Certain medical devices utilize animal materials in their manufacture to provide performance characteristics that are more advantageous than non-animal-based materials.
The use of animal material, however, carries the risk of transmitting infectious diseases when it is improperly collected, stored or processed (e.g. prion diseases). Transmissible Spongiform Encephalopathy (TSE) is a prion disease that can affect the brain and nervous system of many animals including bovine, ovine, caprine, deer, elk, and mink. Outbreaks of Bovine Spongiform Encephalopathy (BSE) i.e., “mad cow disease” are the reason for the strict control of the use of animal material in medical devices as if it is passed onto humans, can cause brain infection and be fatal.
Currently, there are no treatments for TSE diseases and no validated screening tests that detect infection in a live animal or human (https://www.fda.gov/media/87251/download) therefore the risks of transmitting infectious disease through animal tissue must be strictly controlled through the selection of source material demonstrating the ability to remove or inactivate contamination of transmissible agents.
Examples of medical devices containing animal material include:
- Bovine/ porcine heart valves
- Bone substitutes for use in dental applications
- Collagen injections
- Gelatin-sealed grafts
FDA guidance for Medical Devices Containing Materials Derived from Animal Sources
In March 2019, the FDA issued their updated guidance on the use of medical devices containing materials derived from animal sources (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-devices-containing-materials-derived-animal-sources-except-in-vitro-diagnostic-devices
The guidance is intended to help medical device companies establish and document procedures to mitigate the risk of infectious disease exposure through contact with devices containing animal-derived materials. The guidance includes controls for animal tissue collection, manufacturing controls for animal tissue components, sterilisation and TSE-specific issues and what information to include in the Device History File (DHF).
What information must be documented by the manufacturer and included in the Device History Record?
Following the FDA guidance, the manufacturer must include the following in the device history record (DHR):
- animal species used
- age of animal at slaughter
- specific tissue(s) used
- animal’s country of origin and country of residence
- status of the herd or collection of organisms (e.g., closed herd/ group)
- methods for actively monitoring the health of the herd and the health of specific animals from which tissues are collected (e.g., vaccinations with live modified viruses that can co-purify in the desired tissues, active surveillance for human pathogens)
- methods and conditions for transporting animal tissue (e.g., tissue refrigeration and quarantine)
- long-term health of the herd (breeding history, vaccinations, inspections)
- USDA status of the abattoir
- tests performed (and release criteria) for permitting tissue to be further processed and/or combined with other tissues and device components (e.g. Certificate of Analysis).
- Material Safety Data Sheets
- quarantine procedures
- test methods and acceptance criteria for assessing in-process and final product bioburden or sterility
- methods for facility decontamination/ sterilisation so that cross-contamination is avoided
ISO 22442 Medical device utilising animal tissues and their derivatives
The FDA guidance aligns with and provides further clarification on the use of the ISO 22442 series of standards “Medical device utilising animal tissues and their derivatives”. This series of ISO standards includes:
- ISO 22442-2, “Medical devices utilizing animal tissues and their derivatives – Part 2: Controls on sourcing, collection and handling,” (Note: Refer to ISO 13485 “Medical devices – Quality management systems – requirements for regulatory purposes”. The quality management system elements that are required by this document can form a part of a quality management system conforming to ISO 13485)
- ISO 22442-3 “Medical devices utilizing animal tissues and their derivatives – Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents.
ISO 22442‑1 is intended to provide requirements and guidance on risk management related to the hazards typical of medical devices manufactured utilizing animal tissues or derivatives such as:
- contamination by bacteria, moulds or yeasts
- contamination by viruses
- contamination by agents causing transmissible spongiform encephalopathies (TSE)
- material responsible for undesired pyrogenic, immunological or toxicological reactions.
ISO 22442‑2 is intended to provide requirements and guidance on:
- quality system elements
- personnel and training
- sourcing, collection, handling, storage, transport and labelling of animals and tissues
ISO 22442‑3 is intended to provide requirements and guidance on:
- validation of the elimination and/or inactivation of viruses and TSE agents during manufacturing
- literature review
- elimination and/or inactivation study of viruses and TSE agents
- routine monitoring and control of critical process parameters.
At PharmOut, our consultants have assisted several medical device clients to audit their suppliers of materials of animal origin to ISO 22442 and ISO 13485.
Please contact PharmOut to enquire about our auditing services. We can facilitate both on-site and remote auditing, as well as provide recommendations and guidance on addressing and resolving your audit deficiencies.
Looking to learn more? Take a look at the Online GMP Training eLearning course for ISO 22442-2 Medical Devices Utilising Animal Tissues or Derivatives.