[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]]

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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.

-----------------------------------------------------------------------

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