Health Canada Directive: Technical Requirements for Therapeutic Donor
Insemination
Therapeutic Products Programme
OUR MISSION: To ensure that the drugs, medical devices, and other
therapeutic products available in Canada are safe, effective and of high
quality
July 2000
TABLE CONTENTS
PREFACE
A. LIST OF ABBREVIATIONS
B. DEFINITIONS
C. SEMEN DONOR RECRUITMENT, SCREENING AND TESTING
1. DONOR SELECTION - GENERAL
1.1 Recruitment
1.2 Donor Screening Procedures
1.3 Medical Records
2. EXCLUSIONS
2.1 Exclusion Criteria
2.2 Semen Processed Prior to March 14, 2000
3. WORK-UP
3.1 Suitability of Donor
3.2 Questionnaire
3.3 Donor Selection Process
3.3.1 Donor Information Sheet
3.3.2 Required Elements
3.4 Documentation
3.5 Initial Testing
3.5.1 General
3.5.1.1 Infectious Disease Testing
3.5.1.2 Notification Requirement
3.5.2 Minimum Serological Testing
3.5.3 Additional Serological Testing
3.5.4 Minimum Microbiological Testing
3.6 Rh Status
3.7 Archived Serum Samples
3.8 Semen Processed Prior to March 14, 2000
4. REPEAT SCREENING & QUARANTINE
4.1 Repeat Screening
4.1.1 Serological Testing
4.1.2 Cytomegalovirus (CMV) IgM & IgG.
4.1.3 Microbiological Testing
4.1.4 Physical Examination
4.2 Quarantine and Repeat Screening
4.2.1 Quarantine Period
4.2.2 Repeat Screening Prior to Distribution
4.3 Evaluation of Semen Safety
4.3.1 Role of the Medical Director or Physician Designated
by the Medical Director
4.3.2 Semen Release
4.4 Semen Processed Prior to March 14, 2000
5. MICROBIOLOGY
5.1 Chlamydia trachomatis and Neisseria gonorrhoeae
5.2 General Culture and Sensitivity Evaluation
5.3 Antibiotics
5.4 Semen Processed Prior to March 14, 2000
6. SEMEN PROCESSED PRIOR TO MARCH
14, 2000
6.1 Exclusion Criteria
6.2 Serological Testing
6.2.1 Work-Up
6.2.2 Repeat Screening and Quarantine
6.2.2.1 Fully Processed Semen
6.2.2.2 Partially Processed Semen
6.3 Microbiology
6.4 Other Measures
7. ADDITIONAL INFORMATION
PREFACE
The Health Canada Directive entitled Technical Requirements for Therapeutic
Donor Insemination is intended to minimize the risk of disease transmission
via donated semen. Clauses 2 to 5 of this Directive, entitled "Exclusions",
"Work-Up", "Repeat Screening & Quarantine" and
"Microbiology", specify the minimum requirements for screening
and testing donors of semen for use in assisted conception.
In this Directive, the words "shall" or "must" indicate
a requirement. The term "should" indicates a recommendation.
Notes accompanying clauses do not include mandatory or alternative requirements.
The purpose of these notes is to set out explanatory or informative material.
A. LIST OF ABBREVIATIONS
AIDS Acquired Immuno-Deficiency Syndrome
CJD Creutzfeldt-Jakob
Disease
CMV Cytomegalovirus
DI Donor
Insemination
FTA-ABS Fluorescent Treponemal Antibody Absorption Test
HBc Ag Hepatitis
B Core Antigen
HBs Ag Hepatitis
B Surface Antigen
HBV Hepatitis
B Virus
HCV Hepatitis
C Virus
HIV Human
Immunodeficiency Virus
HTLV Human
T-cell Lymphotropic Virus
IgG Immune
Globulin G
IgM Immune
Globulin M
MHA-TP
Microhemagglutination Assay for Treponema pallidum
SOPs Standard
Operating Procedures
TDI Therapeutic
Donor Insemination
B. DEFINITIONS
Canadian STD Guidelines: The 1998 Edition of the Canadian Sexually
Transmitted Disease (STD) Guidelines (ISBN- O-662-27208-0; website availability
at http://www.hc-sc.gc.ca/hpb/lcdc/bah), as amended from time to time.
CFAS 1996 Guidelines: The Canadian Fertility and Andrology Society
1996 Guidelines for Therapeutic Donor Insemination.
Note: The Guidelines for Therapeutic Donor Insemination,
as amended from time to time, published by the Canadian Fertility and
Andrology Society, Montreal, were referenced in the Processing and Distribution
of Semen for Assisted Conception Regulations, made under the Food and
Drugs Act.
Repeatedly Reactive: A blood sample which is reactive on initial
testing, and is still reactive in at least one of two duplicate samples
when the same test is repeated using the same blood sample.
Semen Fully Processed Prior to March 14, 2000: Semen in
respect of which the measures referred to under the following headings
have been taken prior to March 14, 2000:
- "Exclusions", "Work-Up", "Repeat Screening
& Quarantine" and "Semen Microbiology" of the CFAS
1996 Guidelines; or
- "Exclusions", "Work-Up", "Repeat Screening
& Quarantine" and "Microbiology" of this Directive.
C. SEMEN DONOR RECRUITMENT, SCREENING AND TESTING
1. DONOR SELECTION - GENERAL
1.1 Recruitment
Any healthy men not excluded on the basis of the criteria set out under
the heading "Exclusions" in Clause 2 are eligible to donate
semen.
1.2 Donor Screening Procedures
Each semen bank or fertility clinic shall adhere to donor screening procedures
as specified in the facility's Standard Operating Procedures (SOPs) and
this Directive.
1.3 Medical Records
Medical records regarding the donor should be kept indefinitely.
2. EXCLUSIONS
2.1 Exclusion Criteria
The exclusion criteria shall include the following:
- Employment by the facility or having a family member employed by
the facility;
- Age greater than 40 years;
- Indications of high risk for the Human Immunodeficiency Virus (HIV),
Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human T-cell Lymphotropic
Virus (HTLV), including:
- men who have had sex with another man, even once, since 1977;
- persons who report intravenous, intramuscular, or subcutaneous injection
of drugs that are not prescribed by a licensed physician for medical
purposes;
- persons who report tattoos or body piercing involving non-sterile
skin penetration in the preceding 12 months;
- persons with hemophilia or related clotting disorder who have received
human derived clotting factor concentrates;
- persons who have engaged in sex in exchange for money or drugs at
anytime since 1977;
- persons who have had sex in the preceding 12 months with any person
described in item (c)(i) through (c)(v) above;
- persons who have been exposed to known or suspected HIV infected
blood or body fluids through percutaneous inoculation or through contact
with an open wound, non-intact skin, or mucous membrane;
- persons who cannot be tested for infectious disease agents because
of refusal, inadequate blood sample, or other reasons;
- persons with a history of repeatedly reactive screening for antibody
to HIV-1 or HIV-2, Hepatitis B surface antigen (HBsAg), antibody to
Hepatitis B core (HBc) antigen, antibody to HCV, or antibody to HTLV-I
or HTLV-II, regardless of the results of supplemental assays;
- persons whose history, physical examination, medical records, or
pathology report reveal other evidence of infection or high-risk behaviours,
such as:
diagnosis with Acquired Immuno-Deficiency Syndrome (AIDS);
unexplained weight-loss;
night sweats;
blue or purple spots on the skin or mucous membranes typical of Kaposi's
Sarcoma;
unexplained lymphadenopathy lasting more than 1 month;
unexplained temperature greater than 38.6 oC (100.5 F) for more than
10 days;
unexplained persistent diarrhea; or
needle tracks or other signs of parenteral drug use;
- persons who have, or have had, sex with a person known to have HIV,
HBV, HCV, or HTLV infection, or who is at high risk for such infection;
- persons who are at risk of having acquired HIV from geographic regions
which are endemic for HIV strains that are not detectable by current
screening tests (these individuals may be reconsidered once tests to
detect the variant strains become available);
Note: Information regarding geographic regions which are endemic for
HIV strains that are not detectable by current screening tests is available
at Health Canada.
- persons with active viral hepatitis;
- persons who have received, or whose sexual partners have received
blood, blood components, blood products or other human tissues in the
preceding 12 months;
- persons who have been exposed to blood or body fluids through percutaneous
inoculation or through contact with an open wound, non-intact skin,
or mucous membrane in the preceding 12 months;
- persons who have been excluded permanently from donating blood;
- persons who have used intra-nasal cocaine in the preceding 12 months;
Note: The criteria outlined in clause 2.1(c) have been excerpted
from the Guidelines for Preventing Transmission of Human Immunodeficiency
Virus Through Transplantation of Human Tissues and Organs - Morbidity
and Mortality Weekly Report (MMWR), U.S. Center for Disease Control: 43;
RR8, May 29, 1994, and modified to conform with the exclusion criteria
for Canadian blood donors.
- Sexually transmitted disease in the preceding 12 months;
- Sexual encounter in the preceding 12 months with someone whose sexual
background the potential donor is unsure of;
- Urethral discharge, genital warts, or genital ulcers at the time
of donation;
- History of alcoholism;
- Diagnosis with Creutzfeldt-Jakob Disease (CJD) or a first degree
family member with a history of CJD;
- Receipt of human pituitary-derived growth hormone or dura mater;
- Spongiform encephalopathy or prion disease;
- Viral encephalitis or encephalitis of unknown origin; or
- Any major systemic diseases, including systemic malignancies.
2.2 Semen Processed Prior to March 14, 2000
For semen processed prior to March 14, 2000, only the measures set out
in Clause 6 apply.
3. WORK-UP
3.1 Suitability of Donor
The suitability of a specific individual for semen donation shall be
documented and based on medical, sexual and social history, clinical status,
physical examination, and laboratory test results.
3.2 Questionnaire
The Medical Director or a Physician Designated by the Medical Director
shall be responsible for the preparation of medical, social and sexual
history questionnaires.
3.3 Donor Selection Process
3.3.1 Donor Information Sheet
A donor information sheet should be provided to the donor.
3.3.2 Required Elements
- The donor selection process shall include the following:
- i. staff designated by the Medical Director of the semen bank
or fertility clinic shall have initial discussions with the potential
donor. The discussion shall emphasize the importance of the Donor
Insemination (DI) Programmes and the donors' responsibilities towards
them;
- a donor consent form shall be completed by the donor; and
- a donor medical questionnaire must be completed.
- A preliminary semen evaluation, including a cryopreservation test,
shall be conducted.
- A medical interview shall be conducted, and shall include:
- a physical examination;
- a medical history; and
- laboratory tests, including the infectious disease tests specified
in Clauses 3.5.2 and 3.5.4. The infectious disease tests specified
in Clause 3.5.3 should also be performed.
- The acceptance of a donor shall be decided by the Medical Director
or a Physician Designated by the Medical Director.
- If a donor is accepted, a unique identifier shall be assigned to
that donor. The semen bank or fertility clinic shall be responsible
for ensuring donor confidentiality.
3.4 Documentation
Documentation in respect of each donor shall include the following:
- Name of the donor;
- Unique identifier of the donor;
- Address of the donor;
- Donor's date of birth;
- Completed medical questionnaire;
- Completed donor consent form;
- Medical records;
- Completed physical examination results;
- Laboratory test results; and
- Name and signature of the Medical Director or a Physician Designated
by the Medical Director, who reviewed, examined and approved the semen
donor.
3.5 Initial Testing
3.5.1 General
3.5.1.1 Infectious Disease Testing
- The Standard Operating Procedures (SOPs) of every semen bank or fertility
clinic shall describe all infectious disease tests that must be performed.
- Testing shall be performed by a laboratory that meets federal accreditation
requirements, or the accreditation requirements of the province or territory
in which the laboratory is located, or in the case of imported semen,
by a laboratory that meets a recognized equivalent accreditation requirement.
- The serological tests specified in Clause 3.5.2 shall be performed
on a blood specimen obtained from the semen donor:
- with donor screening test kits approved or licensed under the
Canadian Medical Devices Regulations, if such test kits are available
through the accredited laboratory referred to in Clause 3.5.1.1(b),
or
- with diagnostic test kits that have been approved or licensed
under the Canadian Medical Devices Regulations, in any other case.
Note: It is appropriate risk management to use diagnostic test kits
on a temporary basis until donor screening tests are available and
licensed under the Canadian Medical Devices Regulations.
- The serological tests specified in Clause 3.5.3 should be performed
on a blood specimen obtained from the semen donor:
- with donor screening test kits approved or licensed under the
Canadian Medical Devices Regulations, if such test kits are available
through the accredited laboratory referred to in Clause 3.5.1.1(b),
or
- with diagnostic test kits that have been approved or licenced
under the Canadian Medical Devices Regulations, in any other case.
- Microbiological testing for Chlamydia trachomatis and Neisseria gonorrhoeae
shall be performed with test kits that have been approved or licenced
under the Canadian Medical Devices Regulations for the specimen being
tested, if such test kits are available through the accredited laboratory
specified in Clause 3.5.1.1 (b). The manufacturers' instructions for
the performance and interpretation of their tests and the manufacturers'
requirements for specimens shall be followed.
- If microbiological testing for Chlamydia trachomatis and Neisseria
gonorrhoeae is performed using a test or method developed by the accredited
laboratory specified in Clause 3.5.1.1(b), the laboratory must have
validation data to support the use of the test or method for the intended
application.
- Donors who test positive for any of the infectious disease markers
or infectious agents listed in Clauses 3.5.2, 3.5.4, 4.1.1, 4.2.2 (b),
5.1 and 5.2 must be rejected.
3.5.1.2 Notification Requirement
Positive results for the serological and microbiological tests specified
in Clauses 3.5, 4 and 5 shall be immediately reported in writing to the
donor by the semen bank or fertility clinic.
Note: Canadian semen processors should also report positive serological
and microbiological test results to the Public Health Authority as required
in the notifiable diseases reporting process under the applicable Public
Health Act and Regulations of each province and territory.
3.5.2 Minimum Serological Testing
Minimum serological testing shall include tests for:
- Antibody to HIV-1 and 2;
- Antibody to HCV;
- Hepatitis B surface antigen (HBsAg);
- Antibody to Hepatitis B core antigen (IgG anti-HBcAg);
- Antibody to HTLV-I and HTLV-II; and
- Treponema pallidum (syphilis)
- non-treponemal test; and ii. treponemal-specific test (FTA-ABS
or MHA-TP).
Note: Additional information on the laboratory diagnosis of syphilis
can be found in the Canadian STD Guidelines
3.5.3 Additional Serological Testing
Additional serological testing should include tests for Cytomegalovirus
(CMV) IgM & IgG.
Note: IgM positive donors should be deferred from donating semen
until they become IgM negative. CMV IgG positive donors should also be
deferred if any additional testing shows the presence of active infection
at the time of donation. CMV IgG positive donors should be used only for
CMV seropositive recipients. IgG negative donors may be used for CMV seropositive
or seronegative recipients.
3.5.4 Minimum Microbiological Testing
Minimum microbiological testing shall include:
- A test for Chlamydia trachomatis using a nucleic acid amplification
test on urine, urethral or semen specimens;
- A test for Neisseria gonorrhoeae using:
- urethral or semen cultures; or
- a nucleic acid amplification test on urine, urethral or semen
specimens; and
Note: Urine and urethral specimens for microbiological testing
should be collected and transported as described in the Canadian
STD Guidelines.
For the purposes of donor counseling and treatment, a positive nucleic
acid amplification test result should be confirmed using a different
set of primers to rule out false positive results.
Additional information on the laboratory diagnosis of Chlamydia
trachomatis and Neisseria gonorrhoeae infections can be found in
the Canadian STD Guidelines.
- A general semen culture and sensitivity evaluation.
Note: A positive test consists of any organisms not considered
normal flora.
3.6 Rh Status
The donor's Rh Status shall be determined at either the initial testing
stage, or at any time before the semen is released for distribution.
Note: In the case of an Rh negative recipient an Rh negative donor
should be used whenever possible.
3.7 Archived Serum Samples
A serum sample should be collected from the donor and cryopreserved for
retrospective testing when new tests are adopted for donor screening.
3.8 Semen Processed Prior to March 14, 2000
For semen processed prior to March 14, 2000, only the measures set out
in Clause 6 apply.
4. REPEAT SCREENING & QUARANTINE
4.1 Repeat Screening
4.1.1 Serological Testing
The minimum serological tests outlined in Clause 3.5.2 should be repeated
on new specimens obtained from the donor at least every 180 days while
the donor remains an active participant in the program, and after interruptions
exceeding 180 days.
4.1.2 Cytomegalovirus (CMV) IgM & IgG.
- Donors who tested positive for CMV IgG at the "Work-up"
stage need not be retested for CMV IgG.
Note: If other tests show the presence of active infection in a CMV
IgG positive donor, the donor should be deferred until the infection
is resolved.
- Donors who tested negative for CMV IgG or CMV IgM at the "Work-up"
stage should be retested every 180 days to detect seroconversion in
the donor.
Note: Seroconversion from a negative to positive IgG or IgM status on
retest implies an infection occurred shortly before the donor was recruited
or during the testing interval, and semen donated during this period should
be discarded.
4.1.3 Microbiological Testing
Repeat microbiological testing shall be performed at the time of each
donation, as specified in Clause 5.
4.1.4 Physical Examination
A physical examination of the donor should be conducted at least every
365 days while the donor remains an active participant in the program,
and after interruptions exceeding 365 days.
4.2 Quarantine and Repeat Screening
4.2.1 Quarantine Period
Fresh semen shall not be used for donor insemination. All donated semen
must be frozen and quarantined for a minimum of 180 days.
Note: The quarantine period is to allow for the detection of seroconversion
in the donor.
4.2.2 Repeat Screening Prior to Distribution
After the semen donation has been quarantined for a minimum of 180 days
but before it is distributed,
- The donor must be re-evaluated on the basis of the exclusion criteria
and still found not to be within a group set out under the heading "Exclusions"
in Clause 2;
- The minimum serological testing set out in Clause 3.5.2, with the
exception of 3.5.2(c), must be repeated on a new specimen obtained from
the donor; and
- Serological testing for CMV IgG and CMV IgM should be repeated where
the donor tested CMV IgG or CMV IgM negative at the "Work-up"
stage, using a new specimen obtained from the donor.
4.3 Evaluation of Semen Safety
4.3.1 Role of the Medical Director or Physician
Designated by the Medical Director
The Medical Director, who is responsible for the overall medical care,
or his or her Physician Designate, shall determine and document whether
semen may be released for distribution following a review of:
- Screening based on the exclusion criteria set out under the heading
"Exclusions" in Clause 2;
- Donor infectious disease screening by serological and microbiological
testing performed during the "Work-up" stage, as required
under Clauses 3.5.2 and 3.5.4;
- Donor infectious disease screening by serological testing performed
during the repeat testing, as required under Clause 4.2; and
- Microbiological testing performed as set out in Clauses 5.1 and 5.2.
4.3.2 Semen Release
Evaluation of the safety of the tested semen shall be confirmed prior
to the semen being released for distribution.
4.4 Semen Processed Prior to March 14, 2000
For semen processed prior to March 14, 2000, only the measures set out
in Clause 6 apply.
5. MICROBIOLOGY
5.1 Chlamydia trachomatis and Neisseria gonorrhoeae
A specimen collected from the donor at the time of each donation shall
be tested for Chlamydia trachomatis and Neisseria gonorrhoeae as specified
in Clauses 3.5.4 (a) and (b).
5.2 General Culture and Sensitivity Evaluation
Semen cultures for each donation shall include a general culture and
sensitivity evaluation.
Note: A positive test consists of any organisms not considered
normal flora.
5.3 Antibiotics
If antibiotics are included in the cryoprotectant medium formulation,
it should be documented because of possible antibiotic sensitivity or
allergy in recipients.
5.4 Semen Processed Prior to March 14, 2000
For semen processed prior to March 14, 2000, only the measures set out
in Clause 6 apply.
6. SEMEN PROCESSED PRIOR TO MARCH 14, 2000
6.1 Exclusion Criteria
- For semen fully processed prior to March 14, 2000, the criteria set
out under the heading "Exclusions" of the CFAS 1996 Guidelines
or those set out in Clause 2.1 of this Directive must have been applied.
- If, prior to March 14, 2000, semen has been collected but the repeat
screening after a minimum quarantine period of 180 days has not been
done, the repeat screening must be done in accordance with the criteria
set out under Clause 2.1.
6.2 Serological Testing
6.2.1 Work-Up
For semen processed prior to March 14, 2000, the following minimum serological
tests must have been performed at the "Work-up" stage:
- Antibody to HIV-1 and 2;
- Antibody to HCV;
- Hepatitis B surface antigen (HBsAg);
- Antibody to HTLV I and II; and
- Treponema pallidum (syphilis) using
- non-treponemal test; or
- treponemal-specific test (FTA-ABS or MHA-TP).
6.2.2 Repeat Screening and Quarantine
6.2.2.1 Fully Processed Semen
For semen fully processed prior to March 14, 2000, the following tests
must have been performed:
- Minimum serological testing performed at least every 180 days while
the donor remained an active participant in the program must have included
tests for:
- Hepatitis B surface antigen (HBsAg), unless the test for antibody
to Hepatitis B core antigen (IgG anti-HBcAg) was done after a minimum
quarantine period of 180 days; and
- Treponema pallidum (syphilis) using a non-treponemal test or
a treponemal-specific test (FTA-ABS or MHA-TP), unless both the
non-treponemal test and the treponemal-specific tests were done
after a minimum quarantine period of 180 days; and
- Minimum serological testing performed after the semen was quarantined
for a minimum of 180 days but before distribution must have included
tests for:
- antibody to HIV-1 and 2;
- antibody to HCV;
- hepatitis B surface antigen (HBsAg) or antibody to Hepatitis
B core antigen (IgG anti-HBcAg);
- antibody to HTLV I and II; and
- Treponema pallidum (syphilis) using:
- non-treponemal test; or
- treponemal-specific test (FTA-ABS or MHA-TP).
6.2.2.2 Partially Processed Semen
If, prior to March 14, 2000, semen has been processed but the repeat
testing after a minimum quarantine period of 180 days has not been done,
the repeat testing must be done in accordance with the requirements set
out under Clause 4.2.2.
6.3 Microbiology
- For semen processed prior to March 14, 2000, the following minimum
microbiological tests must have been performed at the "Work-up"
stage and at least every 180 days while the donor remained an active
participant in the program:
- Chlamydia trachomatis using a nucleic acid amplification test
on urine or urethral specimens; and
- Neisseria gonorrhoeae using
- urethral or semen cultures; or
- a nucleic acid amplification test on urine or urethral specimens.
- For semen processed prior to March 14, 2000 in respect of which the
testing for Chlamydia trachomatis specified in clause 6.3(a)(i) has
not been done, a nucleic acid amplification test for Chlamydia trachomatis
must be performed:
- on a semen specimen from the same donation as the semen that
is to be distributed; or
- on semen specimens from two donations made within 180 days of
each other by the donor of the semen that is to be distributed,
one of which was made before the donation of the semen that is to
be distributed and one of which was made after that donation.
- For semen processed prior to March 14, 2000 in respect of which the
testing for Neisseria gonorrhoeae specified in clause 6.3(a)(ii) has
not been done, a nucleic acid amplification test for Neisseria gonorrhoeae
must be performed:
- on a semen specimen from the same donation as the semen that
is to be distributed; or
- on semen specimens from two donations made within 180 days of
each other by the donor of the semen that is to be distributed,
one of which was made before the donation of the semen that is to
be distributed and one of which was made after that donation.
Note: Semen shall not be released for distribution if cultures rather
than nucleic acid amplification tests were used for the detection of
Chlamydia trachomatis.
- For semen processed prior to March 14, 2000, specimens collected
between testing intervals in which Chlamydia trachomatis or Neisseria
gonorrhoeae infection cannot be ruled out must be discarded.
6.4 Other Measures
In respect of matters other than testing for infectious diseases, semen
processed prior to March 14, 2000 must have been processed in accordance
with either:
- The measures set out under the headings "Work-Up", "Repeat
Screening & Quarantine" and "Semen Microbiology"
of the CFAS 1996 Guidelines; or
- The measures set out under the headings "Work-Up", "Repeat
Screening & Quarantine" and "Microbiology" of this
Directive.
7. ADDITIONAL INFORMATION
Questions concerning this Directive should be directed in writing to:
Blood and Tissues Division
Bureau of Biologics and Radiopharmaceuticals
3rd Floor LCDC Building #6
Postal Locator 0603C3, Tunney's Pasture
Ottawa, Ontario KIA 0L2
Facsimile: (613) 941-5841
Email: francisca_agbanyo@hc-sc.gc.ca
Attention: Francisca Agbanyo, PhD
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