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Medical Devices Containing Materials Derived 

from Animal Sources (Except For In Vitro

Diagnostic Devices)

Anjana Jain

Biomedical Engineer

Division of Surgical Devices/ Office of Device Evaluation 

and

Scott McNamee

Materials Engineer

Office of Compliance

April 23, 2019
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• Objectives 

• Background

• Scope of the guidance document

• Topics covered in the guidance document

• How this affects stakeholders

Agenda
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Objectives

• Become familiar with the content of the revised final guidance 

document issued on March 15, 2019.

• Understand the difference between the previous final guidance 

document issued in 1998 and the revised final guidance document. 

• Identify resources available to aid in preparation of submissions of 

medical devices with animal-derived materials.
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• The previous final guidance document on this topic was published in 1998 and 

addressed ways to specifically reduce the potential of exposure to bovine 

spongiform encephalopathy (BSE). 

• The draft guidance for the revised final guidance document (“Medical Devices 

Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic 

Devices)”) was issued on January 23, 2014.

– The draft guidance was revised to provide clarity on the following areas:

1. The intersection between the standards and the guidance document;

2. The information that should be documented in a premarket submission 

versus manufacturing facility records; and

3. How to apply the Quality System Regulation.

– Additionally, the specific benchmark for the sponsor to demonstrate a 

reduction of 6 logs of the viral load was removed. Now we recommend 

demonstrating that the sum of the log reduction is sufficient to produce a safe 

product.

Background
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• The revised final guidance document (2019) is different from the existing 

guidance document (1998) as it:

1. Provides recommendations related to viral pathogens and all transmissible 

spongiform encephalopathies (TSEs) not just bovine spongiform 

encephalopathy (BSE).

2. Outlines information regarding animal sourcing and manufacturing that 

should be provided in premarket submissions and/or documented to file.

3. Recommends how viral inactivation studies should demonstrate that the 

sum of the log reduction in virus of select processing steps and sterilization 

process(es) is sufficient to produce a safe product.

Background
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• Animal: any vertebrate or invertebrate (including amphibian, anthropod [for 

example crustacean], bird, coral, fish, reptile, mollusk and mammal) excluding 

humans (homo sapiens)

• Ruminant: an even-toed ungulate mammal that chews the cud regurgitated 

from its rumen

• Transmissible agents: bacteria, mold, yeast, parasites, viruses, transmissible 

spongiform encephalopathies (TSEs) agents and unclassified pathogenic 

entities

• Inactivation: process by which the ability to cause infection or pathogenic 

reaction by a transmissible agent is reduced

• Non-viable: having no potential for metabolism or multiplication

Definitions

Please note that definitions are from standard ISO 22442-1
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The information in the guidance is applicable to all medical devices, except in vitro 

diagnostic devices and devices with animal materials generally recognized as safe (e.g., 

tallow derivatives), that contain or are exposed to animal-derived materials.

The guidance provides:

1. Information that the FDA believes is important to document the safe and

consistent manufacture of medical devices containing animal tissue;

2. Information that should be included in a premarket submission for products

within the scope of the guidance;

3. Recommendations about how specific areas of Quality System Regulation

should be applied to control and document the safe and consistent manufacture

of medical devices containing animal tissue; and

4. More information on specific approaches for determining the ability of 

manufacturing methods to eliminate viral contamination in the final product. 

Scope
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• International Standard ISO 22442 series, “Medical devices utilizing animal tissues and 

their derivatives – Part 1: Application of risk management,” “Part 2: Controls on 

sourcing, collection and handling,” and “Part 3: Validation of the elimination and/or 

inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents” 

provide recommendations for selection and handling of animal tissues as well as 

evaluating the risk of pathogen contamination in medical devices.

• FDA partially recognizes Part 1. Specifically, Clause 4.4.2 is not recognized 

– Clause states that if manufacturers cannot fully meet the requirements of ISO 

22442-2, they may demonstrate the level of inactivation of transmissible agents 

(per ISO 22442-3) is sufficient.

– FDA’s position is that the specifications outlined in both ISO 22442-2 and ISO 

22442-3 should be met.

• FDA fully recognizes Part 2 and Part 3.

Standard ISO 22442
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• The guidance document communicates the following recommendations for how 

the manufacturer should control animal tissue collection:

1. Document the sourcing and handling of animal tissues, and 

2. Understand the capabilities of the manufacturing and sterilization processes 

to address the risks to patients.

• Premarket submission should include the following:

1. Animal sourcing information that is consistent with standard ISO 22442-2,

2. Tests performed for permitting tissue to be further processed and/or 

combined with other tissues and device components, and 

3. Material Safety Data Sheets.

Control of Animal Tissue Collection
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In accordance with the Quality System Regulation, the manufacturing facility 

should document:

1. Procedures for maintaining records on the animal sourcing, 

2. The information on animal sourcing provided for each lot of product 

manufactured, and

3. Methods for facility decontamination/sterilization to avoid crosscontamination.

Manufacturing Controls for Animal Tissue Components
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• The validation of sterilization of devices containing animal tissue is complex and 

requires a case-by-case assessment.

• The guidance document references a series of standards (ISO 11135, ISO 

17665, ISO 11137-1, ISO 11737-1 and -2, etc.).

• Other resources may include: 

1. For 510(k) submissions, please also refer to the guidance document 

“Submission and Review of Sterility Information in Premarket Notification 

(510(k)) Submissions for Devices Labeled as Sterile.”

2. For Premarket Approvals and De Novos, the general review process should 

be followed.

Sterilization
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• To ensure adequate inactivation and removal of viruses, the processing 

methods and sterilization techniques used in product manufacture should be 

assessed.

• Consistent with standard ISO 22442-3, the sponsor may either provide test 

reports for each manufacturing step that contributes to the reduction in the viral 

load or provide literature-based evidence for each manufacturing step.

• When a sponsor conducts testing to demonstrate viral inactivation of the 

medical device, the model viruses should be selected to reflect the actual viral 

contaminants that may be present in the source animal tissue (for example, 

DNA-based and RNA-based enveloped and non-enveloped viruses).

Validation of Viral Inactivation
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• The results of viral inactivation studies should demonstrate that the sum of the 

log reduction in virus of select processing steps and sterilization process(es) is 

sufficient to produce a safe product.

• A final report should be included in the premarket submission with the following 

information:

1. Animal species and tissue source material in the device as well as amount 

of virus(es) that might be present in the source material,

2. Appropriateness of the model viruses selected,

3. Relevance of conditions used in the virus inactivation studies to the 

commercial manufacturing methods, and 

4. Why these studies demonstrate that the final product will be safe.

Validation of Viral Inactivation
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• There is no treatment for transmissible spongiform encephalopathy (TSE) diseases 

and no validation screening tests that detect infection in a live animal or human. 

Diagnosis is confirmed during post-mortem microscopic examination of brain tissue.

• The premarket submission for any material derived from ruminant animals should 

include the following:

1. Whether the animals were sourced from a country or countries with negligible, 

controlled or unknown bovine spongiform encephalopathy (BSE) risk,

2. Information on the long-term health of the herd,

3. Animal feed composition,

4. Animal stunning and slaughter methods that reduce the risk of cross contaminating 

non-TSE tissues with materials from tissues that may contain TSE, and 

5. Information about ante-mortem and post-mortem inspections.

Transmissible Spongiform Encephalopathy (TSE)
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• The guidance document will provide more clarity to the stakeholders 

in understanding what information should be submitted in premarket 

submissions related to medical devices with animal-derived 

materials, as well as what information should be documented in the 

manufacturing records.

• The guidance document helps manufacturers identify and manage 

the possible risks related to tissues from animal sources when these 

tissues are used in medical devices.

Summary
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• The revised final guidance document may be found using this 

link:

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuid

ance/GuidanceDocuments/UCM381491

• Standard ISO 22442 - Parts 1, 2, and 3

• ICH “Viral Safety Evaluation of Biotechnology Products Derived 

from Cell Lines of Human or Animal Origin Q5a(R1)”

Resources
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Questions?

Division of Industry and Consumer Education: 

DICE@fda.hhs.gov

Slide Presentation, Transcript and Webinar 

Recording will be available at:

http://www.fda.gov/training/cdrhlearn

Under Heading: Specialty Technical Topics; 

Sub-heading: Animal Related Policy