Quality Control

All media are Bovine Embryo Assay, BEA tested in addition to MEA prior to release

ARTS Media Denmark - Quality Control

Mouse Embryo Assay, MEA test is the legal requirement for release of new media batches, however, The Bovine Embryo Assay (BEA) test is an extremely important addition!

There are huge differences in reproductive physiology between the mouse and a woman, obviously also between a cow and a woman. The most obvious similarity in cow and woman is gestation time and that they don’t give birth to litters like mice.

However, the MEA test is considered sufficient for quality control release of ART media. When media are tested in the BEA, that all have passed MEA, they often give significantly different blastocyst rates as well as considerable morphologic and kinetic differences in the BEA test.

In vitro oocyte maturation (IVM) , is at the moment not a standard procedure in human ART as it is and has been for decades in bovine ART. Therefore the BEA test includes quality control of all steps of the procedure, IVM, IVF and IVC,

In addition, fertilization and capacitation are species specific and a MEA test mostly assesses blastocyst development from either one-cell or two-cell stage embryos. Should a batch variation occur it will not be detected in a MEA test, where release parameter is > 80 % blastocyst rate. In the BEA test, however, a difference in medium quality can be detected even though the medium has passed the MEA test. For instance, 35 % vs 55 % blastocyst rates indicate two media are different, however both media will have passed the MEA. Hence, the MEA is a mere toxicological bio-assay, whereas the BEA also provides functional and performance data.

Therefore, we have decided that every single batch manufactured will undergo the BEA test in addition to the required MEA Test.

How is the BEA test conducted?

Ovaries from slaughterhouse cows are collected and in the laboratory the oocytes are aspirated from all follicles size 10 mm-35 mm. Approximately 8 oocytes per ovary is on average obtained. They are subsequently matured, fertilized and cultured. Each new medium is tested in a control group with a minimum 150 oocytes per group. Blastocyst rates and kinetics and morphology are evaluated as well as hatching rates. The average blastocyst rates in the BEA test are between 40-50% and thus indicate performance differences, whereas  80 – 90 % blastocyst rates in the MEA test only indicate whether  the medium is toxic or not.

Plastic vs Glass bottles

Only in glass bottles can you maintain stability of the active compounds in the media for up to 18-24 months. Plastic will decrease quality of media over time and even contribute to toxicity and will always have a limited shelf-life. The entire batch must be manufactured in one day. That means that no stock solutions should be stored for a longer period of time and that the entire batch should be manufactured and bottled within the same day and not stored overnight.

Batch Certificate

Every single batch should always come with a batch certificate stating that sterility, fungal and endotoxin tests have been performed and passed quality control specifications. For some products pH will be measured, but it doesn’t make sense to have a set pH value release criterion for pH, if the buffer is CO2 calibrated with bicarbonate.

More similarities and differences

Based on:

Virtues and limitations of the preimplantation mouse embryo as a model system

Robert A Taft Theriogenology.

Read the full article here: https://doi.org/10.1016/j.theriogenology.2007.09.032

Or feel free to contact us

Comparison of embryo development in human, cow and mouse.
Human
Cow
Mouse
Oocyte diameter (μm)
110-120
120
70-90
Stage at zygotic genome activation
4-8  cell
8-16 cell
2-cell
Time to reach
2-cell stage (hours)
30
36
18-20
Blastocyst (hours)
120
150
70
Hatching (hours)
150
200
100
Implantation (days)
9
21
4

Mouse and bovine models for human IVF, December 2002,  Reproductive Biomedicine Online 4(2):170-5
DOI:10.1016/S1472-6483(10)61936-0

Amino acid

Amino acid uptake and utilization also differ among species with mouse embryos not requiring amino acids to develop to the blastocyst stage, in contrast to bovine and human embryos

pH

Mouse embryos are less sensitive to and recover more easily from changes in pH than either human or bovine embryos

Glucose

The ability to utilize glucose varies among species. Human embryos do not utilize glucose due to limited availability of hexokinase. The situation is more complicated for the mouse, as embryos from some strains can metabolize glucose while others cannot. Cattle embryos are able to metabolize glucose, although this is affected by culture conditions .

The strains of mice and developmental stage

Some of the controversy regarding the perceived value of the mouse embryo assay is likely the result of the conditions under which the assay was conducted. The strain of mouse used, stage of embryo used and the culture conditions employed may also affect the outcome. Thus, embryos from inbred strains may provide a better model, and the developmental stage of the embryo will also impact the result. For instance,  one-cell embryos are more sensitive than two-cell, four-cell or eight-cell embryos.

Finally, the type of media also influences the assay. For instance the absence of protein in the media improves the sensitivity of the assay.

Manufacturing

Our factory is ISO13485 certified
  • Each batch of medium comes with a certificate for BEA test as well as sterility, fungal and endotoxin tests
  • The production site is ISO9001 and ISO13485 certified
  • All media are delivered in glass bottles

ISO standards are internationally agreed by experts and when a factory is certified it ensures state-of-the-art manufacturing in a controlled environment and is your assurance of quality.

ISO 13485, also known as the medical device regulatory system, is a quality system for the medical device industry. It also means that the factory is audited through the Medical Device Single Audit Program(MDSAP) .

MDSAP is a program that allows the conduct of a single regulatory audit of the  manufacturer’s quality management system that satisfies the requirements of multiple regulatory jurisdictions.

A MDSAP audit assures compliance with the standard and regulatory requirements of up to five different medical device markets: Australia, Brazil, Canada, Japan and the United States.

The MDSAP was developed by representatives of the Australian Therapeutic Goods Administration (TGA), Brazil’s Agência Nacional de Vigilância Sanitária (ANVISA), Health Canada, MHLW/PMDA, and the U.S. Food and Drug Administration (FDA). All regulatory authorities participating in the MDSAP are equal partners in the program.

ARTS Media Denmark - Manufacturing