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, Mysuru
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/genera
l_content_000096.jsp&mid=WC0b01ac05800265d1
 http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listi
ng/document_listing_000138.jsp&mid=WC0b01ac05800265d2
 http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/genera
l_content_000533.jsp&mid=WC0b01ac05805716fa
 http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listi
ng/document_listing_000137.jsp&mid=WC0b01ac05800267b7

12. Any Question???????