm Hg (0.0083 760).
Additionally, there are test requirements for drift, total
system response and rise time, and gas interferences with
the appropriate gas mixtures listed for each type of gas
monitor. The standard attempts not to be design restrictive. However, for the sake of safety, connector requirements exist for the exhaust and input and restrictions on
flow direction as well as for alarm condition priority
requirements.
In addition to this international standard, the requirements and guidelines from numerous clinical American
and other societiesAssociation of Anaesthetists of
Great Britain and Ireland (AAGBI), ASA, American College of Emergency Physicians (ACEP), American Association for Respiratory Care (AARC), American Heart
Association (AHA), American Society for Gatrointestinal
Endoscopy (ASGE), European Resuscitation Council
(ERC), and Society of Critical Care Medicine (SCCM)
and government bodies (e.g., New York, New Jersey,
North Carolina, and Ohio) with respect to the use of carbon dioxide monitors grows every year. This often
includes specific requirements for continuous carbon
dioxide monitoring.
Pulse Oximeters. The latest international standard for
pulse oximeters is ISO 80601-2-61:2011, prepared by a
joint working group of TC 121 SC 3, and it cancels and
replaces ISO 9919:2005 and has been harmonized with
the third edition of the general standard.30 It specifies the
basic safety and essential performance of pulse oximeter
equipment intended for use on humans, including the
pulse oximeter monitor, pulse oximeter probe, and any

34 Standards and Regulatory Considerations

711

TABLE 34-8 K
 ey Differences Between Selected U.S. Anesthesia Machine/Workstations: Standards
from 1979 to the Present
ANSI Z-79.8* (1979)15

ASTM F1850-00 (2005)27

Key changes

First standard for anesthesia machines, structured


as a requirements list for machine components
(59 pages)

Cancels or replaces

NA

F1850 (anesthesia workstation; 32 pages)


structured as a particular standard of IEC
60601-1 second edition; includes data
interface requirements for workstation,
interfaced infusion pump, and automated
anesthesia record keeper (AARK)
F1850 replaced F1161 (1988, reapproved
1994),26 which replaced ANSI Z-79.8
Selected additions or changes from Z-79.8
64.3 Each flow control is next to a flow
indicator.
64.5 Profile of oxygen flow control knob is
physically distinguishable.
65.4 Oxygen flow indicator is to the right most
extremity of a bank of flow indicators.
76 An auxiliary oxygen flowmeter is strongly
recommended.
51.9.3.3 Maximum limited pressure is
protected during intended use and singlefault conditions.
Various connection requirements were added
for patient connection port, exhaust port,
reservoir and other ports, Y-piece, and
exhaust valve.

Selected requirements
Anesthetic gas delivery
system, breathing
system, and ventilator

Anesthesia vapor
delivery system

Patient
monitoring equipment

Scavenging system
Alarm system

Protection module(s)
Other

5.1.3 Pin-indexing system on gas cylinder yokes


5.1.5 Elimination of cross filling between cylinders
6.1.1 Pipeline pressure and cylinder pressure gauges
7.1.2 Pressure regulators to preferentially seek
oxygen from central as opposed to cylinder
supplies
10.1.1 Manually operated single-purpose oxygen
flush valves
11.1.1 Single flowmeter knobs for each gas
11.1.4 Oxygen enters the common manifold
downstream of other gases
14.1.1 Common gas outlet with standard 15 mm
female port to accept connector with coaxial
22-mm male connector designed to prevent
accidental disconnection and misconnection
15.1.3 Pipeline inlet fitting shall be diameterindexed safety systemthreaded body fittings
12.1.8 Vaporizer lockout for multiple vaporizers
13.1 Concentration-calibrated vaporizers
12.1.7 Liquid level indicated, designed to prevent
overfilling
12.1.8 Should use keyed-filling devices
16.1.2 Oxygen analyzer for inadequate oxygen
percentage

4.1.13 A means to convey surplus gas to a system


for its disposal should be provided
16. 1.1 and 16.1.2 Alarms (auditory/visual; O2
supply pressure or inadequate oxygen
percentage)
Various protection measures (e.g., loss of O2
pressure)

68.8 No discharge of liquid anesthetic occurs


from the vaporizer even at maximum fresh
gas flow.
Greater emphasis on patient monitoring
includes:
51.9.4 Exhaled volume
51.10.5 Carbon dioxide
51.11 FiO2
51.12 Oxygen supply pressure
51.13 Hypoxic guard
51.14 Inhaled agents concentration
51.8.2 Volume, gas concentration, and pressure
monitors must be enabled by machine
automatically (no separate power switches).
51.15 SaO2, BP, and ECG (to reflect ASA
minimum monitoring guidelines)
Separate standard (integrated with ISO
80601-2-13)
51.7 Hierarchical alarm prioritization: high,
medium, low
51.8.2.1 Automatic enabling of monitors and
alarms
51.9.3.2 and 51.9.3.3 Maximum pressure limits
on ventilator and anesthesia breathing system
51.13.1 Hypoxia prevention system (O2 >21%)
72 Preoperational checklist must be provided (it
may be electronic, or performed manually by
the user; developed in conjunction with FDA).
78 Data interface
80 Record keeper

*Z79.8 developed by Writing Group on Gas Machine Safety and Performance, chaired by Leslie Rendell-Baker, MD.
ISO 80601-2-13 (2011)28 in the international version, which is harmonized with the third edition of IEC 60601-1; note separate requirements for integrated scavenging systems. Clause numbers from each standard are shown.
Parallax error is possible; a rotameter could be read against wrong scale.
When working in the dark, such as in the x-ray room, the anesthesiologist would often use the sense of touch to determine which knob is
the oxgyen control knob.
ANSI, American National Standards Institute; ASA, American Society of Anesthesiologists; ASTM, American Society for Testing and
Materials; BP, blood pressure; ECG, electrocardiogram; FDA, Food and Drug Administration; IEC, International Electrotechnical Commission; ISO, International Organization for Standardization.

712

PART VII Safety, Standards, and Quality

TABLE 34-9 M
 easurement Accuracy of
Respiratory Gas Monitors*
Measurement Accuracy (Volume
Fraction)
Gas

Slope Error (%)

Offset Error (%)

Halogenated
agent
Carbon dioxide
Nitrous oxide
Oxygen

15

0.2

8
8
2.5

0.43
2.0
2.5

*Modified from ISO 80601-2-55:2011.

probe cable extender. This standard is not applicable to


pulse oximeter equipment intended for use in laboratory
research applications or to oximeters that require a blood
sample from the patient. The intended use of pulse oximeter equipment includes, but is not limited to, the estimation of arterial oxygen hemoglobin saturation and pulse
rate of patients in professional health care institutions
and in the home health care environment.
This standard specifies temperature limits at the tissue
interface and includes reporting requirements for pulse
oximetry (SpO2) over 70% to 100% with Arms, rootmean-squared difference, and reported and accuracy
requirements of functional oxygen saturation as Arms of
less than or equal to 4% SpO2 over the range of 70% to
100%. The accuracy claims are required to be supported
by controlled desaturation studies over the full range with
appropriate testing during motion and/or low perfusion.31 An additional requirement for response time and
alarm condition delay particular to a rapid desaturation is
included. Of interest is a lengthy discussion of the differences between patient simulators of SpO2, none of which
are available; calibrators to test accuracy of the device;
and functional testers that provide a simulated input
using an artificial finger with light sources modulated to
simulate the plethysmographic signals.

Other Standards and Changes


Interoperability
The term interoperability as applied to health care often
means different things to different people. Various
medical device interoperability initiatives are in process.32 Lesh and colleagues33 discuss the challenges of
interoperability:
The concept of interoperability for an increasingly instrumented and computerized healthcare environment
is intuitively appealing, but what does this enticing goal
entail? From a users point of view this can be the ability
of medical devices and people to interact at multiple levels
with seemingly little effort. Underlying this goal is an
enormous amount of complexity, because interoperability
creates dynamic relationships that must be manageable
over time. There are technical, business, regulatory, legal,
and administrative relationships that cumulatively create a
grand challenge.33

There are more than 101,000 devices that fall into one
of 5267 generic device product categories described in 21
C.F.R. Subchapter H, Medical Devices (e.g., an anesthesia machine is described in section 868.5160). The continuum of interoperability based on complexity varies
from physical interoperability, defined as the ability for one
device to connect to or be used with another device and
perform individual functions without alteration of the
individual device, to data/information exchange with
understanding.30 This understanding requires both a
common syntax (messaging standard) and common
semantics (terminology). At present, most medical devices
are not interoperable for reasons that may include:
Lack of incentives or regulatory requirements to
interoperate with other manufacturers devices
Scarcity of accepted medical device interoperability
standards
Slow response of health care sector with respect to
computerization and networking
Liability and regulatory issues33
The potential benefits of medical devices that are
interoperable include improved quality of care and
patient safety, improved clinical decision support, and
closed-loop control of therapies such as medication,
delivery of fluids, and mechanical ventilation.
For example, Arney and colleagues34 demonstrate in a
use case how automatic synchronization of the x-ray
exposure with ventilation eliminates the need to turn off
the ventilator to obtain a radiograph and thereby improves
patient safety by helping to alleviate those circumstances
when an anesthesiologist would turn off the anesthesia
ventilator for a radiograph and forget to turn it back on.
Cortes and colleagues35 propose a design on an interoperable, integrated clinical environment (ICE)compliant
system (see below) for patient-controlled analgesia (PCA)
infusion pumps using integrated decision support and
closed-loop control to detect overmedication using a capnograph and pulse oximeter and to respond to resultant
respiratory depression.
Several consortia working on medical device interoperability include the Medical Device Plug-and-Play
Program (MD PnP; www.mdpnp.org/home.php), the
Continua Health Alliance (www.continuaalliance.org/in
dex.html), and Integrating the Healthcare Enterprise
(IHE; www.ihe.net).
The MD PnP is described as a multidisciplinary,
multi-institutional program committed to simplifying
and standardizing medical device connectivity in support
of improving patient safety and healthcare efficiency.33
Some of their projects include:
Medical Device Clock Errors: A study to address
this issue (e.g., standards) is important given the
general lack of automatic clock setting and time
synchronization in medical devices used in the clinical environment and the potential negative impact
on the electronic medical record (EMR) and analysis of adverse events.
ICE Standard: This set of standards allows comprehensive data acquisition for the EMR and the integration of devices to enable real-time decision
support, safety interlocks, and closed-loop control
through the functions described in a new series of

34 Standards and Regulatory Considerations

standards for the patient-centric integrated clinical environment (ASTM F2761-2009).


MD Fire: This project is intended to promote the
awareness and knowledge of medical device interoperability throughout the medical and healthcare
community.36
Prototype Health Care Intranet for Improved
Health Outcomes: This project was funded by a
$10M National Institutes of Health (NIH) Phase II
Quantum Grant (2010).
Medical Device Interface Data Sheets (MDIDS):
This project is working to create a reference compendium of medical device interface capabilities and
data elements to serve as a reference for SDOs, manufacturers, researchers, and clinical organizations.
Small-Bore Connectors
As explained in the introduction and rationale of ISO
80369-1:2010, in the 1990s, concern grew regarding the
proliferation of medical devices fitted with Luer connectors and the reports of patient death or injury arising
from misconnections that resulted in the inappropriate
delivery of enteral solutions, intrathecal medication, or
compressed gases. Advances in modern medicine have
led to a significant rise in the number of medical devices
connected to patients, including monitoring, diagnostic,
and therapeutic devices. Unfortunately, the tubing of
many of these medical devices is equipped with the same
6% Luer tapered connector as specified in ISO 5941:1996 and ISO 594-2:1998. These medical devices perform a variety of similar, but not interchangeable,
functions and are connected to a variety of different sites
on a patient.
Using compatible connectors in combination with the
proximity of several different connections around a single
patient makes accidental tubing misconnections inevitable. The consequences of such misconnections vary. Serious and usually fatal misconnections include intravenous
(IV) injection of air, IV injection of enteral feeds, and
intrathecal injection of vincristine.37 To solve this problem, new connectors are needed for each functional
application that cannot be interconnected with each other
or with the traditional Luer connector. A JWG of ISO
TC 210 and IEC 62D was formed in 2008 to create and
validate new tubing connectors for breathing system
ancillary connections; driving gases; enteral, urinary, and
cuff-limb inflation; and neuraxial applications, reserving
the traditional Luer connector for vascular access and
hypodermic syringe applications.
ISO 80369, which pertains to small-bore connectors
for liquids and gases in health care applications,38 is being
developed in seven parts; part 1 defines the general
requirements for small-bore connectors, and it is all that
has been published at this writing. The remaining six
parts reflect the division of small-bore connectors by
application areas. They include breathing systems and
driving-gas applications (part 2), enteral applications
(part 3), urethral and urinary applications (part 4), limb
cuff inflation applications (part 5), neuraxial applications
(part 6), and intravascular or hypodermic applications
(part 7, the new Luer standard).

713

These standards will have a profound impact on the


delivery of health care, because many practices and processes will have to change as medical devices begin to
incorporate new tubing connectors. Parts 2, 5, and 6 will
directly impact the delivery of anesthesia.
Alarm Systems
The ISO TC 121 began the development of standardization is this area with the publication of the ISO 9703 series
of standards beginning in 1992. These early standards specified the requirements for alarm signals from anesthetic and
respiratory equipment, the beeping sounds and flashing
lights found on many medical devices today. The next step
in alarm system standardization occurred when a JWG of
ISO TC 121/SC3 and IEC 62A created the collateral standard, IEC 60601-1-8:2003, in the IEC 60601-1 family for
the alarm systems of all medical electrical equipment.
Despite 20 years of published standards for medical
device alarm systems, many problems and challenges
remain with alarm systems used on medical devices today.
In October of 2011, AAMI co-convened with the FDA,
The Joint Commission, ECRI Institute, and American
College of Clinical Engineering a summit to explore the
issues associated with medical alarm system safety. The
summit brought together 300 multidisciplinary stakeholders, and they developed the following seven clarion
themes and priority issues:
1. Deepen all stakeholders understanding of use
environments
2. Improve alarm system management
3. Innovate to improve alarm system integration
4. Reconcile challenges and differences in use
environments
5. Strengthen medical electrical equipment standards
and contracting language to promote success in all
intended use environments
6. Clarify regulatory requirements
7. Share illuminating practices and lessons learned
with all stakeholders39
Acknowledgment
The authors acknowledge Gregory Welyczko of GE
Healthcare (retired), Stand Weitzner, MD, and Mark
Graber of GE Healthcare for their contributions to the
anesthesia equipment standards in Table 34-8.
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PART VII Safety, Standards, and Quality

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