Risk of TSE/BSE in Drug Manufacturing

In the pharmaceutical industry, the source of every raw material is critical to ensuring patient safety. When raw materials are derived from animal sources, a unique and severe risk emerges: Transmissible Spongiform Encephalopathy (TSE), commonly known in cattle as Bovine Spongiform Encephalopathy (BSE), or "mad cow disease."

TSEs are fatal, neurodegenerative disorders caused by infectious proteins called Prions. Because these prions are highly stable and resistant to typical sterilization methods, the global pharmaceutical supply chain must implement rigorous controls to prevent their transmission to humans via medicinal products.

What are TSE and BSE? The Prion Threat

TSEs are characterized by the porous (spongy) appearance they cause in the brain and spinal cord, easily visible under a microscope.

The Prion

Prions are unique infectious agents—highly stable proteins that are resistant to drying, freezing, and even standard cooking temperatures. They are not destroyed by routine sterilization processes, making them a major manufacturing challenge.

BSE ("Mad Cow Disease")

Target: Primarily affects cattle, sheep, and goats.
Incubation: Has a long incubation period (around five years in cattle).
Cause: The known cause of BSE transmission in cattle was protein cattle feed containing infected material (meat and bone meal), which the FDA banned in 1997.
Geography: While cases have been reported globally, the majority of historical cases originated in European countries, particularly the United Kingdom.

vCJD: The Human Form

BSE transmits from cattle to humans in the form of variant Creutzfeldt–Jakob Disease (vCJD), which is the most commonly known human TSE.

The Pathways of Transmission in Healthcare

While TSEs do not transmit through the air, they are highly contagious through direct contact with infected tissues. For the healthcare system, the risk pathways are critical:

Pharmaceutical Dosage Forms: Products like Gelatin (used in capsules) and other excipients derived from animal sources (bovine, ovine) can potentially carry the TSE infection.
Blood and Plasma Products: Blood and plasma can act as major vehicles for the transmission of this disease.
Medical & Surgical Instruments: Since prions resist normal sterilization, surgical instruments used on infected tissues can become a source of transmission.

🛡️ Global and Indian Regulatory Requirements

Because TSEs currently have no effective treatment, the global strategy is focused entirely on prevention and exclusion.

1. Sourcing and Certification

For pharmaceutical products using animal-derived materials, mandatory steps include:

TSE/BSE Certification: Manufacturers must obtain certification from suppliers confirming that the materials are free from TSE/BSE risk.
Source Verification: Materials must preferably be imported from countries designated as negligible risk by international health authorities.
ANDA Filing: Details regarding TSE and BSE risk assessment are a required component of ANDA (Abbreviated New Drug Application) filings submitted to the FDA.

2. Mandatory Verification of Animal-Origin Products

Complete verification of the raw material source is non-negotiable and must include data on:

Animal Type: (e.g., sheep, horse, cow, goat).
Tissue Type: The specific tissue or body part from which the product is derived (e.g., hide, bone).
Animal Health & Age: Health status and age of the source animal.
Geographical Location: Country of origin (confirming the area's risk status).
Risk Assessment: Evaluation of cross-contamination risk during handling and packing.

3. Indian Guidelines

The Central Drugs Standard Control Organization (CDSCO), under the Ministry of Health, Government of India, has published specific guidelines on TSE and BSE requirements, ensuring that domestic manufacturers and importers adhere to global risk-mitigation standards.

By diligently tracing the origin of every animal-derived component and demanding rigorous certification, the pharmaceutical industry acts as the first line of defense against the silent, persistent threat of Prion diseases.