Quality is the Key to Reliable IVF
Product quality is the single most important
criteria when selecting an IVF products partner. Due to our
stringent testing and medical devices certification, using
Thermo Scientific Nunc IVF products ensures that you receive the
most consistent high quality products.
All Nunc products are manufactured under an ISO 13485-registered
system to ensure consistent quality. All of our IVF products are
extensively tested.
Mouse Embryo Assay (MEA) test
We use the 1-cell stage mouse embryo toxicity test.
The standard requirement is for 70% of the fertilized eggs to
develop to fully expanded blastocysts in order for product to pass
the MEA test. Our requirement is for at least 80% of the fertilized
eggs to develop to fully expanded blastocysts to pass the MEA test.
Our elevated acceptance level assures the safety of your work. This
embryo-toxicity test is a release test and only product that has
passed the test will be sold.
MEA test protocol:
Embryos from B6C3F1xB6D2F1 mice are used (B6C3F1
female mice mated with B6D2F1 male mice).
Direct test: Embryos are cultured in a dish
with 21 embryos in triplicate. Three of the four wells receive seven
1-cell stage embryos in 0.5 ml of medium. Incubation is done at 37°
C and 5% CO2. Performance is observed at 24 and 96 hours. After 24
hours the number of embryos that have developed to the 2-cell stage
is recorded. After 96 hours the embryos that have reached the
expanded blastocyst stage are scored as being viable. At least 80%
of the 1-cell test embryos must develop to the expanded blastocyst
stage.
Indirect test: 0.5 ml "embryo-tested" (previously
embryo-tested medium) culture medium is placed in a dish for 48
hours at 37° C and 5% CO2. The media is retracted and 21 1-cell
embryos are cultured in triplicate in 12 µl droplets of the
resulting media extract supplemented with 0.4% BSA.
Frequent questions on the MEA test
Why is the 1-cell stage test chosen?
The test was chosen after consulting IVF clinics and
Embryotech. This test is an effective measure of both
reproducibility and sensitivity. We have chosen the 1-cell stage
test since it is considered more sensitive than the 2-cell stage
test favored by other manufacturers.
Why are 21 embryos tested?
The choice was made after consulting Embryotech. 21
embryos provide a sample large enough to detect toxicity. By using
this large number there are likely to be fewer lots rejected based
on spontaneous deaths (false positive) results in the MEA test.
Why an 80% blastocyst formation criteria?
This value was chosen based on dialogue with experts
in this field in order to ensure the most stringent criteria on the
market. Normal test criteria is 70%.
Which criteria are used when an embryo is
selected and evaluated?
We utilize Embryotech as an external independent
testing facility. They use the same criteria for us that they use
when performing control assays for IVF clinics.
Why don’t we do the testing ourselves?
Outside consultants who are experts in the IVF field
are better-equipped to assure non-biased and dependable tests, and
to avoid any question of objectivity.
Human Sperm Motility BioAssay test (HSSA test)
To pass the HSSA test, the motility of human sperm
should be ≥70% after 24 hours of sample preparation. The control
sample motility must be at least 50% of the initial swim-up motility
for the test to be acceptable. The HSSA test is a release test and
the product will only be sold if it has passed satisfactorily. Not
all competitors’ products are tested using the HSSA test.
Certificates
We provide two
kinds of certificates
Product Certificates are available in all cases.
Certificates of Analysis specific for each lot are available on
request or as download (Link to example).
Results of the MEA and HSSA tests are reported on the lot specific
Certificate of Analysis, together with certification of
non-pyrogenicity (LAL test), sterility (ISO 11137), non-cytotoxicity,
non-mutagenicity (Ames test) and production according to ISO 13485
and ISO 9001.
For user name and password contact our QA/QC department on:
certificate.nunc@thermofisher.com
Download site is:
http://certificates.nunc.dk
For any inquiries regarding certificates contact:
certificate.nunc@thermofisher.com
Full Lot Control
Thermo Fisher Scientific quality guidelines dictate
full lot control of the raw material to ensure that no variation in
cytotoxicity in the batch of polystyrene will be transmitted. Also,
a complete lot is irradiated simultaneously in order to minimize
variation. This stringent lot control ensures that test results
achieved represent the cytotoxicity level for all the products in
the manufacturing lot.
LAL test
LAL is short for Limulus Amoebocyte Lysate and is an aqueous
extract of blood cells (amoebocytes) from the horseshoe crab,
Limulus Polyphemus. LAL reacts with bacterial endotoxin or
lipopolysaccharide, which is a membrane component of
gram-negative bacteria. This reaction is the basis of the LAL
test, which is used for the detection and quantification of
bacterial endotoxins. Many species of gram-negative bacteria are
pathogenic, meaning that they can cause disease in a host
organism. Therefore it is important to make sure that products
are not contaminated with bacterial endotoxins.
(Horseshoe crabs can be seen on the eastern US coast, the east
coast of India, as well as in inland seas in Japan. They are
considered near endangered).
ISO 11137
ISO 11137-1:2006 specifies requirements for the development,
validation and routine control of a radiation sterilization
process for medical devices.
Ames tested for mutagenicity
The Ames test is a biological assay used to assess whether
chemical compounds can cause mutations. The test uses strains of
the bacterium Salmonella Typhimurium that carry mutations in
genes involved in histidine synthesis, so that they require
histidine for growth. The bacteria are spread on an agar plate
with a small amount of histidine. This small amount of histidine
in the growth medium allows the bacteria to grow for an initial
time and have the opportunity to mutate. When the histidine is
depleted, only bacteria that have mutated to gain the ability to
produce its own histidine will survive. The plate is incubated
for 48 hours. The mutagenicity of a substance is proportional to
the number of colonies observed.
The test is named after Bruce Ames from the University of
California who described this test method in the early 1970s.
CE Mark
By providing the appropriate 4-digit code
representing our CE notified body below the CE mark on all our IVF
products, we guarantee to you that Nunc IVF products are
manufactured to the medical device directive class II.
FDA clearance
In order to sell Class II Medical Devices in the
USA, a product needs to be cleared for sale by the Federal Drug
Administration (FDA). Products for human IVF are described in
subchapter H, 884.6160 Assisted Reproduction Labware. Products in
this group require special controls such as MEA testing results
before the FDA will allow marketing of the products in USA.
We sell most of our products in the USA
ISO
13485
In order to utilize the CE mark on products, (either
according to the IVD or medical device directive) the production
facility has to be ISO 13485 registered. This is the ISO standard
used by the medical device and In Vitro diagnostics industry. In
order to obtain ISO 13485 registration we shall, among other
requirements, have:
-
Awareness of regulatory requirements (an example
of the market specific regulatory requirements is 21 CFR 820
Quality System Regulation for Medical Devices sold in the United
States)
-
Controls in the work environment to ensure
product safety
-
Focus on risk management activities and design
transfer activities during product development
-
Requirements for inspection and traceability for
devices
-
Requirements for documentation and validation of
processes for sterile medical devices
USP class VI
United States Pharmacopeia (USP) is an official
public standard–setting authority for all prescription medicines and
other health care products manufactured or sold in the United
States. USP sets standards for the quality, purity, strength, and
consistency of products critical to the public health.
The purpose of the USP class VI test is to determine the biological
response of mammalian cell cultures to direct and indirect contact
with plastics used for medical devices. The USP class VI test is
performed on the Polystyrene (BASF 158K) used in our production of
IVF products.
Plastics can be graded Class I to VI (1 to 6). Class VI is thus the
highest with most extensive testing also used for plastic for
implantable devices. Description can be found the general chapters
Biological Reactivity Tests, In Vitro <87> and Biological Reactivity
Tests, In Vivo <88> in the US Pharmacopeia
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