Species Specific Viruses
Meeting Your Species-Specific Virus Testing Needs
Manufacturing biologic products poses an inherent risk for the introduction of viruses, both during the process and from the product itself. Drug developers and manufacturers must be diligent in risk assessment, perpetually reviewing the entire production process to identify any possible opportunity for viral contamination.
In this effort, manufacturers should have a dedicated strategy in the assessment of cell lines or viral seed stocks the biologics are derived from, or any raw materials of animal origin being introduced into the process.
Sartorius’ experts consult of which assays should be used, and can design and validate custom assays to your exact requirements providing a comprehensive strategy for species-specific virus testing:
Ready-to-use PCR packages for panels of viruses derived from human, simian, bovine or porcine origin
Ready-to-use single-species testing for common contaminants such as murine minute virus (MMV) (also known as Minute Virus of Mice – MVM) or emerging virus risks such as SARS-CoV-2.
For biologics produced from rodent cell lines such as CHO and BHK-21, specific antibody tests are required.
Our scientific and regulatory experts build a species-specific virus testing plan tailored to your drug development or commercial product needs
Ready-to-use, quality-assured testing plans and prevalidated cGMP tests allow immediate access to specialized testing and faster results
Ensure a comprehensive viral biosafety profile for your product with customized PCR methods and validation to provide cGMP compliant viral detection assays tailored to your needs
Our cGMP-compliant assays align with European Pharmacopeia (EP) and United States Pharmacopeia (USP) guidelines
A Focus on Species-Specific Virus Testing
Species specific virus testing is required predominantly on biological starting material (master cell bank and master viral seed stock) and during manufacturing at the unpurified bulk harvest and end of production cell bank. The viral panel is based on the cell line type along with a risk-based QC testing plan aligned with global regulations.
The below table is for illustrative purposes only.
Sampled from | Bovine and Porcine Viral Panel | Human Virus Panel | Simian Virus Panel | MVM Virus | MAP & HAP |
|---|---|---|---|---|---|
Research Cell Bank | - | - | - | - | - |
Master Cell Bank | X1 | X2 | X2 | X3 | X3 |
Working Cell Bank | - | - | - | - | - |
End of Production Cell Bank | X1 | X2 | X2 | - | - |
Master Virus Seed stock | X1 | X2 | X2 | - | |
Working Virus Seed Stock | - | - | - | - | - |
Unpurified Bulk Harvest | X1 | X2 | X2 | X3 | X3 |
Drug Substance | - | - | - | - | - |
Drug Product | - | - | - | - | - |
X1 - Required for all cell lines involving bovine serum or porcine trypsin
X2 – Required for cell lines of human or simian origin
X3 – Required for cell lines of rodent origin
Bovine and Porcine Assays
Bovine Virus Detection
The Code of Federal Regulations (9CFR) includes a guideline for the testing of bovine serum in the production of a biologic. The regulation lists the specific viruses which could contaminate a serum batch:
Bovine viral diarrhoea virus (BVDV)
Bovine adenovirus type 5 (BAdV5)
Bovine parvovirus (BPV)
Bluetongue virus (BTV)
Bovine respiratory syncytial virus (BRSV)
Rabies virus
Reovirus type 3 (REO-3)
Bovine Parainfluenza type 3 virus (BPiV3).
Sartorius offers a sensitive PCR assay for the detection of these bovine viruses.
European regulations for the testing for bovine virus contamination also require examination for Bovine polyoma virus, for which Sartorius also offers a sensitive PCR assay.
Porcine Virus Detection
The Code of Federal Regulations (9CFR) includes a guideline for the testing of porcine-derived products in the production of a biologic. The regulation lists the specific viruses which could contaminate a batch:
- Bovine viral diarrhoea virus (BVDV)
- Rabies virus
- Reovirus
- Porcine parvovirus (PPV)
- Porcine adenovirus (PAdV)
- Porcine transmissible gastroenteritis virus (PTGV)
- Porcine hemagglutinating encephalomyelitis virus (PHEV)
The guideline also notes that if the porcine derived material is trypsin (which is common in recombinant protein production) then the testing requirement is only for Porcine parvovirus.
Sartorius offers a sensitive PCR assay for the detection of these viruses.
Rodent
Murine minute virus is a mouse parvovirus often detected in biologics involving Chinese hamster cell substrates. It is therefore recommended as a species-specific test when testing CHO cell lines or products due to the high risk of contamination.
Vesivirus 2117 (Caliciviridae) is an adventitious agent that was identified as a contaminant of CHO cells in 2009. It is therefore recommended as a species-specific test when testing CHO cell lines or products due to the high risk of contamination.
Sartorius offers sensitive PCR assays for each of these viruses.
MAP and HAP
Antibody Production Tests
Species-specific viruses present in rodent cell lines may be detected by inoculating test article into virus-free animals and examining the serum antibody level or enzyme activity after a specified period.
Examples of such tests are the Mouse Antibody Production (MAP) test and Hamster Antibody Production test (HAP).
The viruses detected in the MAP test include:
- Ectromelia virus (ECTV)
- Lymphocytic choriomeningitis virus (LCMV)
- Hanta viruses (HTNV)
- Pneumonia Virus of Mice (PVM)
- Reovirus Type 3 (REO)
- Theiler’s murine encephalomyelitis virus (TMEV)
- Lactic dehydrogenase virus (LDV)
- Sendai virus (SenV)
- Minute virus of mice (MVM)
- Mouse adenovirus (MAV 1 and 2)
- Mouse cytomegalovirus (MCMV)
- Mouse hepatitis virus (MHV)
- Mouse rotavirus/epizootic diarrhea of infant mice (EDIM)
- Polyoma virus (PYV)
- Mouse thymic virus (MTLV)
- K virus
Viruses detected in the HAP test include:
Lymphocytic Choriomeningitis virus (LCMV)
Pneumonia Virus of Mice (PVM)
Reovirus Type 3 (REO)
Sendai Virus (SenV)
Simian virus type 5 (SV5)
Sartorius recognizes the importance of sensitive and specific assays to detect virus contamination and has identified a number of viral risks for specific species types – human, simian, bovine, porcine, avian, rabbit and insect. Our scientists can develop specific tests to meet any custom assay requirements.
Assay Package | Viruses Detected |
|---|---|
Human | HIV types 1 and 2; HTLV types 1 and 2; hepatitis virus types A, B and C; human bocavirus, human herpes simplex virus types 1 and 2 human herpes virus types 6, 7 and 8; CMV; VZV; EBV; parvovirus B19;SRV-1 and 2; simian foamy virus; human papilloma types 16 and 18; human polyomavirus JC and BK; enterovirus, rubella, West Nile virus |
Simian | Simian virus 40, simian foamy virus, simian immunodeficiency virus, simian retrovirus, simian T cell lymphotropic virus |
Bovine | Blue tongue virus, bovine adenovirus, bovine adenovirus type 3, bovine parvovirus, bovine respiratory syncytial virus, bovine papillomavirus type 4, reovirus, rabies virus, bovine viral diahorrea virus, bovine polyoma virus, bovine circovirus, bovine parainfluenza virus type 3, bovine herpes virus type 1 |
Porcine | Porcine adenovirus, porcine parvovirus, TGV, hemagglutinating encephalomyelitis virus, porcine circovirus |
Avian | Avian leukosis virus type J, avian nephritis virus, avian rotavirus, reticuloendothelial virus, chicken anaemia virus, Newcastle disease virus |
Rabbit | Rabbit kidney vacuolating virus, rabbit hemorrhagic disease virus, Shope fibroma virus, rabbit oral papilloma virus, borna disease virus, adeno associated virus |
Insect | Boolarra virus, pariacato virus, flock house virus, nodamura virus |
Custom PCR Asssays
Sartorius experts have developed a PCR assay for the emerging virus SARS-CoV-2. This assay is fully validated, ready to use and can be integrated into a QC Testing plan to mitigate risk of contamination in cell banks, viral seed stocks and manufacturing processes and products.
Single target custom PCR assays can be developed and validated on request to meet your QC Testing strategy.
