Contains Nonbinding Recommendations 
 
Medical Devices Containing Materials 
Derived from Animal Sources (Except 
for In Vitro Diagnostic Devices) 
Guidance for Industry and 
Food and Drug Administration Staff 
 
 
 
Document issued on March 15, 2019.  
The draft of this document was issued on January 23, 2014. 
 
This document supersedes Medical Devices Containing Materials Derived 
from Animal Sources (Except for In Vitro Diagnostic Devices) issued 
November 6, 1998. 
For questions about this document contact Division of Surgical Devices at (301) 796-6970. 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
 
    Contains Nonbinding Recommendations 
 
 
 
Preface 
 
 
Public Comment 
You may submit electronic comments and suggestions at any time for Agency consideration 
to https://www.regulations.gov. Submit written comments to the Dockets Management Staff, 
Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 
20852. Identify all comments with the docket number FDA-2013-D-1574. Comments may 
not be acted upon by the Agency until the document is next revised or updated. 
 
Additional Copies 
Additional copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance.  Please use the document 
number 2206 to identify the guidance you are requesting.    Contains Nonbinding Recommendations 
 
Table of Contents 
I.  Introduction........................................................................................................................................1
II.  Background........................................................................................................................................2
III.  Scope ..................................................................................................................................................3
IV.  Considerations When Using Animal-Derived Materials...................................................................4
A.  Control of Animal Tissue Collection ..............................................................................................4
B.  Manufacturing Controls for Animal Tissue Components ..............................................................5
C.  Sterilization....................................................................................................................................6
D.  Transmissible Spongiform Encephalopathy-Specific Issues .........................................................8   Contains Nonbinding Recommendations 
Medical Devices Containing Materials 
Derived from Animal Sources (Except 
for In Vitro Diagnostic Devices) 
Guidance for Industry and  
Food and Drug Administration Staff  
This guidance represents the current thinking of the Food and Drug Administration (FDA 
or Agency) on this topic.  It does not establish any rights for any person and is not binding 
on FDA or the public.  You can use an alternative approach if it satisfies the requirements of 
the applicable statutes and regulations.  To discuss an alternative approach, contact the FDA 
staff or Office responsible for this guidance as listed on the title page.  
I.  Introduction 
The Food and Drug Administration (FDA) is issuing this guidance to update the policy 
regarding the use of animal-derived material in medical device manufacturing.  The role of 
animal-derived material in medical devices is well established.  However, these materials may 
carry a risk of transmitting infectious disease when improperly collected, stored, or 
manufactured.  The purpose of this guidance is to provide further clarification and updated 
information on the use of International Organization for Standardization (ISO) 22442-1 
Medical devices utilizing animal tissues and their derivatives  Part 1: Application of risk 
management, ISO 22442-2, Medical devices utilizing animal tissues and their derivatives  
Part 2: Controls on sourcing, collection and handling, and 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 to support 
applications to FDA.  This guidance also provides recommendations regarding methods for 
controlling the sourcing of animal tissues with regard to viral pathogens and evaluating the 
ability of manufacturing methods to remove such pathogens from the final product. This 
guidance replaces Medical Devices Containing Materials Derived from Animal Sources 
(Except for In Vitro Diagnostic Devices) issued November 6, 1998 (the 1998 guidance.)  
For the current edition of the FDA-recognized standard(s) referenced in this document, see the 
FDA Recognized Consensus Standards Database.1   
                                                            
1 Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm  
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    Contains Nonbinding Recommendations 
Throughout this guidance document, the term we refers to FDA staff from CDRH. You 
and your refers to the manufacturer. 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited.  The use of the word should in Agency guidance means that something 
is suggested or recommended, but not required. 
II.  Background
 
This guidance updates the 1998 guidance by addressing aspects of potential risk from the use of 
animal tissues and now includes recommendations related to viral pathogens and all 
transmissible spongiform encephalopathies (TSEs).  The 1998 guidance addressed ways to 
reduce the potential for exposure to one specific TSE, bovine spongiform encephalopathy 
(BSE).  This document continues to focus on the control of transmissible disease, and contains 
recommendations for documenting the source of animal tissue and conducting viral inactivation 
validation studies.  Commercial production of animals as sources of bodily tissues used in 
medical devices can introduce several kinds of risks.  The 1998 document primarily addressed 
geographical factors in the sourcing of the animal tissue.  In addition to geographical factors, 
this document includes recommendations that recognize the role of appropriate animal 
husbandry to ensure safe tissue sources. 
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, provides recommendations for 
selection and handling of animal tissues as well as evaluating the risk of pathogen 
contamination in medical devices.  Used in concert with the ISO 22442 series of standards, this 
guidance is intended to help you identify the possible risks related to medical device 
components and/or manufacturing reagents that are sourced from animal tissues.   
We also recognize that an ISO standard is a document that undergoes periodic review and is 
subject to revision.  Through the FDA standards recognition process, CDRH provides 
information regarding the extent of recognition of the ISO 22442 series of standards through 
Supplementary Information Sheets published on the FDA website.2  FDA will make updates to 
this guidance document as appropriate, should future revisions to the ISO 22442 series of 
standards result in significant changes to the recommendations in this document. 
                                                            
2 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm 
2 
    Contains Nonbinding Recommendations 
III.  Scope 
The information in this guidance is applicable to all medical devices that contain or are exposed 
(e.g., through a manufacturing reagent) to animal-derived (e.g., bovine, ovine, porcine, avian) 
materials with the exception of in vitro diagnostic devices and materials generally recognized to 
be safe based on their method of manufacture (e.g., tallow derivatives as described in Annex C 
of ISO 22442-1: 2015).  This guidance addresses the risks of human pathogens that could 
contaminate animal material and be present in a medical device.  For devices that indirectly 
contact humans, this guidance considers the risk to patients (e.g., how might indirect contact 
result in pathogen exposure) and the healthcare provider who may handle device components 
that do not contact a patient.   
This guidance provides: 1) information that 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 this guidance; 
3) recommendations regarding how specific aspects of the Quality System (QS) Regulation3 
should be applied to control and document the safe and consistent manufacture of medical 
devices containing animal tissue; and 4) additional information on specific approaches for 
determining the ability of manufacturing methods to eliminate viral contamination in the final 
product.  In general, premarket submissions should include information on the specifics 
identified below or the methods by which the risks are mitigated.  In addition, records at the 
manufacturing facility should continue to document this information on each lot of product 
manufactured consistent with the QS Regulation. 
FDA has developed this guidance document to assist industry in preparing Premarket Approval 
(PMA) applications, Humanitarian Device Exemption (HDE) applications, Investigational 
Device Exemption (IDE) applications, Premarket Notification (510(k)) submissions, and De 
Novo requests for medical devices that contain device components derived from animal sources 
and come into direct or indirect contact with the human body.  This guidance is not applicable 
to medical devices that are derived from human tissues because the potential contaminants 
associated with human donor tissues are considerably different than those that are found in 
animal tissues. 
Should a manufacturer have questions about the applicability of this guidance to their specific 
product, we recommend consultation with FDA. 
 
 
                                                            
3 21 CFR part 820 
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    Contains Nonbinding Recommendations 
IV.  Considerations When Using AnimalDerived Materials
 
A.  Control of Animal Tissue Collection 
To ensure the safety of medical devices containing or contacting animal tissue, FDA believes 
that it is important: 1) to document the sourcing and handling of animal tissues as well as 2) to 
understand the capabilities of the manufacturing and sterilization processes to eliminate human 
pathogens.  Consequently, FDA recommends that you collect and document the information 
outlined below for animal tissue-derived materials that are used as either device components 
(e.g., pericardium, viscera, bone, hyaluronic acid, collagen) or manufacturing reagents (e.g., 
tissue culture media, enzymes).  For devices prepared from animal tissues that have a reduced 
risk of human pathogen contamination (e.g., crustaceans), FDA recommends that you address 
the information outlined below if applicable to that particular source material.  If determined 
not to be applicable, FDA recommends providing a scientific explanation (i.e., based on 
published literature or information from a recognized source (e.g., WHO, CDC, USDA)) that 
identifies the human pathogens that may be present in the animal species, and how your 
approach ensures device safety.   
Premarket submissions should include information on the items identified below, consistent 
with ISO 22442-2 and the methods by which the risks are mitigated4 if applicable.  You may 
document this information in a premarket submission or by reference to other regulatory 
submissions (e.g., Master File, PMA, 510(k)).   
  the animal species; 
  the age of the animal at slaughter; 
  the specific tissue(s) used (if multiple tissues are used, please identify all such tissues); 
  the animals country of origin and residence (with more specific geographic information 
when appropriate) when such information is available; 
  the status of the herd or collection of organisms (e.g., closed herd/group); 
  the 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 tissue, active surveillance for human pathogens); 
  the methods and conditions for transporting animal tissue (e.g., tissue refrigeration and 
quarantine);  
  the United States Department of Agriculture (USDA) status of the abattoir;5 
  the tests performed (and release criteria) for permitting tissue to be further processed 
and/or combined with other tissues and device components (e.g., a Certificate of 
Analysis); and 
  Material Safety Data Sheets may be helpful information to include in a regulatory 
submission, when available, because they provide an overview of the safety and 
                                                            
4 ISO 22442-1, Medical devices utilizing animal tissues and their derivatives  Part 1: Application of risk 
management 
5 USDA status is not included in ISO 22442-2, however, will provide additional assurance regarding the safety of 
the tissue used. 
4 
    Contains Nonbinding Recommendations 
potential toxicities related to that component, including information on any reagents 
used in the processing of the tissue, to support biocompatibility assessments.   
Certification of compliance with USDA Animal and Plant Health Inspection Service (APHIS) 
importation and/or USDA Food Safety and Inspection Service (FSIS) inspection requirements 
may be provided in lieu of any aforementioned items provided in these forms.   
In addition, the manufacturing facility should document 1) procedures for maintaining records 
on the above cited items6 and 2) all information outlined above on each lot of product 
manufactured (Device History Record).7  If necessary to ensure the safety of the medical device, 
this information may be reviewed during inspection.   
B.  Manufacturing Controls for Animal Tissue Components 
FDA also recommends that you collect and document the information listed below for each 
animal-derived material (and facility) used in device manufacture.  Premarket submissions 
should include information on the items identified below and the methods by which the risks 
are mitigated8 if applicable.  You may document this information in a premarket submission or 
by reference to other regulatory submissions (e.g., Master File, PMA, 510(k)).  The recommended 
information is: 
  test methods and release criteria permitting animal tissues to be further processed and/or 
combined with other animal tissue(s) or device components for manufacture; 
  quarantine procedures for tissues until they have met/failed release criteria; 
  test methods and acceptance criteria for assessing in-process and final product bioburden 
or sterility; and 
  methods for facility decontamination/sterilization so that cross-contamination is avoided. 
In addition, the manufacturing facility should document: 1) procedures for maintaining records 
on the above cited items;9 2) all information outlined above on each lot of product 
manufactured (Device History Record);10 and 3) information to validate the effectiveness of 
manufacturing equipment cleaning, decontamination, and sterilization relative to the specific 
pathogen exposure.11  If necessary to ensure the safety of the medical device, this information 
may be reviewed during inspection.   
The QS Regulation includes requirements related to the methods used in and the facilities and 
controls used for designing, manufacturing, packaging, labeling, storing, installing, and 
                                                            
6 21 CFR 820.70 
7 21 CFR 820.184 
8 ISO 22442-1, Medical devices utilizing animal tissues and their derivatives  Part 1: Application of risk 
management 
9 21 CFR 820.70 
10 21 CFR 820.184 
11 21 CFR 820.75  
 
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    Contains Nonbinding Recommendations 
servicing of medical devices.  Purchasing Controls, under 21 CFR 820.50, require final device 
manufacturers to establish procedures that ensure all purchased or otherwise received products 
and services conform to specified requirements, including those materials derived from animal 
sources.  The controls applied to manufacturing materials are expected to be appropriate to the 
manufacturing material, the intended use, and the effect of the manufacturing materials on 
safety and effectiveness (61 FR 52602, 52624).  Further information on the QS Regulation for 
certain premarket applications can be found in Quality System Information for Certain 
Premarket Application Reviews; Guidance for Industry and FDA Staff.12 
C.  Sterilization 
Because the issues for validating the sterilization of devices containing animal tissue are 
sufficiently complex to require a case-by-case assessment, we recommend you review the 
following FDA-recognized consensus standards:  
  ISO 11135, Sterilization of health-care products  Ethylene oxide  
Requirements for the development, validation and routine control of a 
sterilization process for medical devices 
  ISO 17665-1, Sterilization of health care products  Moist heat  Part 1: 
Requirements for the development, validation and routine control of a 
sterilization process for medical devices 
  ISO 11137-1, Sterilization of health care products  Radiation  Part 1: 
Requirements for development, validation and routine control of a sterilization 
process for medical devices 
  ISO 11737-1, Sterilization of medical devices  Microbiological methods  Part 
1: Determination of a population of microorganisms on products 
  ISO 11737-2, Sterilization of medical devices  Microbiological methods  Part 
2: Tests of sterility performed in the definition, validation and maintenance of a 
sterilization process 
  ISO 14160, Sterilization of health care products  Liquid chemical sterilizing 
agents for single-use medical devices utilizing animal tissues and their 
derivatives  Requirements for characterization, development, validation and 
routine control of a sterilization process for medical devices 
  ISO 14937, Sterilization of health care products  General requirements for 
characterization of a sterilizing agent and the development, validation, and 
routine control of a sterilization process for medical devices 
In addition, we recommend you contact the FDA staff responsible for reviewing your specific 
type of device to discuss your sterilization procedures further, if needed.13 
                                                            
12 Available at 
https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm070899
.pdf 
13 Please refer to FDAs guidance, Requests for Feedback on Medical Device Submissions: The Pre-Submission 
Program and Meetings with Food and Drug Administration Staff, available at 
 
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    Contains Nonbinding Recommendations 
When a viral pathogen in an animal tissue is part of the risk to the public health for a medical 
device, we recommend that you consider the extent to which processing and sterilization can 
inactivate or remove the virus(es).  FDA recommendations for validating viral inactivation 
methods are described below. 
Virus Validation Studies 
You should assess the processing methods and sterilization techniques used in product 
manufacture for their ability to inactivate and remove viruses.  Viral inactivation data are 
usually determined by comparing an estimate of the amount of virus in the unprocessed source 
material with the magnitude of virus inactivation /clearance provided by manufacturing and 
sterilization processes.  As suggested in ISO 22442 Part 3 (Section 5), a review of the published 
literature should be performed to estimate the amount of virus in the unprocessed source 
material and to optimize the design of the viral inactivation/elimination study (e.g., selection of 
model viruses and processing steps to be evaluated).  Such studies are generally performed 
using a scaled down version of specific production and sterilization steps (e.g., acid extraction 
of collagen or dry heat sterilization) with appropriate model viruses.  The model viruses used in 
these studies should be selected to reflect the actual viral contaminants that may be present in 
the source animal tissue (e.g., DNA-based and RNA-based, enveloped and non-enveloped 
viruses).   
The results of your viral inactivation studies should demonstrate that the sum of the log  
10
reduction in virus from selected processing steps and sterilization process(es) (i.e., the overall 
virus reduction factor) is sufficient to produce a safe product.14  For example, a device in which 
virus has been reduced by at least six logs greater than the virus concentration estimated in the 
unprocessed source material has historically been considered a safe device.  A final report 
describing these studies should be submitted in your premarket submission.  This report should 
discuss: 1) the animal species and tissue source material in the device as well as the amount of 
virus(es) that might be present in the source material (as identified by in-house research or 
published literature); 2) the appropriateness of the model viruses selected; 3) the relevance of 
the 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.  
 
ISO 22442-3 and the referenced ICH document15provide additional insight into the general 
design and interpretation of viral clearance studies.  ISO 22442-3 also recommends, whenever 
possible, to determine kinetics of viral inactivation to determine the theoretical time necessary 
to inactivate the total virus population.  While such information can be valuable in specific 
                                                            
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176, for more 
information regarding requesting FDA feedback through the Pre-Submission process. 
14 ISO 22442-1, Medical devices utilizing animal tissues and their derivatives  Part 1: Application of risk 
management 
15 Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin 
Q5a(R1), available at 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5A_R1/Step4/Q5A_R1__Gui
deline.pdf 
7 
    Contains Nonbinding Recommendations 
circumstances, FDA has found that measurement of the extent of viral inactivation at a single 
time point, rather than the multiple time points required for a kinetic study, may provide 
adequate evidence of viral clearance provided that: 1) the model system conditions evaluating 
viral inactivation closely resemble the conditions of device manufacture; 2) the model viruses 
tested accurately reflect the sensitivity of viral contaminates within the tissue to the inactivation 
methods tested; and 3) the extent of viral clearance observed in the study is significantly greater 
than the concentration of any pathogen present in the source tissue.   
While data demonstrating the viral inactivation properties associated with manufacturing and 
sterilization processes are often determined in laboratory studies with the intended product, 
published literature demonstrating the viral inactivation parameters of device 
manufacture/sterilization processes may be submitted in lieu of such testing when appropriate.  
FDA recommends that literature information be submitted when: 1) the publication contains 
sufficient information to evaluate the study results (e.g., test conditions, sample composition, 
and the control studies performed to validate the test conditions); 2) information is provided 
which explains why the published test samples accurately reflect your product; and 3) 
information is provided which explains why the published viral inactivation procedures 
accurately reflect your manufacturing/sterilization methods (e.g., reaction temperature, solution 
pH and ionic strength, and time of product exposure to the inactivation step as well as the 
concentration of proteins and other impurities in your product and the cited publication).   
Finally, please note that viral inactivation studies are not generally recognized to reflect the 
extent of prion contamination clearance or inactivation.  
D.  Transmissible Spongiform Encephalopathy-Specific 
Issues 
BSE is a degenerative disease that affects the central nervous system of cattle and is similar to 
other transmissible spongiform encephalopathies (TSEs) found in sheep (scrapie), deer (chronic 
wasting disease),16 and humans (Creutzfeldt-Jakob Disease or CJD and similar less common 
diseases).  Current data suggest that the incubation period of two to eight years after exposure is 
required before BSE symptoms are detectable.  Currently, there are no treatments for TSE 
diseases and no validated screening tests that detect infection in a live animal or human.  
Diagnosis is achieved by post-mortem microscopic examination of brain tissue, as well as 
assays using ELISA, Western Blot, or other techniques that detect abnormal forms of the prion 
protein. 
The BSE infectious agent is widely theorized to be a prion (i.e., an abnormally folded form of a 
normal protease-sensitive cellular prion protein [called PrPC or PrP(sen)]) that facilitates the 
                                                            
16 USDAs Animal and Plant Health and Inspection Services website concerning CWD (Chronic Wasting 
Disease), available at 
https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/sa_animal_disease_information/sa_alternate_livestock/sa
_cervid_health/sa_cwd 
 
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    Contains Nonbinding Recommendations 
conversion of additional normal cellular proteins to an abnormal misfolded infection-associated 
protease-resistant prion structure (called PrP(res) or PrPTSE).  PrP(res) has been detected in 
bovine brain, spinal cord, eye, ileum, lymph nodes, proximal colon, spleen, tonsil, dura mater, 
pineal gland, placenta, cerebrospinal fluid, pituitary, adrenal, distal colon, nasal mucosa, 
peripheral nerves, bone marrow, liver, lung, pancreas, and thymus.17 The detection of TSE 
infectivity in other tissues may occur in the future after data become available from more 
sensitive assays or larger animal studies.  Transmission has been experimentally demonstrated 
in animal studies.18 The TSE agent is known to be extremely resistant to traditional forms of 
disinfection and sterilization.  Please refer to FDAs website regarding BSE, available at 
https://www.fda.gov/AnimalVeterinary/ComplianceEnforcement/BovineSpongiformEncephalo
pathy/ucm2006517.htm, for the most current information.19 
Given the long incubation times before disease onset, the absence of a validated screening test 
for live animals, and vCJDs fatal outcome, we recommend that you collect and document the 
following information, in addition to the information listed in Sections A and B above, in your 
premarket submission for any material derived from ruminant animals (e.g., cattle, sheep, goats, 
cervids such as deer and elk) that have the potential to incubate a TSE infection: 
  whether animals were sourced from a country with Negligible, Controlled or Unknown 
BSE risk (per OIE);20,21 
  information concerning the long-term health of the herd (e.g., documented breeding 
history, animal traceability, absence of TSE disease and the surveillance program to 
detect a TSE); 
  the animal feed composition (e.g., animal feed history records, including recordation of 
commingling of feeds, and labeling of animal feed composition at distribution locations) 
(note that in 2008, FDA issued a final rule prohibiting certain material from being fed to 
ruminants, see 73 FR 22719); 
  the animal stunning and slaughter methods that reduce the risk of cross contaminating 
non-TSE tissues with material from tissues that could contain TSE; and 
  the specifics of the ante mortem and/or postmortem inspections (e.g., gross visual 
inspection, specific organs and anomalies exams, lab tests such as PrPTSE testing). 
In addition, the manufacturing facility should document 1) procedures for maintaining records 
                                                            
17 WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies (updated 2010), 
available at http://www.who.int/bloodproducts/tablestissueinfectivity.pdf 
18 Hamir, et.al., Experimental interspecies transmission studies of the transmissible spongiform encephalopathies 
to cattle comparison to bovine spongiform encephalopathy in cattle. Journal of Veterinary Diagnostic 
Investigation, May 2011, 23(3):407-420 
19 Additional resources include World Organization for Animal Health (OIE) BSE Situation in the world and 
annual incidence rate, available at http://www.oie.int/en/animal-health-in-the-world/bse-situation-in-the-world-
and-annual-incidence-rate/, and Variant CJD Cases Worldwide, available at 
http://www.cjd.ed.ac.uk/sites/default/files/worldfigs.pdf. 
20 OIE List of Bovine Spongiform Encephalopathy Risk Status of Member Countries, available at 
http://www.oie.int/animal-health-in-the-world/official-disease-status/bse/list-of-bse-risk-status/
21 78 FR 72979 
 
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    Contains Nonbinding Recommendations 
on the above cited items22 and 2) all information outlined above on each lot of product 
manufactured (Device History Record).23  If necessary to ensure the safety of the medical 
device, this information may be reviewed during inspection.   
Furthermore, it is important to keep in mind that the residence time of TSE-infectious material 
on surfaces is unknown and methods to completely assure removal of TSE-infectious material 
from surfaces have yet to be fully defined.  Cleaning processes developed to remove surface 
contamination in abattoirs after exposure to potentially TSE-infected animals (e.g., cattle, 
sheep, cervids such as deer or elk) may not have been fully characterized or validated for more 
critical sites or equipment used to manufacture devices.  Therefore, for facilities involved in 
device manufacture using tissue from potentially TSE-infected animals, your documentation 
should also identify when/whether any potentially TSE-infected material may have been 
previously processed in the facility and what steps were taken to address any potential 
contamination.  This information could include the information previously discussed under 
Manufacturing Controls for Animal Tissue Components in section IV.B. of this guidance and 
the dates of previous tissue processing (see also 21 CFR 820.50). 
Because screening assays cannot ensure TSE-free tissues from cows or other ruminant 
animals, the methods discussed above (e.g., monitoring animal feed, controlling animal 
husbandry, and tissue handling) reflect the best available approaches for preparing safe 
medical devices from animal tissue.  However, when a TSE-screening assay is validated to 
accurately identify TSE-contaminated tissues, FDA will consider revising this guidance as 
appropriate and recommending that such a test be introduced into the standard operating 
procedures for tissue collection and processing.  
                                                            
22 21 CFR 820.70 
23 21 CFR 820.184 
10