Implementation of the Fertility Clinic Success Rate and Certification Act of 1992; Proposed Model Program for the Certification of Embryo Laboratories

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

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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