TSE/BSE Evaluation

TSE/BSE is a type of disease affected to the animals which may transmit to the humans if any products obtained by the disease caused animal may affect to humans also
The many biologic products are expracted from the animal source so before the extraction the animal should be tested for TSE/BSE organism in their source/Body

1. TSE/BSE EVALUATION PRESENTED BY: Sridhar S Pharmaceutical regulatory affairs JSSCP, M ysuru PRESENTED TO: Dr. Balamuralidara V Asst. Professor Dept. of Pharmaceutics JSSCP, Mysuru

2. What is TSE TSE – Transmissible Spongiform Encephalopathy – In general, it is a disease. A group of rare degenerative brain disorders characterized by tiny holes that give the brain a " spongy " appearance. It is a rare disease occurs in Humans and Vertebrate animals (Vertebrate = Animals having backbone ) TSE = A disease capable of being transmitted by infection and gives the appearance of sponge like tiny holes in the brain. There are many types of Human TSEs . The literal meaning of TSE is as below Transmissible = Capable of being transmitted by infection Spongiform = Sponge like Encephalopathy = Brain Disease

3. What is BSE BSE – Bovine Spongiform Encephalopathy – It is a brain disease that occurs in bovines; generally known as “Mad Cow Disease ” It is a rare disease occurs in Vertebrate animals; for example, cow/cattle . BSE = A disease capable of transmitted by infection and gives a appearance of sponge like tiny holes in the brain of bovines . The literal meaning of BSE is as below Bovine = Characteristic of or resembling cows or cattle . Spongiform = Sponge like Encephalopathy = Brain Disease

4. Causative Agent The causative agent is NOT a bacterium or a virus or a fungus or any plant(s). It is a protein called as Prion, usually present in the body cells of Human and Animals. The structure of the prion protein is given below

5. Prion have two forms as said below. Prion = proteinaceous infectious particle, named as Prion Proteins Normal Form-A harmless protein found in the body's cells which is unfolded in structure which does not cause TSE Abnormal Form-The protein which is in folded structure and can cause TSE Both normal and abnormal prion are identical except the folding in the structure of abnormal proteins. The accumulation of an abnormal isoform of the prion protein in the Central Nervous System causes the diseases. Creutzfeldt-Jakob disease in its sporadic form is the most frequent type of human TSE After the name of the causative agent the disease is also named as prion diseases.

6. DEVELOPMENT OF TSE/BSE Spontaneous development of folded protein in sheep/goat (by mutation) Consumption of meat powder by cattle/Bovine to increase the milk productivity Use of animal derived products in pharmaceuticals Use of animal derived products in pharmaceuticals Development of TSE in Human

7. RISK of TSE/BSE in Pharmaceuticals There is a possible risk of contamination of infected animal derived products in the pharmaceutical finished dosage form for human consumption leads to transmission of TSE/BSE to human beings. In some cases, the Pharmaceutical preparations like Finished Dosage Forms, Active Pharmaceutical Ingredients and their Starting Materials, and Primary Packaging Materials involves the use of products/materials derived from animals. For example, use of proteins, enzymes, amino acids from animals used in the manufacturing of API and API starting materials. The primary packaging materials like gelatins capsules derived from the fat of animals also increases the possibilities of transmission of TSE/BSE.

8. There is a high risk in the case of biotechnological products like serums, blood products and vaccines where the source material is derived from animals and animal derived products. There is also a possible risk of TSE/BSE through the equipments/utilities where in biologically-derived products and/or products of animal origin is handled. For example, Culture media used in reactors for media fill studies. Ideally, the use of such animal derived product/material should be avoided in the pharmaceutical preparation. However, during unavoidable circumstances, the use of such animal derived products is accepted, provided that the manufacturing process and procedures complies to the applicable regulations set by WHO, European Commission and USFDA.

9. Regulation Regulation (EC) No 999/2001 of the European Parliament and of the Council of 22 May 2001 laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies   The following guidance and regulatory compliance activities are available at present: WHO Fact Sheet & Guidelines USFDA guidelines EU Guidelines General Monograph in European Pharmacopeia Certificate of Suitability for TSE/BSE by EDQM Canadian Guidelines http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:02001R0999-20150805

10. Inspections, Controls & Registration The Directorate General for Health and Food Safety of the European Commission carries out audits in the Member States to verify the correct implementation, enforcement and control of EU legislation by the competent national authorities TSEs are laid down in Annex IX to the TSE Regulation, status of third countries or regions thereof, as laid down in Commission Decision 2007/453/EC.

11. Reference http://ec.europa.eu/food/safety/biosafety/food_borne_diseases/tse_bse_en http://www.insightcgmp.com/wp-content/uploads/2015/11/tse-bse-risk-regulations.pdf http://eur-lex.europa.eu/legalcontent/EN/TXT/?uri=CELEX:02001R0999-20150805 http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000096.jsp&mid=WC0b01ac05800265d1 http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000138.jsp&mid=WC0b01ac05800265d2 http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000533.jsp&mid=WC0b01ac05805716fa http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000137.jsp&mid=WC0b01ac05800267b7

12. Any Question???????