[Federal Register Volume 63, Number 215 (Friday, November 6, 1998)]
[Notices]
[Pages 60178-60189]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29374]
[[Page 60177]]
_______________________________________________________________________
Part VI
Department of Health and Human Services
_______________________________________________________________________
Centers for Disease Control and Prevention
_______________________________________________________________________
Implementation of the Fertility Clinic Success Rate and Certification
Act of 1992; Proposed Model Program for the Certification of Embryo
Laboratories; Notice
Federal Register / Vol. 63, No. 215 / Friday, November 6, 1998 /
Notices
[[Page 60178]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
Implementation of the Fertility Clinic Success Rate and
Certification Act of 1992; Proposed Model Program for the Certification
of Embryo Laboratories
AGENCY: Centers for Disease Control and Prevention (CDC), Department of
Health and Human Services (HHS).
ACTION: Notice and request for comments.
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SUMMARY: The Fertility Clinic Success Rate and Certification Act of
1992 (Pub. L. 102-493, 42 U.S.C. 263a-1 et seq.) requires that the
Secretary, HHS, through CDC, develop a model program for the
certification of embryo laboratories, to be carried out voluntarily by
interested States. The model certification program is to be developed
in consultation with appropriate consumer groups and professional
organizations with knowledge and expertise in assisted reproductive
technology.
This notice sets forth a description of the proposed model
certification program, including the proposed definitions,
administrative requirements, and embryo laboratory standards.
Accordingly, CDC solicits comments on the proposed model certification
program and reserves the right to revise the program based upon the
comments it receives.
DATES: To assure consideration, written comments on the proposed model
certification program for embryo laboratories as described in this
notice must be received at the address indicated below on or before
January 5, 1999.
ADDRESSES: Address all written comments to: Model Certification
Program--Federal Register Notice, Centers for Disease Control and
Prevention, Mail Stop K-66, 4770 Buford Highway N.E., Atlanta, Georgia
30341-3724.
Due to staffing and resourcing limitations, we cannot accept
facsimile (FAX) copies of comments nor can we accept comments by
telephone.
FOR FURTHER INFORMATION CONTACT:
Nancy Anderson or Carol Cook, Division of Laboratory Systems, telephone
(770) 488-8047 or (770) 488-8029.
SUPPLEMENTARY INFORMATION:
Introduction
The Fertility Clinic Success Rate and Certification Act of 1992
(FCSRCA), Public Law 102-493 (42 U.S.C. 263a-1 et seq.), was intended
to provide the public with comparable information concerning the
effectiveness of infertility services and to assure the quality of such
services by providing for the certification of embryo laboratories.
Section 2 of the statute requires that the Secretary, HHS, through
CDC, define pregnancy success rates, and seek public comment on the
proposed definitions. In addition, Section 2 requires each assisted
reproductive technology (ART) program to annually report its pregnancy
success rates to CDC, along with the identity of each embryo laboratory
used by the program, and whether the laboratory is certified under
Section 3 or has applied for such certification. Section 2 was
addressed in a Federal Register notice published on August 26, 1997 (62
FR 45259).
Section 3(a) of the FCSRCA requires that the CDC ``develop a model
program for the certification of embryo laboratories . . . to be
carried out by the States.'' In developing the model certification
program, CDC is to consult with ``appropriate consumer and professional
organizations with expertise in using, providing, and evaluating
professional services and embryo laboratories associated with assisted
reproductive technology programs.''
Section 3(b) lists State official who are to received a description
of the model certification program, and requires that the Secretary
encourage States to adopt such a program.
Section 3(c) includes the requirements for administration of the
certification program by the States, with provisions for the inspection
and certification of embryo laboratories by States or approved
accreditation organizations, and the requirement for application to the
State by an embryo laboratory that seeks certification.
Section 3(d) specifies the embryo laboratory standards that are to
be in the model certification program. These include a standard to
assure consistent performance of laboratory procedures; a standard for
a quality assurance and quality control program; standards for the
maintenance of all laboratory records (including laboratory tests and
procedures performed, as well as personnel and equipment records); and
a standard for personnel qualifications.
Section 3(e) includes provisions for a State to adopt the model
certification program if it applies to the Secretary, and is approved,
and Section 3(f) allows for the use of accreditation organizations,
approved under the requirements described in Section 4, to inspect and
certify embryo laboratories in States that have adopted the program.
Section 3(g) requires that States which qualify to adopt the model
certification program conduct embryo laboratory inspections to
determine if the laboratories meet the requirements of the program.
Section 3(g) also requires the Secretary to seek public comment on the
conditions under which announced inspections may be conducted without
diminishing the likelihood of discovering deficiencies in the
operations of an embryo laboratory. In addition, inspection results
(including deficiencies and any subsequent corrections to those
deficiencies) are to be reported and made available to the public.
Section 3(h) provides for the Secretary to conduct validation
inspections of embryo laboratories certified by a State or an approved
accreditation organization to determines if the laboratories are being
operated in accordance with the standards in the model certification
program. If a validation survey demonstrates that an embryo laboratory
is not in compliance with such standards, the statute specifies
requirements for notification of the State, or as applicable, the
accreditation organization. A subsequent investigation and inspection
of additional certified embryo laboratories are to be conducted to
determine if the State or accreditation organization is reliably
identifying laboratory deficiencies. The Secretary may revoke the
approval of the State certification program or accreditation
organization if requirements applicable to the program are not being
met.
Section 3(i) limits the Secretary is developing the model
certification program, and the States in adopting such program, from
establishing any regulation, standard, or requirement that has the
effect of exercising supervision or control over the practice of
medicine in ART programs.
Section 3(j) states that the Secretary may define the term of the
certification issued by a State or an accreditation organization in a
State, through the public comment process, and provides for application
for recertification to be submitted when there is a change in ownership
or administration of a certified embryo laboratory.
Section 4 calls for the Secretary, through CDC, to promulgate
criteria and procedures for the approval and use of accreditation
organizations to inspect and certify embryo laboratories in States
which have adopted the model certification program, as well as in
States which have not adopted the program. The section also includes
[[Page 60179]]
provisions for annual evaluation of approved accreditation
organizations by the Secretary, through the inspection of a
representative sample of accredited embryo laboratories and other such
appropriate means.
Section 5 specifies the conditions under which a certification
issued by a State or an accreditation organization shall be revoked or
suspended, and the effect that such revocation or suspension would
impose on the certification and application for recertification of the
laboratory.
Section 6 mandates that the Secretary, through CDC, annually
publish pregnancy success rates as reported by ART programs (Section
2); the names of ART programs that fail to report pregnancy success
rates; the identity and certification status of each embryo laboratory
located in a State which has adopted the model certification program;
the identity of each embryo laboratory in a State which has not adopted
the certification program and which has been certified by an approved
accreditation organization; and in the case of an embryo laboratory
which is not certified, whether the laboratory has applied for
certification. The annual publication is to be distributed to States
and the public. This section was also addressed in the previously
mentioned Federal Egister notice published on August 26, 1997 (62 FR
45259). The first report, 1995 Assisted Reproductive Technology Success
Rates: National Summary and Fertility Clinic Reports, was published in
December 1997. Copies of the report may be obtained by contacting
RESOLVE, a national consumer organization helping infertile couples and
individuals, at 1-888-299-1585 or via the Internet at www.resolve.org.
Section 7 authorizes the Secretary to charge sufficient fees to
cover the cost of administering the FCSRCA and authorizes States
adopting the certification program to charge sufficient fees to cover
the cost of administering their program.
Section 8 includes a definition of assisted reproductive technology
and provides for seeking public comment on any proposed expansion of
the definition.
Actions Taken To Develop the Proposed Model Certification Program
In accordance with the FCSRCA, CDC consulted with individuals,
professional organizations and consumer groups with expertise and
interest in ART throughout the development of the proposed model
certification program for embryo laboratories. Consultation was
provided by organizations representing reproductive medicine, including
the American Society for Reproductive Medicine (ASRM) and the Society
for Assisted Reproductive Technology, laboratory organizations such as
the College of American Pathologists (CAP) and the American Association
of Bioanalysts, and a consumer group that serves to educate the public
on infertility diagnosis and treatment (RESOLVE). CDC also worked
closely with several State programs throughout the process to ensure
that the proposed model certification program, when finalized, could
easily be adopted and implemented by interested States, and sought
input from Federal agencies with regulatory responsibilities related to
laboratory practice, tissue banking and ART.
A useful example in developing the proposed model certification
program was the voluntary accreditation program for reproductive
laboratories that is currently administered by the CAP. This program
was developed jointly between the CAP and the ASRM, and has been in
existence since 1993. More than one third of the embryo laboratories
associated with ART programs in the United States currently participate
in this voluntary program. As CDC began drafting the proposed model
certification program, an initial step was to meet with representatives
from the CAP to gather information on the CAP/ASRM Reproductive
Laboratory Accreditation Program, including the laboratory standards
and inspection checklists used by CAP inspectors and reproductive
laboratories. CDC also used a variety of guidelines and standards from
other professional organizations, State, Federal, and international
programs as resources (see References), and made a number of site
visits to embryo laboratories to observe the daily operation of these
facilities.
Between November 1996 and August 1997, CDC held several work
sessions with technical consultants to obtain input on specific issues
related to the embryo laboratory and the proposed model certification
program, including personnel qualifications and responsibilities,
quality assurance and quality control (quality management),
recordkeeping, specific definitions as they apply to the model
certification program, and State administration of the program. The
individuals who participated in these work sessions were asked to
provide consultation because of their expertise and interest in ART
laboratory procedures, or experience with clinical laboratory testing.
The input provided by each consultant was used by CDC to assist in its
internal deliberations to develop a practical and effective model
certification program for embryo laboratories. No group consensus was
sought at any of the sessions.
On-going Review of Embryo Laboratories
In passing the FCSRCA, Congress anticipated that the cost of
Federal and State monitoring and oversight of embryo laboratories would
be covered by the fees they pay. Section 7 of the statute provides for
the collection of sufficient fees from participating embryo
laboratories to cover these costs. However, participation by embryo
laboratories is voluntary; laboratories not willing to pay these fees
would not be limited in their ability to operate.
CDC plans to implement oversight and monitoring under the FCSRCA to
the extent the roughly 350 embryo laboratories are willing to
voluntarily pay sufficient fees to cover oversight costs. At this time,
embryo laboratories have not indicated they would opt into such an
oversight program. CDC will continue to review embryo laboratories'
interest in, and willingness to pay for, a formalized Federal oversight
program, and adjust CDC's plans accordingly.
CDC has, however, developed these proposed model certification
standards, incorporating the definitions, administrative requirements
and laboratory standards that are called for in the FCSRCA, and is
publishing them to provide an opportunity for public comment. The model
certification program will be revised as necessary, based on these
comments, published as a final notice in the Federal Register, and the
final model will be distributed to State officials and health
authorities as outlined in the statute.
At this time, CDC will defer implementation of the approval of
state certification programs or accreditation organizations. In
addition, Federal validation inspections of embryo laboratories
certified by States adopting the model or accredited by an
accreditation program for embryo laboratories will also be deferred
until a sufficient number of laboratories are willing to opt into a
self-supporting system. In this proposed model, implementation of these
activities would be the responsibility of States that choose to adopt
the model certification program.
To summarize, CDC proposes a model certification process for embryo
laboratories performing assisted reproductive technology (ART). In
developing this proposal, we have carefully reviewed an existing
program, the CAP/ASRM Reproductive Laboratory Accreditation Program
[[Page 60180]]
(RLAP) which was developed by the professional community and provides
oversight of embryo laboratories affiliated with ART programs and
clinics. We have also taken note that there are existing voluntary
programs in other areas of laboratory practice, such as the American
Society of Clinical Pathologists and the American Board of Bioanalysts'
laboratory personnel certification programs, that have had a beneficial
impact on laboratory quality, without Federal oversight.
As mentioned previously in this preamble, the CAP/ASRM's RLAP
provided the basis for many of the laboratory standards specified in
the proposed model. We believe that this existing ART laboratory
accreditation program likely will meet the standards we have proposed
in the model and will provide an excellent resource for States which
wish to develop their own certification program. In addition, other
professional organizations have expressed an interest in establishing
and/or adopting standards for the embryo laboratory; the proposed
certification process should benefit those other groups.
While the model certification program for embryo laboratories
proposed in this model does not provide for a Federal oversight role
until a sufficient number of laboratories would opt into a self-
supporting system, we welcome public comment on the need, desirability
and specific benefits of Federal oversight.
Request for Comments on the Proposed Model Certification Program
Written comments on any aspect of the proposed model certification
program included in this notice may be submitted to CDC during the
public comment period at the address specified for receipt of comments.
In addition, the FCSRCA requires the Secretary to facilitate public
comment on specific aspects of the model certification program and the
definitions as they relate to the model. To ensure appropriate
consideration by commenters, the following issues are highlighted:
Based on the comments received during the previously
mentioned work sessions with technical consultants, the proposed
model's definitions for ``assisted reproductive technology'' and
``embryo laboratory'', have been elaborated from the definitions
specified in the FCSRCA. The issue is whether the revised
definitions are appropriate and accurate for use in the model
certification program.
The proposed model permits announced initial and
routine inspections and unannounced inspections for complaint
investigations. The issues are under what circumstances should
announced inspections be permitted so as not to diminish the
likelihood of discovering deficiencies in the operation of an embryo
laboratory, and whether there are circumstances that should require
unannounced inspections.
The proposed model specifies a 2-year term for embryo
laboratory certification. The issue is whether this is an
appropriate period of time for the term of certification of a
laboratory (i.e., renew biennially).
In addition, we are interested in receiving comments on the
following issue which is not specifically addressed in the proposed
model certification program but may be considered for inclusion in the
finalized model:
Proficiency testing (PT) currently available for the
embryo laboratory is limited to determining whether culture media
samples provided by the PT program are suitable for in vitro mouse
embryo culture. While the performance of PT is not required in the
proposed model, the model's standards do require a laboratory to
perform quality control procedures to monitor the reliability of the
ART procedures performed (including culture media checks). Equipment
and instrument maintenance and function checks are also required to
ensure their adequate performance. In addition, the laboratory must
track and evaluate procedural outcomes such as fertilization rates,
cleavage rates and embryo quality as a means of monitoring the
quality of the procedures and services provided by the laboratory.
The issue is whether these standards provide a sufficient means for
monitoring laboratory performance or if a standard requiring PT
should be included in the model.
Organization of Proposed Model Certification Program
This notice describes the proposed model certification program for
embryo laboratories and includes the proposed definitions (Part I),
proposed administrative requirements (Part II), and proposed embryo
laboratory standards (Part III). References are also provided as an
addendum to this notice for background and educational purposes.
Dated: October 28, 1998.
Jeffrey P. Koplan,
Director, Centers for Disease Control and Prevention (CDC).
PROPOSED MODEL CERTIFICATION PROGRAM FOR EMBRYO LABORATORIES
Contents
Part I. Definitions
Part II. Administrative Requirements
Part III. Embryo Laboratory Standards
Addendum References
Part I. Definitions
Accredited institution. A school or program which----
(a) Admits as a regular student only persons having a certificate
of graduation from a school providing secondary education, or the
recognized equivalent of such certificate;
(b) Is legally authorized within the State to provide a program of
education beyond secondary education;
(c) Provides an educational program for which it awards a
bachelor's degree or provides not less than a 2-year program which is
acceptable toward such a degree, or provides an educational program for
which it awards a master's or doctoral degree; and
(d) Is accredited by a nationally recognized accrediting agency or
association.
This definition includes any foreign institution of higher
education that HHS or its designee determines meets substantially
equivalent requirements.
Approved accreditation organization. An accreditation organization
that has formally applied for and received the State's approval based
on the organization's compliance with this model certification program
and other requirements as specified by the State.
ART. Assisted reproductive technology.
Assisted hatching. A micromanipulation technique which involves
making a small opening in the zona wall of the embryo to enhance
implantation.
Assisted reproductive technology. All clinical treatments and
laboratory procedures which include the handling of human oocytes and
sperm, or embryos, with the intent of establishing a pregnancy. This
includes, but is not limited to, in vitro fertilization, gamete
intrafallopian transfer, zygote intrafallopian transfer, embryo
cryopreservation, oocyte or embryo donation, and gestational surrogacy.
Assisted reproductive technology cycle. Any cycle in which (1) ART
has been used, (2) in which the woman has undergone ovarian stimulation
or monitoring with the intent of undergoing ART, (3) a woman has
donated oocytes, or (4) in the case of cryopreserved embryos, in which
embryos have been thawed with the intent of transfer. ART cycles can be
stimulated (use of ovulation induction) or unstimulated (natural
cycle).
Assisted reproductive technology laboratory procedures. All
laboratory procedures for handling and processing of human oocytes and
sperm, or embryos, with the intent of establishing a pregnancy. These
procedures include, but are not limited to, the examination of
follicular aspirates, oocyte classification, sperm preparation, oocyte
insemination, assessment of fertilization, assessment of embryo
[[Page 60181]]
development, preparation of embryos for embryo transfer, and
cryopreservation of specimens.
Assisted reproductive technology program or clinic. A legal entity
practicing under State law, recognizable to the consumer, that provides
ART to couples who have experienced infertility or are undergoing ART
for other reasons. This can be an individual physician or a group of
physicians who practice together, and share resources and liability.
Authorized person. An individual authorized under State law to
order ART procedures.
CDC. The Centers for Disease Control and Prevention.
CLIA. The Clinical Laboratory Improvement Amendments of 1988.
Certification. The certification of an embryo laboratory by a State
certification program or through accreditation by an approved
accreditation organization.
Certification program. The model certification program for embryo
laboratories described in this notice or a State certification program
for embryo laboratories which meets or exceeds the requirements of the
model certification program.
Cryopreservation. A technique to preserve biologic material through
freezing.
Doctoral scientist. An individual holding an earned doctoral degree
in a chemical, physical, biological or medical laboratory science from
an accredited institution. As defined here, doctoral scientist also
includes individuals holding an earned doctoral degree in veterinary
medicine.
Embryo. The normal (2 pronuclei) fertilized egg that has undergone
one or more divisions.
Embryo laboratory. A facility in which human oocytes and sperm, or
embryos, are subject to ART laboratory procedures.
Embryo transfer. Introduction of an embryo(s) into a woman's uterus
after in vitro fertilization.
Fertilization. The penetration of the egg by the sperm and fusion
of genetic materials to result in the development of a fertilized egg
(or zygote).
Gamete intrafallopian transfer. An ART procedure that involves
removing eggs from the woman's ovary, combining them with sperm, and
immediately injecting the eggs and sperm into the fallopian tube.
Fertilization takes place inside the fallopian tube.
HHS. The U.S. Department of Health and Human Services, or its
designee.
Intracytoplasmic sperm injection. The placement of a single sperm
into the ooplasm of an oocyte by micro-operative techniques.
In vitro fertilization. A method of assisted reproduction that
involves removing eggs from a woman's ovaries, combining them with
sperm in the laboratory and, if fertilized, replacing the resulting
embryo(s) into the woman's uterus.
Laboratory. Unless otherwise specified in this notice, means embryo
laboratory.
Micromanipulation. Microtechniques such as intracytoplasmic sperm
injection and assisted hatching commonly used to overcome fertilization
disorders.
Physician. An individual with a doctor of medicine or doctor of
osteopathy degree who is licensed by the State to practice medicine or
osteopathy within the State in which the embryo laboratory is located.
Procedural outcome. The outcome of the assisted reproductive
technology laboratory procedure performed e.g., fertilization
assessment--the presence of two pronuclei in the ooplasm.
Oocyte. The female reproductive cell, also called an egg.
Specimen. Human biologic material (includes human reproductive
tissue such as oocytes, sperm, zygotes and embryos).
Sperm. The male reproduction cell that has completed the process of
meiosis and morphological differentiation.
State. Includes, for purposes of this model certification program,
each of the 50 States, the District of Columbia, the Commonwealth of
Puerto Rico, the Virgin Islands, and other territories of the United
States, and a political subdivision of a State where the State, acting
pursuant to State law, has expressly delegated powers to the political
subdivision sufficient to authorize the political subdivision to act
for the State in enforcing requirements equal to or more stringent than
the model certification program.
Zygote. A normal (2 pronuclei) fertilized egg before cell division
begins.
Zygote intrafallopian transfer. Eggs are collected and fertilized,
and the resulting zygote is then transferred to the fallopian tube.
Part II. Administrative Requirements
A. Overview
The certification program for embryo laboratories is a model
program developed by the Centers for Disease Control and Prevention
(CDC) in accordance with Pub. L. 102-493 (42 U.S.C. 263a-1 et seq.) and
is to be administered by interested States.
B. Requirements for State Administration of the Model
Certification Program for Embryo Laboratories. The State may adopt
and administer the model certification program for embryo laboratories
described in this notice of administer a State certification program
for embryo laboratories that meets or exceeds the requirements of the
model certification program, and must, at a minimum, meet the following
provisions--
1. Certification Under State Programs. A State may qualify to adopt
and administer the model certification program if the State submits an
attestation to CDC (contact to be provided in final notice) providing--
a. Assurances that the certification program for embryo
laboratories administered by the State meets or exceeds the
requirements of the model certification program specified in this
notice.
b. An agreement that in administering the certification program, a
State will not establish any regulation, standard, or requirement which
has the effect of exercising supervision or control over the practice
of medicine in assisted reproductive technology programs or clinics.
c. An agreement that the term of State certification/
recertification issued to an embryo laboratory is for a period of not
more than two years.
d. An agreement to investigate, when appropriate and to the extent
necessary, complaints received about an embryo laboratory certified
under the State's program.
e. An agreement to annually report to CDC, (contact to be provided
in final notice) the identity and certification status of each embryo
laboratory in the State as well as any such laboratory which has
applied for certification, and the assisted reproductive technology
programs, or clinics with which each embryo laboratory is associated,
for annual publication by CDC.
f. Information about any proposed use and approval and revocation
of approval of accreditation organizations in accordance with paragraph
2. and 5. of this section.
g. An agreement to make such reports as the Secretary of the
Department of Health and Human Services (through CDC) may require.
2. Use and Approval of Accreditation Organizations. Accreditation
organizations approved by the State may be used to inspect and accredit
embryo laboratories for the purpose of State certification and such
accreditation shall constitute certification. The criteria and
procedures used by the
[[Page 60182]]
State to approve accreditation organizations must include, at a
minimum, the following:
a. The accreditation organization must provide assurances
satisfactory to the State that its standards and requirements for
accreditation of embryo laboratories meet or exceed the requirements of
the certification program;
b. The accreditation organization must, at a minimum, conduct
inspections of embryo laboratories in accordance with the requirements
under paragraph 4. of this section which includes making available to
the public, upon request, the specific findings (with any explanatory
information required to interpret the findings), including deficiencies
identified in an inspection, and any subsequent corrections to those
deficiencies, no later than 60 days after the date of the inspection;
c. The accreditation organization must agree to revoke or suspend a
laboratory's accreditation for one year, if the accreditation
organization finds, on the basis of inspections, that the owner or
operator of the laboratory, or any employee of the laboratory--
A. Has been guilty of misrepresentation in obtaining the
accreditation.
B. Has failed to comply with any standards of the accreditation
program.
C. Has refused a request of the accreditation organization or State
for permission to inspect the laboratory, its operations, and records;
and
d. The accreditation organization must agree to submit such reports
and maintain such records as the State, or HHS, may require, to
include, but not be limited to, the following:
i. Notification to the State of each newly accredited embryo
laboratory within the State within 30 days of the laboratory obtaining
accreditation;
ii. Notification to the State of any embryo laboratory within the
State that has its accreditation denied, suspended, withdrawn or
revoked, or that has had any other adverse action taken against it by
the accreditation organization within 30 days of the action taken;
iii. Notification to the State within 10 days of a deficiency
identified in any accredited embryo laboratory within the State where
the deficiency poses an immediate jeopardy to the laboratory's patients
or a hazard to the general public;
iv. Notification to the State if the accreditation organization
finds, on the basis of inspections, that the owner or operator of the
laboratory, or any employee of the laboratory--
A. Has been guilty of misrepresentation in obtaining the
accreditation.
B. Has failed to comply with any standards of the accreditation
program.
C. Has refused a request of the accreditation organization for
permission to inspect the laboratory, its operations, and records;
v. Provide inspection schedules as requested by the State for the
purposes of conducting onsite validation inspections of laboratories;
and
vi. Provide the State written notification at least 30 days in
advance of the effective date of any proposed changes in its
requirements.
3. Embryo Laboratory Application Requirements. The State must
provide for the submission of an application to the State by an embryo
laboratory requesting certification, in such form as may be specified
by the State. Such an application must include the following:
a. Assurance satisfactory to the State that the embryo laboratory
will be operated in accordance with the standards of the certification
program;
b. An agreement by the embryo laboratory to--
i. Annually report to the State the assisted reproductive
technology programs or clinics with which the laboratory is associated.
ii. Submit changes in the ownership or the administration of the
laboratory to the State within 30 days of the change.
iii. Permit the State to conduct onsite inspections including, as
applicable, initial, routine, validation and complaint inspections,
upon presentation of identification to the owner, operator, or agent in
charge of the laboratory, during the laboratory's regular hours of
operation to determine compliance with the certification program.
iv. Permit the State to have access to all facilities, equipment,
materials, records, and information which the State requires to
determine if the laboratory is being operated in accordance with the
standards of the certification program.
v. Permit the State to copy any material, record, or information
inspected, or submit such, upon request by the State.
vi. Permit the State to make available, upon request, to the
public, the laboratory's specific inspection findings (with any
explanatory information required to interpret the findings), including
deficiencies identified in an inspection, and any subsequent
corrections to those deficiencies;
c. If the State allows certification of an embryo laboratory on the
basis of the laboratory's accreditation by an approved accreditation
organization (i.e., issues a certificate of accreditation), the
laboratory must, in addition to the requirements of subparagraphs 3.a.
and 3.b. of this section--
i. Submit proof of current accreditation;
ii. Permit the accreditation organization to have access to all
facilities, equipment, materials, records, and information which the
accreditation organization requires to determine if the laboratory is
being operated in accordance with the standards of the accreditation
organization program;
iii. permit the accreditation organization to copy any material,
record, or information inspected, or submit such, upon request by the
accreditation organization;
iv. Permit the accreditation organization to make available, upon
request, to the public, the laboratory's specific inspection findings
(with any explanatory information required to interpret the findings),
including deficiencies identified in an inspection, and any subsequent
corrections to those deficiencies; and
v. Agree to authorize the accreditation organization to submit to
the State or HHS such laboratory-specific information or reports as the
State or HHS may require; and
d. Such other information, agreements and assurances as the State
finds necessary.
4. Initial, Routine and Complaint Inspections. Inspections must be
conducted to determine if embryo laboratories applying for or renewing
their certification meet the requirements of the certification program.
In addition, inspections may be performed as part of the State's
investigation of complaints received about a certified embryo
laboratory. The inspections may be carried out by the State or, as
applicable, by an accreditation organization approved by the State in
accordance with paragraph 2. of this section.
a. Initial inspections for embryo laboratory certification must be
performed during the laboratory's regular hours of operation and may be
announced. Initial inspections are performed when the laboratory
applies for certification and may be performed for recertification
after the laboratory has had a change in ownership or administration.
b. Routine inspections for renewal of the laboratory's
certification must be performed biennially, during the laboratory's
regular hours of operation and may be announced.
[[Page 60183]]
c. Inspections to investigate complaints received by the State
about a laboratory may be performed unannounced, during the
laboratory's regular hours of operation.
d. Inspection of a laboratory may be made only upon the
presentation of identification to the owner, operator, or agent in
charge of the laboratory being inspected.
e. In conducting an inspection, the State or approved accreditation
organization must have access to all facilities, equipment, materials,
records, and information which the State or approved accreditation
organization requires to determine if the laboratory is being operated
in accordance with the standards of the certification program.
f. The State or approved accreditation organization may copy any
material, record, or information inspected or require it to be
submitted to the State or, as applicable, to the approved accreditation
organization.
g. The specific findings (with any explanatory information required
to interpret the findings), including deficiencies identified in an
inspection, and any subsequent corrections to those deficiencies must
be made available to the public upon request beginning no later than 60
days after the date of the inspection.
5. Validation Inspections. The State must annually evaluate the
performance of each approved accreditation organization by performing
validation inspections of a sufficient number of embryo laboratories
within the State accredited by the organization, to allow a reasonable
estimate of the performance of such organization.
a. The State may enter and inspect, during regular hours of
operation, embryo laboratories which have been accredited by an
approved accreditation organization for the purpose of determining
whether the laboratory is being operated in accordance with the
standards of the certification program.
b. A validation inspection of a laboratory may be announced and be
made only upon the presentation of identification to the owner,
operator, or agent in charge of the laboratory being inspected.
c. In conducting a validation inspection, the State must have
access to all facilities, equipment, materials, records, and
information which the State requires to determine if the laboratory is
being operated in accordance with the standards of the certification
program.
d. The State may copy any material, record, or information
inspected or require it to be submitted to the State.
e. If the State determines as a result of a validation inspection
that the embryo laboratory is not in compliance with the standards of
the certification program, the State must--
i. Notify the accreditation organization which accredited the
laboratory.
ii. Make available to the public the inspection findings (with any
explanatory information required to interpret the findings), including
deficiencies identified in the inspection, and any subsequent
corrections to those deficiencies.
iii. Conduct additional inspections of other embryo laboratories
accredited by the accreditation organization is reliably identifying
the deficiencies of the laboratories.
f. If the State determines that the accreditation organization has
not met the requirements of paragraph 2. of this section, the State may
(under such notice and hearing standards to be developed by the State)
revoke the approval of the accreditation program.
6. Revocation of an Accreditation Organization's State Approval. If
the State revokes approval of an accreditation organization under
subparagraph 5.f., of this section--
a. The State must notify each laboratory, accredited by the
organization under the State certification
b. The certification of any embryo laboratory accredited by the
organization will continue in effect for 60 days after the laboratory
is notified by the State of the withdrawal of approval, except that the
State may extend the period during which the certification may remain
in effect if the State determines that the laboratory submitted an
application to another approved accreditation organization for
accreditation or to the State, as applicable, in a timely manner after
receipt of such notice.
7. Embryo Laboratory Certification Revocation and Suspension.
a. A certification issued by a State for an embryo laboratory must
be revoked or suspended if the State or, as applicable, approved
accreditation organization finds, on the basis of inspections and after
reasonable notice and opportunity for hearing (under such notice and
hearing standards to be developed by the State) to the owner or
operator of the laboratory, that the owner or operator or any employee
of the laboratory--
i. Has been guilty of misrepresentation in obtaining the
certification.
ii. Has failed to comply with any standards of the certification
program.
iii. Has refused a request of the State or approved accreditation
organization for permission to inspect the laboratory, its operations,
and records.
b. If the certification of an embryo laboratory is revoked or
suspended, the certification of the laboratory shall continue in effect
for 60 days after the laboratory receives notice of the revocation or
suspension, unless there is a finding that the laboratory's continued
operation may constitute a public health threat, in which case the
certification shall be immediately revoked or suspended.
c. If the certification of an embryo laboratory is revoked or
suspended, the laboratory may apply for recertification after one year
after the date of the revocation or suspension.
8. Fees. The State may require the payment of fees for the purpose
of, and in an amount sufficient to cover the costs of, administering
the certification program.
Part III. Embryo Laboratory Standards
A. Personnel Qualifications and Responsibilities
The embryo laboratory must have a sufficient number of individuals,
who meet the qualification requirements, to perform the functions
necessary to provide timely services appropriate for the size and
volume of the assisted reproductive technology program(s) or clinic(s)
served by the laboratory. As a guideline, for every 90-150 assisted
reproductive technology cycles performed annually, the laboratory
should employ one individual who is capable of performing all assisted
reproductive technology laboratory procedures provided by the embryo
laboratory. Regardless of workload, at a minimum, two qualified
individuals should be available to provide the appropriate laboratory
services.
1. Laboratory Director Qualifications. The laboratory director must
be qualified to manage and direct the laboratory personnel and the
performance of assisted reproductive technology laboratory procedures.
The laboratory director must--
a. Possess a current license as an embryo laboratory director
issued by the State in which the laboratory is located, if such
licensing is required.
b. Be a physician or a doctoral scientist with a broad knowledge of
the biochemistry, biology, and physiology of reproduction, and
laboratory operations including experimental design, statistics, and
problem solving and meet the following.
i. Have two years documented pertinent experience in a laboratory
[[Page 60184]]
performing assisted reproductive technology procedures. This experience
should induce familiarity with laboratory quality control, sterile
technique and cell culture; and
ii. Have documented training of at least 1,000 hours in an embryo
laboratory which includes performing, at a minimum, each laboratory
component of the human assisted reproductive technology cycle 60 times.
Note: Documented experience and training may be acquired
concurrently.
c. If not qualified under paragraph 1.b. of this section, be the
director of an embryo laboratory on or before [date of publication of
final notice] and meet the following:
i. Have two years documented pertinent experience in a laboratory
performing assisted reproductive technology procedures. This experience
should induce familiarity with laboratory quality control, sterile
technique and cell culture; and
ii. Have documented training of at least 1,000 hours in an embryo
laboratory which includes performing, at a minimum, each laboratory
component of the human assisted reproductive technology cycle 60 times.
Note: Documented experience and training may be acquired
concurrently.
d. In addition to meeting the qualification requirements above,
obtain at least 12 contact hours of continuing education annually in
assisted reproductive technology or clinical laboratory practice.
2. Laboratory Director Responsibilities. The laboratory director is
responsible for the overall operation, administration, and technical
and scientific oversight of the embryo laboratory, including the
employment of personnel who are qualified to perform assisted
reproductive technology laboratory procedures, and record and report
procedural outcomes promptly, accurately and proficiently. If the
laboratory director delegates performance of his or her
responsibilities, he or she must do so in writing. The laboratory
director remains responsible for ensuring that all delegated duties are
properly performed. The laboratory director must--
a. Be accessible to the laboratory to provide onsite, telephone or
electronic consultations as needed.
b. Ensure that the physical plant (space, facilities and equipment)
and environmental conditions of the laboratory are appropriate for the
laboratory procedures performed and provide a safe environment in which
employees and other occupants are protected from physical, chemical,
electrical and biological hazards.
c. Establish and monitor a program to ensure that aseptic
conditions are maintained in the laboratory, as appropriate, for the
assisted reproductive laboratory procedures to be performed.
d. Ensure that assisted reproductive technology laboratory
procedures selected or developed by the laboratory are appropriate to
provide quality patient care.
e. Ensure that adequate systems are in place to maintain patient
confidentiality throughout those parts of the assisted reproductive
technology process under the laboratory's control.
f. Ensure that an approved procedure manual is available to all
personnel responsible for performing assisted reproductive technology
laboratory procedures.
g. Establish and monitor a quality management program to assure the
quality of laboratory services provided and to identify failures in
quality as they occur.
h. Ensure that all necessary corrective actions are taken,
documented and reviewed for effectiveness whenever failures in quality
are identified.
i. Provide consultation to physicians and others, as appropriate,
regarding the clinical significance of laboratory findings.
j. Employ a sufficient number of qualified personnel with the
appropriate education and documented experience or training to
supervise and perform the work of the laboratory. Written records of
the qualifications of all personnel must be maintained.
k. Ensure that all personnel receive appropriate training for the
assisted reproductive technology laboratory procedures to be performed,
and have demonstrated that they can perform the procedures reliably
prior to working on patients' specimens. All training activities must
be documented.
l. Ensure that all personnel acquire, on an annual basis, the
required number of continuing education contact hours. A record of each
employee's continuing education participation must be maintained.
m. Specify, in writing, the responsibilities and duties of each
person who performs assisted reproductive technology laboratory
procedures, identifying which procedures each individual is authorized
to perform and whether supervision is required.
n. Ensure that policies and procedures are established for
monitoring each employee's continued competence to perform assisted
reproductive technology laboratory procedures, and whenever necessary,
provide remedial training or additional continuing education to improve
skills.
o. Ensure that performance evaluations for each employee are
performed and documented, at a minimum, annually.
3. Laboratory Supervisor Qualifications. The embryo laboratory must
have one or more qualified supervisors who, under the direction of the
laboratory director, provide day-to-day supervision of laboratory
personnel performing assisted reproductive technology laboratory
procedures. In the absence of the director, the laboratory supervisor
must be responsible for the proper performance of all assisted
reproductive technology laboratory procedures. The laboratory
supervisor must--
a. Possess a current license issued by the State in which the
laboratory is located, if such licensing is required.
b. Meet the qualification requirements for an embryo laboratory
director under paragraph 1. of this section, or meet the following:
i. Have an earned master's or bachelor's degree in a chemical,
physical, biological, clinical laboratory or medical technology science
from an accredited institution; and
ii. Have documented training which includes performing, at a
minimum, each laboratory component of the human assisted reproductive
technology cycle 60 times.
c. If not qualified under subparagraph 3.b. of this section, be the
supervisor of an embryo laboratory on or before [date of publication of
final notice] and have documented training which includes performing,
at a minimum, each laboratory component of the human assisted
reproductive technology cycled 60 times.
d. In addition to meeting the qualification requirements above,
obtain at least 12 contact hours of continuing education annually in
assisted reproductive technology or clinical laboratory practice. If
also serving as the laboratory director, continuing education obtained
to meet the laboratory director qualification requirements may be used
to meet this requirement.
4. Laboratory Supervisor Responsibilities. The laboratory
supervisor is responsible for day-to-day supervision or oversight of
the embryo laboratory operation and personnel performing assisted
reproductive technology laboratory procedures. The laboratory
supervisor must--
a. Be accessible to laboratory personnel at all times when assisted
[[Page 60185]]
reproductive technology laboratory procedures are performed to provide
on-site, telephone or electronic consultation to resolve technical
problems in accordance with policies and procedures established by the
laboratory director.
b. Provide day-to-day supervision of laboratory personnel
performing assisted reproductive technology laboratory procedures.
c. Ensure direct and constant supervision of personnel undergoing
training in assisted reproductive technology laboratory procedures to
fulfill the qualification requirements for a reproductive biologist.
d. Perform laboratory director responsibilities as authorized in
writing by the laboratory director.
5. Reproductive Biologist Qualifications. Each individual
performing assisted reproductive technology laboratory procedures
must--
a. Possess a current license issued by the State in which the
laboratory is located, if such licensing is required.
b. Meet the qualification requirements for an embryo laboratory
director under paragraph 1. of this section, laboratory supervisor
requirements under paragraph 3. of this section, or meet the following:
i. Have an earned bachelor's degree in a chemical, physical,
biological, clinical laboratory or medical technology science from an
accredited institution; and
ii. Have documentation of training appropriate for the assisted
reproductive technology laboratory procedure(s) to be performed before
performing the procedure(s) without direct and constant supervision on
patient specimens. Training must include performing the assisted
reproductive technology laboratory procedure(s), at a minimum, 30 times
under direct and constant supervision.
c. If not qualified under subparagraph 5.b. of this section, be
performing assisted reproductive technology laboratory procedures in an
embryo laboratory on or before [date of publication of final notice]
and have documentation of training appropriate for the assisted
reproductive technology laboratory procedure(s) to be performed before
performing the procedure(s) without direct and constant supervision on
patient specimens. Training must include performing the assisted
reproductive technology laboratory procedure(s), at a minimum, 30 times
under direct and constant supervision.
d. In addition to meeting the qualification requirements above,
obtain at least 12 contact hours of continuing education annually in
assisted reproductive technology or clinical laboratory practice. If
also serving as the laboratory director or laboratory supervisor,
continuing education obtained to meet the laboratory director or
laboratory supervisor qualification requirements may be used to meet
this requirement.
6. Reproductive Biologist Responsibilities. The reproductive
biologist is responsible for performing assisted reproductive
technology laboratory procedures, and recording and reporting
procedural outcomes promptly, accurately and proficiently. The
reproductive biologist must--
1. Perform only those assisted reproductive technology laboratory
procedures that are authorized by the laboratory director, and for
which training has been documented. If appropriate training has not
been documented, perform assisted reproductive technology laboratory
procedures only under direct and constant supervision.
b. Follow the laboratory's established policies and procedures for
performing assisted reproductive technology laboratory procedures, and
recording and reporting procedural outcomes.
c. Adhere to the laboratory's quality management policies, document
all specimen and procedure management, quality control and quality
assurance activities, and equipment and instrument calibration,
function verification and maintenance performed.
d. Identify problems that may adversely affect the performance of
assisted reproductive technology laboratory procedures and either
immediately notify the laboratory supervisor or director, or correct
the problem(s) in accordance with the laboratory's established policies
and procedures and notify the laboratory supervisor or director of the
problem(s) and the corrective action(s) taken.
e. Document all corrective actions taken when failures in quality
are identified.
B. Facilities and Safety
The embryo laboratory must provide adequate space and the
appropriate environmental conditions to ensure safe working conditions
and quality performance of assisted reproductive technology laboratory
procedures.
1. Requirements for Physical Space and Utilities. The laboratory
must be constructed and arranged so that--
a. The laboratory space, ventilation, and utilities are adequate
for the volume of assisted reproductive technology laboratory
procedures performed during peak periods of activity.
b. Assisted reproductive technology laboratory procedures are
carried out in a secure area with access limited to authorized
personnel.
c. Movement of patient specimens and traffic around sensitive work
areas is limited in order to reduce the potential for spilled or lost
specimens.
d. Incubator and storage space are configured to ensure positive
specimen identification and minimize the potential for errors due to
misplaced specimens or retrieval of the wrong specimen.
e. Activities requiring sterile technique such as the handling,
assessment and culturing of human oocytes and embryos, are performed
under aseptic conditions in an area that is physically isolated from
other laboratory activities.
f. All laboratory work areas (does not include administrative
areas) are easily washed and disinfected.
g. The laboratory and administrative space are conveniently
located, but are separate from patient areas.
h. Immediate communication can occur with the oocyte retrieval and
transfer room(s).
2. Safety Requirements. Safety precautions, policies, and
procedures must be established and posted, or readily available to all
personnel, to ensure protection from physical, chemical, electrical and
biological hazards.
a. All personnel must be knowledgeable about and abide by
applicable Federal, State and local regulations regarding protection
from physical, chemical, electrical and biological hazards.
b. Disposable materials should be used wherever possible for all
procedures that involve exposure to tissue and body fluids.
c. The laboratory must store and dispose of tissue, body fluids, or
other potentially biohazardous materials as outlined in Federal, State
and local regulations.
d. Toxic chemicals, including toxic cleaning materials, must be
used in a manner that is not harmful to patient specimens.
e. Radioisotopes must not be used in a laboratory that performs
assisted reproductive technology procedures.
f. The laboratory must have an emergency plan appropriate for its
geographical location which specifies the actions to be taken to
protect employees, patients, visitors and specimens in case of a
natural disaster or other potentially devastating event.
[[Page 60186]]
3. Laboratory Animals. If laboratory animals are used, all
applicable Federal, State and local regulations regarding animal care
and use must be met. Animal specimens must be--
a. Handled and stored separately from human specimens.
b. Incubated separately from human specimens, unless program/
institutional approval is given for an application involving specific
cell lines, i.e., animal coculture.
C. Quality Management
The embryo laboratory must establish and follow written policies
and procedures for a comprehensive quality management program that is
designed to monitor and evaluate the ongoing and overall quality of the
assisted reproductive technology laboratory procedures performed and
services provided. All quality management activities must be
documented.
1. Procedure Manual. A written procedure manual including
instructions for all assisted reproductive technology laboratory
procedures performed must be available in the embryo laboratory and
followed by all laboratory personnel. The written procedures must be in
sufficient detail to assure reproducibility and competence in the
performance of the laboratory procedures.
a. The procedure manual include the following, when applicable to
the assisted reproductive technology laboratory procedure performed:
i. Principle (scientific basis) of the assisted reproductive
technology laboratory procedure;
ii. Clinical significance of the assisted reproductive technology
laboratory procedure;
iii. Requirements for specimen collection and handling;
iv. Step-by-step instructions for performance of the assisted
reproductive technology laboratory procedure;
v. Preparation of required reagents, culture media, solutions, or
other special supplies;
vi. Equipment and instrumentation required for the performance of
the procedure, including necessary function checks and calibration
protocols;
vii. Quality control procedures to be performed, including
frequency of control testing, and criteria for acceptability;
viii. Remedial action to be taken when function checks, calibration
or control results do not meet the laboratory's criteria for
acceptability;
ix. Calculations and interpretation of procedural outcomes,
including criteria for acceptable and unacceptable outcomes, and
procedural outcomes requiring special notification;
x. The laboratory's system for recording and reporting procedural
outcomes;
xi. Limitations in methodologies, including interfering substances
and precautions;
xii. Pertinent literature references;
xiii. Description of the course of action to be taken if required
equipment or instrumentation malfunctions or is inoperable;
xiv. Criteria for the referral or transfer of specimens to another
embryo laboratory for the performance of an assisted reproductive
technology laboratory procedure, including procedures for specimen
submission and handling; and
xv. Procedure for safe and appropriate specimen disposal.
b. Manufacturers' instrument/equipment manuals and package inserts
may be used, when applicable, to meet the requirements of this section.
i. Any of the items listed under subparagraph 1.a. of this section,
not provided by the manufacturer must be provided by the laboratory.
ii. Any modifications to, or deviations from, the manufacturer's
instructions, must be clearly documented and provided in the procedure
manual.
c. Appropriate reference materials (e.g., slides, pictures,
textbooks, etc.) should be available in the laboratory to allow, as
needed, comparison with patient specimens.
d. Procedures must initially be approved, signed and dated by the
laboratory director, and must thereafter, be reviewed by the laboratory
director on an annual basis.
e. Procedures must be re-approved, signed and dated if the
directorship of the laboratory changes.
f. Each change in a procedure must be approved, signed and dated by
the current laboratory director.
g. The laboratory must retain a copy of each procedure with the
dates of initial use and discontinuance in accordance with the
requirements of section D., Maintenance of Records, of this part.
2. Equipment and Instrument Maintenance/Calibration. The embryo
laboratory must perform and document equipment and instrument
maintenance and, as applicable, calibration, and function verification
that include(s) electronic, mechanical and operational checks necessary
for the proper performance of assisted reproductive technology
laboratory procedures. The laboratory must--
a. Have sufficient equipment for the type and volume of assisted
reproductive technology laboratory procedures performed, which may
include but is not limited to, incubators, freezers, refrigerators,
hoods, thermometers, centrifuges, microscopes, pipettes, and warming
devices.
b. Establish and follow written policies and procedures for
equipment and instrument maintenance and, as applicable, calibration,
and function checks, that ensure proper performance of the equipment
and instruments used in assisted reproductive technology laboratory
procedures.
The laboratory must--
i. Define acceptable limits for equipment and instrument
maintenance and, as applicable, calibration, and function checks prior
to their use in assisted reproductive technology laboratory procedures.
ii. Perform maintenance and, as applicable, calibration, and
function checks in accordance with the equipment/instrument
manufacturer's instructions and at the frequency required to ensure
adequate performance of the equipment and instruments used in assisted
reproductive technology laboratory procedures.
iii. Monitor environmental conditions, using an independent
measuring device, in critical equipment, including but not limited to,
incubators, controlled-rate freezers and liquid nitrogen storage tanks,
at a frequency that ensures timely detection of conditions that are
deleterious to specimens. These conditions include, if applicable:
A. Temperature;
B. Humidity;
C. Gas concentration; and
D. Liquid nitrogen levels.
iv. Maintain an alarm system on critical equipment that will
immediately detect when pre-established limits for the environmental
conditions listed in subparagraph 2.b.iii. (excluding humidity), of
this section, are exceeded. The alarm system must be:
A. Checked periodically to ensure that it will be triggered when
preestablished limits for environmental conditions are exceeded; and
B. Monitored 24 hours a day in the laboratory or at a remote site.
v. Protect critical equipment and instrumentation from fluctuations
and interruptions in electrical current.
vi. Have available emergency back-up capability for critical
equipment, including but not limited to, incubators, refrigerators and
controlled-rate freezers.
vii. Document all maintenance, calibration, and function checks
performed.
[[Page 60187]]
c. Identify, investigate, and correct problems with equipment or
instrumentation that may adversely affect the performance of assisted
reproductive technology laboratory procedures.
d. Document all corrective actions taken when problems with
equipment or instrumentation are identified.
3. Labeling, Handling, and Storage of Chemicals, Reagents,
Solutions, Culture Media, Materials and Supplies. The embryo laboratory
must label, handle and store chemicals, reagents, solutions, culture
media, materials and supplies in a manner that ensures their positive
identification, optimum integrity and appropriate reactivity in
assisted reproductive technology laboratory procedures. The laboratory
must--
a. Have a mechanism for ensuring sufficient chemicals, reagents,
solutions, culture media, materials and supplies for the type and
volume of assisted reproductive technology laboratory procedures
performed (e.g., inventory maintenance program).
b. Define criteria that are essential for proper storage of
chemicals, reagents, solutions, and culture media, including the
following, as applicable:
i. Temperature;
ii. Humidity; and
iii. Other conditions necessary for proper storage.
c. Label all chemical, reagents, solutions, and culture media to
indicate the following, as applicable:
i. Identity, and when significant, batch or lot number, titer,
strength, or concentration;
ii. Recommended storage conditions;
iii. Expiration date; and
iv. Other pertinent information required for proper use.
d. Verify that materials which come in contact with sperm, oocytes,
and embryos have been tested and found to be non-toxic to sperm,
oocytes, and embryos. Documentation supplied by the manufacturer may be
used to meet this requirement.
e. Maintain records documenting the batch or lot number, date of
receipt or preparation, and date placed in use, for all chemicals,
reagents, solutions, and culture media.
f. Prepare, store, and handle chemicals, reagents, solutions, and
culture media in a manner to ensure that they are not used when they
have exceeded their expiration date, have deteriorated, or are of
substandard quality.
4. Specimen and Procedure Management. The embryo laboratory must
have written protocols and criteria for the laboratory procedures
performed and employ and maintain a system that provides for proper
patient identification and preparation; specimen collection,
identification, and handling (transportation, processing, storage,
preservation); and accurate recording and reporting of laboratory
procedural outcomes.
a. The laboratory must have available and follow written policies
and procedures for each of the following:
i. Instructions for patient preparation, if applicable;
ii. Methods used for the positive identification of patients;
iii. Specimen collection;
iv. The labeling of patient specimens to ensure positive
identification from the time of specimen collection through final
disposition or disposal;
v. Criteria for maintaining specimen integrity and viability during
transport, storage and the performance of assisted reproductive
technology laboratory procedures including, as applicable, requirements
for:
A. Temperature;
B. Humidity; and
C. Gas concentration; and
vi. Criteria for specimen acceptability and, as appropriate,
instructions for special handling of suboptimal specimens.
b. The laboratory must have adequate systems in place to ensure
patient confidentiality throughout those parts of the assisted
reproductive technology process that are under the laboratory's
control.
c. The laboratory may perform assisted reproductive technology
laboratory procedures only at the written or electronic request of an
authorized person. Oral requests for changes to the original written or
electronic request must be documented by the laboratory and followed by
receipt of written or electronic documentation from an authorized
person within 24 hours of the oral request. The patient's chart or
medical record may be used for written authorization, but must be
available to the laboratory at the time of the laboratory procedure.
Written or electronic authorization must include the following:
i. The patient's name and unique identifier;
ii. When applicable, the partner's or donor's name or other unique
identifier;
iii. The name and address or other suitable identifiers of the
authorized person requesting the procedure, and the name of the
individual communicating the request;
iv. The procedure(s) to be performed;
v. The date(s) and time(s) the procedures(s) is to be performed;
and
vi. Any additional information relevant and necessary to the
performance of the procedure(s) including verification of informed
patient consent, and as applicable, special handling instructions and
any instructions stipulated by the patient.
d. As applicable, the laboratory must establish and follow written
protocols, including documented criteria, for--
i. Evaluation and assessment of oocyte morphology and maturity,
fertilization, and embryo quality.
ii. Insemination schedule relative to oocyte maturity.
iii. Volume, numbers, and quality of sperm used for insemination of
each oocyte.
iv. Disposition of oocytes with an abnormal number of pronuclei.
v. Disposition of excess oocytes.
vi. The time period following insemination for examination of
oocytes to determine fertilization.
vii. Micromanipulation of oocytes and embryos.
viii. Re-insemination of oocytes.
ix. Cryopreservation of specimens.
x. Embryo transfer procedures, which include the following:
A. The length of time embryos are cultured prior to transfer;
B. The medium and protein supplementation used for transfer, as
applicable;
C. Disposition of excess embryos;
D. Types of catheters available, with circumstances for use of
each;
E. Method of transfer; and
F. Technique for post transfer catheter check.
e. The laboratory must maintain a record system, for each patient's
assisted reproductive technology cycle, to ensure reliable
identification and control of the patient's specimens as they are
received and the laboratory procedure(s) performed. The record system
must include documentation of the information specified in subparagraph
4.c. of this section, and--
i. The laboratory accession number, or other unique identification
of the specimen.
ii. The date and time of specimen receipt into the laboratory and,
as applicable, the number of oocytes retrieved and assessment of each
oocyte or cumulus corona complex.
iii. The condition and disposition of all specimens including those
that do not meet the laboratory's criteria for acceptability.
iv. The records and dates of all laboratory handling and
procedures, including the following, as applicable:
A. Semen assessment before and after washing and concentration for
insemination;
B. Outcome of insemination or micromanipulation procedures (e.g.,
fertilization);
[[Page 60188]]
C. Outcome of any culture (e.g., cleavage);
D. Relative timing of protocol events (incubation hours, etc.);
E. Assessment of the developmental status and quality of all
embryos at transfer;
F. Verification that no embryos remain in the catheter following
completion of transfer;
G. The identity and lot numbers of the media and media supplements
used in each phase of the procedure; and
H. The identity of the laboratory personnel who handled the
specimens and performed the procedures.
f. The laboratory must have a mechanism in place for promptly
providing the authorized person who ordered the procedure a complete
summary of all procedural outcomes and the occurrence of any unusual or
abnormal events, including the condition and disposition of specimens
that do not meet the laboratory's criteria for acceptability.
g. The laboratory must have an accurate and reliable method of
tracking cryopreserved specimens ensuring positive identification of
each cryopreservation container. In addition, the cryopreservation
container must be labeled with the patient's name or unique identifier,
and the date the specimen(s) was frozen. All labeling must be of a
permanent nature. Documentation must be maintained in duplicate log
books or files for each liquid nitrogen storage tank and include the
following:
i. The patient's name or other unique identifier;
ii. A description of each cryopreservation container's contents;
iii. The freezing protocol used;
iv. Date frozen;
v. Type and location of cryopreservation container (e.g., straw,
vial); and
vi. Final disposition/disposal of the cryopreserved specimen(s).
h. If cryopreserved specimens are received from or transferred to
other facilities, the laboratory must have written policies and
procedures for the receipt/transfer of cryopreserved specimens.
Policies and procedures must include appropriate methods of
transportation and the method for verifying the identification and
number of cryopreservation containers received/transferred. In
addition, documentation of the freezing protocol used, and copies of
patient release forms and applicable log sheets must accompany the
cryopreserved specimens.
i. Clinical laboratory testing on specimens obtained by the embryo
laboratory must be performed in accordance with the regulations
implementing CLIA at 42 CFR Part 493. In addition--
i. The referring embryo laboratory must not revise results or
information directly related to the interpretation of results provided
by the testing laboratory.
ii. The referring embryo laboratory may permit the testing
laboratory to send the test result(s) directly to the authorized person
who initially requested the testing. The embryo laboratory must retain
or be able to produce an exact duplicate of the testing laboratory
report.
iii. The authorized person who orders a clinical laboratory test
must be notified by the referring embryo laboratory of the name and
address of the testing laboratory.
5. Method Validation. All assisted reproductive technology
procedures selected or established by the embryo laboratory must be
validated by the laboratory prior to routine patient use. The
laboratory must determine appropriate performance measures and
demonstrate that the procedure, when performed by the laboratory's
staff, meets or exceeds acceptable levels of performance as defined by
the laboratory. In addition, the laboratory must periodically verify,
through its quality management activities (as specified in this part),
each procedure's continued acceptable level of performance. All
validations must be documented.
6. Quality Control. The embryo laboratory must establish and follow
written quality control procedures at a frequency appropriate to
monitor the reliability of the assisted reproductive technology
laboratory procedures performed. All quality control activities must be
documented. The laboratory must--
a. Establish acceptability criteria for all quality control
procedures.
b. Perform and document the remedial action(s) taken when problems
are identified or quality control procedures do not meet the
laboratory's criteria for acceptability.
c. For each laboratory procedure performed and, as applicable,
culture media preparation--
i. Define and use the appropriate grade of water required.
ii. Periodically monitor water quality to ensure that its quality
continues to meet the laboratory's specifications for its intended use.
As applicable, adherence to manufacturers' storage and handling
requirements, and expiration dates may meet this requirement.
d. As applicable, have and follow a written procedure for the
preparation, washing and sterilization of glassware used in the
laboratory's procedures that includes the following:
i. Rinsing all washable glassware with distilled or deionized water
prior to drying; and
ii. If detergent is used, testing washed items for detergent
removal.
e. Have and follow a written procedure for the quality control of
culture media which includes a visual check for physical damage to the
media container and evidence of media contamination prior to its use
and--
i. For each batch of culture media prepared in-house, document the
quality of the media by testing--
A. pH.
B. Osmolality.
C. Culture suitability using an appropriate bioassay system.
ii. For each batch of commercially prepared culture media--
A. Verify and document the quality of the media with an appropriate
bioassay system. Documentation of quality control performed by the
manufacturer may meet this requirement.
B. Follow the manufacturer's specifications for using the media.
iii. Test and document the quality of any media supplementation
(e.g., protein), when appropriate, using a bioassay system.
iv. Test blood based media supplements (e.g., human fetal cord
serum) prepared in-house with a FDA licensed, approved, or cleared test
and show the supplement to be negative/nonreactive for the following
communicable diseases prior to use:
A. Human immunodeficiency virus, Type 1 (e.g., anti-HIV-1);
B. Human immunodeficiency virus, Type 2 (e.g., anti-HIV-2);
C. Hepatitis B virus (e.g., HbsAg);
D. Hepatitis C virus (e.g., anti-HCV);
E. Human T-cell lymphotrophic virus, Type I (e.g., anti-HTLV-I);
and
F. Such other diseases that may be later added to this list.
Note: A batch of media (solid, semi-solid, or liquid) consists
of all tubes, plates, or containers of the same medium prepared at
the same time in the laboratory; or, if received from an outside
source of commercial supplier, consists of all of the plates, tubes
or containers of the same medium that have the same lot numbers and
are received in a single shipment.
7. Quality Assurance. The embryo laboratory must establish and
follow written policies and procedures for a quality assurance program
to monitor the quality of services provided by the laboratory, and
resolve problems that are identified. The laboratory must have a
mechanism to evaluate the effectiveness of its policies and
[[Page 60189]]
procedures; identify and correct problems; and assure the adequacy and
competency of the staff. As necessary, the laboratory must revise its
policies and procedures based on the results of those evaluations. All
quality assurance activities must be documented.
a. The laboratory must have an ongoing mechanism for monitoring,
evaluating and revising, if necessary, based on the results of its
evaluations, the following:
i. The criteria established for patient identification and specimen
collection, identification, and handling;
ii. The information requested and maintained on each patient and
for each laboratory procedure performed for its completeness, relevance
and necessity;
iii. The timeliness and accuracy of recording and reporting
procedural outcomes;
iv. The accuracy and reliability of tracking cryopreserved
specimens;
v. The appropriate storage and retrieval of laboratory records such
as procedural outcomes, and other data recorded and maintained; and
vi. The corrective actions taken for--
A. Problems identified during the evaluation of equipment and
instrument maintenance, calibration, and function check data.
B. Problems identified during the evaluation of quality control
data.
C. Errors detected in patient or specimen identification and
handling.
D. Clerical or analytical errors detected in laboratory records.
b. The embryo laboratory must have an ongoing mechanism to--
i. Identify and evaluate laboratory procedural outcomes that appear
inconsistent with the patient or donor history.
ii. Track and evaluate laboratory procedural outcomes including,
but not limited to, fertilization rates, cleavage rates and embryo
quality.
iii. Maintain a file of adverse reactions occurring as a result of
errors made during the performance of assisted reproductive technology
laboratory procedures.
iv. Evaluate the effectiveness of its policies and procedures for
assuring employee competence in performing assisted reproductive
technology laboratory procedures.
v. Document problems that occur as a result of a breakdown in
communication between the laboratory and referring physicians or others
involved in the assisted reproductive technology procedures, and take
corrective actions to resolve the problems and minimize future
communications breakdowns.
vi. Assure that all complaints and problems reported to the
laboratory are documented. Investigations of complaints must be made,
when appropriate, and as necessary, corrective actions must be
instituted.
vii. Document and assess problems identified during quality
assurance reviews, and discuss them with the laboratory staff and, as
appropriate, referring physicians and others involved in the assisted
reproductive technology procedures. The laboratory must take the
necessary corrective actions to prevent recurrences.
D. Maintenance of Records
The embryo laboratory must retain records of all of its policies
and procedures; personnel employment, training, evaluations and
continuing education activities; and quality management activities
specified in this part.
1. Record Format. Laboratory records must be accurate, indelible,
and legible. Records may be retained electronically, or as original
paper records, or as true copies such as photocopies, microfiche, or
microfilm.
2. Retention Period. Laboratory records must be retained in
accordance with time frames specified by applicable Federal, State and
local laws or for ten years beyond the date of final disposition or
disposal of all specimens obtained during each patient's assisted
reproductive technology cycle, whichever is later. Records must be
retained on site for two years. Note: Transfer of cryopreserved
specimens to another facility constitutes final disposition for the
transferring facility.
3. Record Retrieval. Laboratory records must be maintained in a
manner which ensures timely, accurate and reliable retrieval.
4. Laboratory Closure. In the event that the laboratory ceases
operation, the laboratory must make provisions for these records to be
maintained for the time frame required above.
Addendum
References
1. The American Association of Bioanalysts. Embryology and
Andrology Review Course. American Association of Bioanalysts, St.
Louis, Missouri, 1994.
2. The American Association of Tissue Banks. Standards for Tissue
Banking. The American Association of Tissue Banks, McLean, Virginia,
1996.
3. The American Fertility Society. Guidelines for Human Embryology
and Andrology Laboratories. Fertility and Sterility 1992;58(Suppl 1)
:1S-16S.
4. Association of Clinical Embryologists. Accreditation Standards
and Guidelines for IVF Laboratories. Association of Clinical
Embryologists, London, England, 1996.
5. California Health and Safety Code, Division 2, Chapter 4.1--
Tissue Banks. State of California, Department of Health Services,
Berkeley, California, 1992.
6. Centers for Disease Control and Prevention. Reporting of
Pregnancy Success Rates from Assisted Reproductive Technology Programs.
62 FR 45259, Aug. 26, 1997.
7. Code of Federal Regulations, Title 42, Chapter IV, Part 493--
Laboratory Requirements.
8. The College of American Pathologists/American Society for
Reproductive Medicine Reproductive Laboratory Accreditation Program.
The College of American Pathologists, Northfield, Illinois, 1996.
9. The Fertility Clinic Success Rate and Certification Act of 1992
(Public Law 102-493).
10. Keel BA and BW Webster. CRC Handbook of the Laboratory
Diagnosis and Treatment of Infertility. CRC Press, Inc., Boca Raton,
Florida, 1990.
11. Rules and Regulations of the State of New York, Part 52 of
Title 10 (Health). Tissue Banks and Non-transplant Anatomic Banks.
State of New York Department of Health, Albany, New York, 1992.
12. Senate Report 102-452 on H.R. 4773. Fertility Clinic Success
Rate and Certification Act of 1992. 102d Congress, 2d Session, 1992.
13. Veeck LL. The Gamete Laboratory: Design, Management and
Techniques. pp. 798-820 in: Infertility: Evaluation and Treatment.
Edited by WR Keye, RJ Chang, RW Rebar and MR Soules. WB Saunders,
Philadelphia, Pennsylvania, 1995.
[FR Doc. 98-29374 Filed 11-5-98; 8:45 am]
BILLING CODE 4163-18-M
