Fetal Bovine Serum is derived from the blood of fetuses of slaughtered dams which have passed ante and post mortem veterinary inspection in government supervised slaughter-houses and are passed as fit for human consumption. The blood is obtained by cardiac puncture utilising a single-use needle, tube and bag.
The blood is allowed to clot naturally and is then centrifuged to obtain the liquid fraction of the blood which is now regarded as semi-processed serum. No other additions or deletions of material are permitted.
STERILE FILTERED: Semi-processed Raw Fetal Bovine Serum, is thawed, pooled and filtered through a series of sterile membranes down to 0.1 microns before being finally packaged, usually in 500ml or 1L bottles. No further processing, additions or deletions are performed. However, subsequent treatment, including gamma irradiation or heat inactivation, may be carried out and the bottles labelled accordingly.
Moregate Biotech offers and performs or facilitates a range of treatments of our basic products, either as stock standard or to specific customer requirements. These treatments include gamma irradiation, heat inactivation and/or other modifications as required.
|Available Treatments - Fetal Bovine Serum - Sterile Filtered (FBSF)|
|IRRADIATED||Gamma Irradiation of Sterile Filtered FBS takes place in Brisbane at an Australian Government licensed gamma irradiation facility. Frozen serum is irradiated following Moregate Biotech's validated procedure to a customer specified dose range. A gamma irradiation indicator (colour change) is applied to every container before irradiation. A Certificate of Irradiation is issued for every lot of irradiated serum.|
|HEAT INACTIVATED||Heat Inactivation of sterile filtered serum is achieved following Moregate Biotech's validated process. This is performed at our Brisbane production facility. A Certificate of Heat Inactivation is issued for every heat inactivated lot of serum.|
|Specification - Fetal Bovine Serum - Sterile Filtered (FBSF)|
|Product||Fetal Bovine Serum - Sterile Filtered|
|Certificate of Suitability||Australia: R1-CEP 2000-187-Rev 00 New Zealand: R1-CEP 2000-188-Rev 00|
|Source||Bovine blood from fetuses of healthy cows which have been inspected ante and post mortem by Australian or New Zealand Government veterinarians and passed as fit for human consumption.|
|Collection/Processing Method||Blood is collected via cardiac puncture into sterile bags. Blood is separated by cup centrifugation and double spun. Serum is subsequently passed through a series of filters terminating with triple 0.1 µm pore size filters. Product is dispensed in IS0 14644 Class 5 Laminar Flow Workstation via a closed system. It is then immediately frozen.|
|Description||A clear amber viscous liquid with a characteristic odour.|
|Pack Size||500ml & 1000ml sterile PET & PETG square media bottles|
|Storage||-20 degrees Centigrade|
|Expiry Date||Six years from the date of manufacture|
|Visual Examination||Visual Examination||Satisfactory|
|Sterility||Millipore Steritest Broth Culture 14 Day Incubation||Sterile|
|Mycoplasma||Broth Culture 35 Day Incubation||Not Detected|
|pH||pH Meter||6.9 - 7.6|
|Total Protein||Beckman Coulter Synchron Clinical Systems||30 - 45 mg/m|
|Albumin||Electrophoresis||As Reported %|
|IgG||ELISA||≤ 400 mg/l|
|Electrophoresis pattern||Agarose Gel Plate||Typical|
|Haemoglobin||UV/VIS Spectrophotometer||≤ 0.18 mg/ml|
|Endotoxin||Kinetic Turbidimetric||≤ 5 IU/ml|
|Cell Line Used|
|Biochemical Profile - Beckman DXC 800 Analyser|
|Sodium||As Reported mmol/l|
|Potassium||As Reported mmol/l|
|Chloride||As Reported mmol/l|
|Bicarbonate||As Reported mmol/l|
|Anion Gap||As Reported mmol/l|
|Glucose||As Reported mmol/l|
|Urea||As Reported mmol/l|
|Creatinine||As Reported µmol/l|
|Urea/Creatinine||As Reported (ratio)|
|Urate||As Reported mmol/l|
|Bilirubin total||As Reported µmol/l|
|Calcium||As Reported mmol/l|
|Alkaline Phosphatase||As Reported U/l|
|Gamma Glutamyl Transferase||As Reported U/l|
|Alanine Transaminase (Glutamic Pyruvic Transaminase)||As Reported U/l|
|Aspartate Transaminase (Glutamic Oxaloacetic Transaminase)||As Reported U/l|
|Lactate Dehydrogenase||As Reported U/l|
|Cholesterol||≤ 1.2 mmol/l|
|Triglyceride||As Reported mmol/l|
The European Pharmacopeia consists of a number of general and specific monographs covering various classes of products.
The monographs set out requirements to be met and followed for all products in the class.
Recently the EP has introduced a Monograph for Bovine Serum – Monograph No 04/2006:2262 to be found in E.P. 5.4
This monograph provides a definition of Bovine Serum and sets out details of production, and requirements for viral inactivation parameters, quality control testing, storage conditions and labelling.
Moregate Bovine Serum products meet these requirements and Certificates of Analysis are modeled on the QC test requirements.
The United States Pharmacopeia-National Formulary (USP-NF) contains standards for medicines, dosage forms, drug substances, excipients, medical devices, and dietary supplements.
Within the Pharmacopeia are Monographs and general chapters.
The monographs consist of information such as the ingredient name, definition, packaging and labelling requirements, storage and a specification.
The specifications list tests to be performed along with the procedure to be followed and the acceptable limit.
The European Medicines Agency (EMEA) is a decentralised body of the European Union with headquarters in London. It sits alongside the European Directorate for the Quality of Medicines (EDQM).
The main responsibility is the protection and promotion of public and animal health, through the evaluation and supervision of medicines for human and veterinary use.
The EMEA publishes guidelines on quality, safety and efficacy testing requirements.
These guidelines are prepared by committees, and those guidelines which relate to the use of Bovine Serum, including Fetal Bovine Serum, in the manufacture of medicines include:
CPMP: Committee for Proprietary Medicinal Products
Note for Guidance on the Use of Bovine Serum in the Manufacture of Human Biological Medicinal Products
Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products. (Also adopted by the CVMP)
CVMP: Committee for Veterinary Medicinal Products
Requirements and Controls applied to Bovine Serum used in the production of Immunological Veterinary Medicinal products.
These Guidelines include requirements for Virus Testing of Fetal Bovine Serum and other Bovine Serum. Further reference to these requirements can be found in “Virus Testing”.
All Moregate Biotech Fetal Bovine Serum and other Bovine Serum meet the requirements of the Guidelines in relation to Fetal Bovine Serum and Bovine Serum.
Ingredients of animal origin used in the United States of America, in the manufacture of veterinary and human biologics are required to be in compliance with the Code of Federal Regulations, Title 9 – Animals and Animal Products, Chapter 1 - Animal and Plant Health Inspection Service, Department of Agriculture Part 113-53c, commonly referred to as 9CFR Part 113-53c.
This legislation sets out the requirements for detection of extraneous viruses, detailing the methods to be used and the list of viruses that shall be tested for.
Over time 9CFR Part 113-53c became the accepted standard for the testing of animal sera, particularly Fetal Bovine Serum for adventitious viral agents.
Bovine Respiratory Syncytical Virus, Bovine Viral Diarrhea Virus, Bovine Parvovirus, Bluetongue Virus, Bovine Adenovirus, Rabies Virus and Reovirus are tested for by fluorescent antibody
Infections Bovine Rhinotracheitis tested for by Cytopathic Agents.
Infectious Influenza 3 tested for by Haemadsorbing Agents
The European Directorate for the Quality of Medicines (EDQM) has originated from the European Pharmacopoeia Secretariat which, with the addition of new responsibilities changed its name to the European Department for the Quality of Medicines (EDQM). The EDQM sits alongside the European Medicines Agency (EMEA).
Amongst other activities, the EDQM is responsible for the European Pharmacopeia and the issuing of Certificates of Suitability (CEP).
Certificates of Suitability (CEP) are recognised by all signatory states of the European Pharmacopoeia Convention and by the European Union. Other countries have also chosen to recognise them. In the case of Fetal Bovine Serum and other Bovine Serum a CEP can be used by the manufacturers of Fetal Bovine Serum and other Bovine Serum which is intended for use in the manufacture of pharmaceutical products to demonstrate compliance with the Bovine Serum monographs of the European Pharmacopoeia and the EDQM requirements for substances concerned by TSE risk.
The discovery of Bovine Spongiform Encephalopathy (BSE), which is one of a group of similar infections now referred to as Transmissible Spongiform Encephalopathies (TSEs), and it’s spread over many countries of the European Union as well as its discovery in Canada, the USA and Japan is well known. The European events provided the impetus for the Council of Europe Public Health Committee (CEPHC) to pass Resolution AP-CSP (99) 5 addressing the TSE concerns and creating a Certificate of Suitability (COS) pursuant to Directive 75/318/EEC.
The granting of a CoS to a manufacturer, for a particular product, certifies that the product in question has been assessed for the level of risk of transmission of TSEs, and that the risk level is considered low enough that the product is certified as suitable for use in the manufacture of medicinal products in the European Union.
The process of approval requires the manufacturer to submit a dossier that covers all relevant aspects of the collection of raw material and further processing that is performed to reach the product that is offered to end users. This dossier is detailed and covers the specific material that is collected, the collection method, process validation, testing, traceability, quality systems and an expert review.
Only after this dossier has been examined and approved by two rapporteurs and, if necessary, by a panel of experts appointed by the European Directorate for the Quality of Medicines (EDQM) is the manufacturer granted a COS.
Moregate Biotech has been granted a COS for:
- Fetal Bovine Serum – Australian Origin – CEP2000-187
- Fetal Bovine Serum – New Zealand Origin – CEP2000-188
- Adult Bovine Serum - New Zealand Origin – CEP2001-093
- Adult Bovine Serum (Defibrinated) - New Zealand Origin – CEP2000-174
- Bovine Plasma – New Zealand Origin – CEP2003-199
- Bovine Serum Albumin – manufactured in Australia from New Zealand origin Bovine Plasma – CEP2003-205
- Bovine Plasma – Australian Origin - CEP 2005-192
- Bovine Serum Albumin – manufactured in Australia from Australian origin Bovine Plasma - CEP 2005-191
Copies of the Certificates of Suitability are available upon request
SPECIAL INDICATION OF HAZARDS TO HUMANS AND THE ENVIRONMENT
First Aid Measures
Get Medical attention immediately.
If swallowed, give several glasses of water to drink to dilute.
Wash skin with soap and copious amounts of water.
Flush with water for at least 15 minutes, lifting upper and lower eyelids occasionally.
Procedures for Personal Precaution
Exercise appropriate precautions to minimize direct contact with skin or eyes.
Methods for Cleaning Up
Ventilate area and wash spill site after material pickup is complete
Avoid contact with eyes, skin and clothing.
Keep tightly closed. Store at -20 °C.
Contact a licensed professional waste disposal service to dispose of this material.
Note: The above information is believed to be correct, but shall be used as a guide only.
Disclaimer: For pharmaceutical use only.
Moregate Fetal Bovine Serum FBS is manufactured from Fetal Blood collected using a closed system.
Constant supervision ensures the cold chain is rigorously maintained.
Blood collected is immediately chilled and kept at 3 - 7°C throughout the production process.
The collection bags are chilled in ice slush and then transported covered with specially chilled packs. The blood temperature is monitored and recorded when the Fetal Blood is received at the processing facility.
The FBS laboratory is temperature controlled and supplied with HEPA filtered air. The laboratory space itself is protected by airlocks.
The centrifuges used for separation are refrigerated and the finished raw FBS is immediately frozen at -20°C.
Sterile Fetal Bovine Serum is finished in a laboratory area operated to cGMP standard. All production processes are performed and recorded to an ISO 9001:2008 system.
Raw Fetal Bovine Serum is thawed under temperature controlled conditions and pooled under a laminar flow HEPA filter.
Filtration is carried out using a two tank system to ensure complete homogeneity. Pooled serum is transferred via pre filters to a Raw Serum tank. This pool is stirred constantly by a magnetic stirrer.
The finished sterile serum is held in the Sterile Serum tank until the filtration is complete. The serum is constantly moved by a magnetic stirrer to ensure complete homogeneity before dispensing.
The entire filtration and dispensing system including both tanks are sterilised using pure steam.
Final filtration is by triple 0.1 micron filters for Fetal Bovine Serum.
Dispensing is done within a ISO 14644 Class 5 workstation placed in a Class 7 clean room. The air supply is pressurised with pressures descending from the Class 7 clean room outwards.
Environmental monitoring is performed during the filling operation. The atmosphere is monitored for viable and non viable particles. Both work room surfaces as well as personnel are checked for bacterial levels.
All operations are performed and recorded according to ISO 9001:2008 Quality System.
Protection is provided by airlocks and equipment/personnel ingress/egress. These airlocks lead from the class 7 clean room into another clean room, also protected by airlocks.
Finished sterile FBS is blast frozen and stored at -20°C