What is Transmissible Spongiform Encephalopathy (TSE) / Bovine Spongiform Encephalopathy (BSE). How to minimize the risk of TSE/BSE in pharmaceuticals. A number of cases found in the previous few years.
Active pharmaceutical ingredients (APIs), excipients, etc. play a most important role as a raw material in the manufacturing of dosage form. These Active pharmaceutical ingredients (APIs), excipients are prepared by a chemical Synthesis, fermentation, the extraction process, etc.
Some of the active pharmaceutical ingredients, excipients, and dosage form manufacturing process contains animal species material. Most of the dairy, food , biological manufacturing industry used animal species material and the pharmaceutical industry used extracted material like casein, lactose, etc for the manufacturing of the dosage form.
For vendor qualification, pharmaceutical industries required Transmissible Spongiform Encephalopathy (TSE) / Bovine Spongiform Encephalopathy (BSE) the certificate indicates that products of the vendor comply with the guideline or the regulatory requirements.
1.0 What is Transmissible Spongiform Encephalopathy / Bovine Spongiform Encephalopathy and its Origin/History:
1.1 Transmissible Spongiform Encephalopathies are a chronic degenerative nervous disease. The reason for TSE is the growth of PrP or prion protein.
1.2 Prion protein is an abnormal isoform of a cellular glycoprotein. This prion protein/PrP is the infective agent responsible for transmitting Transmissible Spongiform Encephalopathy disease.
|Type of Transmissible Spongiform Encephalopathy (TSE)|
1.3 Prion protein may survive in high as well as freezing temperatures. In this disease brain form sponge-like nature and lesion on the brain.
1.4 Bovine Spongiform Encephalopathy (BSE) is a type of Transmissible Spongiform Encephalopathies disease.
1.5 Bovine Spongiform Encephalopathy (BSE) disease found in the cow (cattle).
1.6 Bovine Spongiform Encephalopathy (BSE) is also popularly known as Mad cow disease.
1.7 The first case of BSE was identified in the United Kingdom (1986). A large number of cows and people have been affected due to Bovine Spongiform Encephalopathy (BSE).
2.0 Type of Transmissible Spongiform Encephalopathy (TSE):
BSE is a type of TSE.
2.1 Cow / cattle – Bovine Spongiform Encephalopathy (BSE)
2.2 Sheep and goats – scrapie disease
2.3 Deer – chronic wasting disease (CWD)
2.4 Mink – transmissible mink encephalopathy (TME)
2.5 Cats – feline spongiform encephalopathy (FSE)
2.6 Zoos – spongiform encephalopathy of exotic ungulates
3.0 Transmission of Transmissible Spongiform Encephalopathy / Bovine Spongiform Encephalopathy:
3.1 It is occurred after eating meat or bone meal from TSE infected animals. Human disease caused by eating the meat of the bovine spongiform encephalopathy (BSE) an infected animal called Variant Creutzfeldt-Jakob Disease (vCJD).
Source of human-to-human transmission has three main factors:
1) an unknown number of people infected with the BSE agent
2) the prion protein is present in some of the patients who died of vCJD
3) blood of infected animals with TSE agents has transmitted the disease experimentally.
3.2 To avoid the spread of vCJD disease worldwide, the manufacturing unit of vaccines, blood products, and other pharmaceutical products that do not contain bovine-derived or human (infected) derived materials.
3.3 The regulatory authorities have available enough and reliable data to evaluate the risk and safety of the product, so that regulatory authorities have taken steps to prevent the transmission of TSE to humans via pharmaceutical products.
4.0 How to minimize the risk of Transmissible Spongiform Encephalopathy / Bovine Spongiform Encephalopathy?
4.1 Manufacturer choice:
If manufacture have a choice to use the materials from ‘non-TSE-relevant origin’ (chemical origin) then preferred the non-TSE-relevant origin (chemical origin) material for the manufacturing of the product. If the manufacture has no choice, in such case justification is given why ‘TSE- relevant animal species’ material is using instead of materials from ‘non-TSE- relevant species’ (chemical origin). If ‘TSE-relevant animal species’ materials used, then all the necessary precautions to minimize the risk of transmission of TSE considered.
4.2 Source of animal
Material derived from an animal should be good for human consumption. Hence. The selection of healthy animals is very important. A medical examination is performed on animals prior to use. The age of animals also consider while choosing animals as source.
4.3 Geographical region
Bovine material Countries divide into 3 parts choose the country appropriately for the manufacturer so lower the risk of Transmissible Spongiform Encephalopathy / Bovine Spongiform Encephalopathy:
- Negligible BSE risk countries – The lowest possibility of TSE spread, safe animal source
- Controlled BSE risk countries – Moderate possibility of TSE spread
- Undetermined BSE risk countries – The highest possibility of TSE spread. Required justification for using the material.
4.4 Animal part, Tissues, and fluid
As per based on the risk of disease animal parts, tissues, fluid are divided into 3 parts:
Selection of animal parts, tissues, fluid as per the below category help to minimize risk of TSE, BSE.
Tissue / Fluid / parts
A – High Infectivity central Nervous Tissue
Brain, skull, spinal cord, the optic nerve, Pituitary Gland, dura mater Alimentary Tract: Small Intestine including intestinal mucosa. Lymphoreticular Tissues: Tonsils
B – Lower Infectivity peripheral Tissues
Spleen, Lymph nodes, the large intestine, Cerebrospinal Fluid, Blood, Lungs, Liver, Kidney, Adrenal, Pancreas, Bone Marrow, Blood Vessels, Olfactory Mucosa, Gingival Tissue, Salivary Gland, Cornea
C – Tissues with No Detected Infectivity
Milk, Colostrum, Cord Blood, Saliva, Sweat, Tears, Nasal Mucous, Urine, Feces Testes, Prostate/Epididymus/Seminal Vesicle, Semen, Ovary, Uterus, Placenta Fluids, Fetus, Embryos, Skeletal Muscle, Tongue, Heart
4.5 Risk Assessment
Risk Assessment is the best tool means to identify the presence of prion protein is minimized or not. The action taken to deal with the risk of TSEs through medicinal products indicates risk minimization rather than risk elimination. Compliance with regulatory bodies should be based on a risk assessment.
4.6 Tissue removal
Infectious tissues are removed from animal parts by certain procedures. The procedure of removal of tissue should be validated.
5.1 Transmissible Spongiform Encephalopathies in relation to Biological and pharmaceutical Products WHO Guidelines
5.2 Notices From European Union Institutions, Bodies, Offices And Agencies European Commission (Ema/410/01 Rev.3)
1. What is the difference between TSE and BSE?
Transmissible Spongiform Encephalopathies (TSE) is a chronic degenerative nervous disease. The growth of PrP or prion protein is responsible for TSE. Prion protein is an abnormal isoform of a cellular glycoprotein. Bovine Spongiform Encephalopathy (BSE) is a type of Transmissible Spongiform Encephalopathies disease. Bovine Spongiform Encephalopathy (BSE) disease is found in the cow (cattle). Bovine Spongiform Encephalopathy (BSE) is also popularly known as Mad cow disease.
2. What is BSE and TSE certificate?
For vendor qualification, TSE/BSE certificate is required. Material is should be free from TSE/BSE or comply with the guideline of TSE / BSE. CEP (Certificate of suitability) certificate provides the assurance that the material complies with the European Directorate acceptance criteria.
At least, below document required related to TSE/BSE for vendor or material acceptance:
1. CEP certificate – Necessary, If animal-based raw material is used for the product manufacturing
2. TSE/BSE free declaration from the manufacturer/vendor – Provide if the manufacturing process does not contain any animal-based raw naterial.
3. What are the types of TSE?
Transmissible Spongiform Encephalopathies are chronic degenerative nervous diseases. The reason for TSE is the growth of PrP or prion protein.
The difference between TSE and BSE – BSE is a type of TSE.
Types of TSE –
1. Cow/cattle – Bovine Spongiform Encephalopathy (BSE)
2. Sheep and goats – scrapie disease
3. Deer – chronic wasting disease (CWD)
4. Mink – transmissible mink encephalopathy (TME)
5. Cats – feline spongiform encephalopathy (FSE)
6. Zoos – spongiform encephalopathy of exotic ungulates
4. What is a BSE/TSE certificate and why should you care?
TSE (Transmissible Spongiform Encephalopathy) and BSE (Bovin Spongiform Encephalopathy) is a disease caused by prion protein. Bovine Spongiform Encephalopathy (BSE) is also popularly known as Mad cow disease. TSE/BSE certificate is a CEP (Certificate of suitability) certificate that provides assurance that material or product is free from TSE/BSE. Ultimately, customer trust in our product increases the sales of a product.