By Mark Durivage, Quality Systems Compliance LLC
ISO technical committee (ISO/TC) 194, Biological and clinical evaluation of medical devices, subcommittee (SC) 1, Tissue product safety, in collaboration with the European Committee for Standardization (CEN) technical committee (CEN/TC) 206, Biological and clinical evaluation of medical devices, in accordance with the agreement on technical cooperation between ISO and CEN (Vienna Agreement), has released ISO 22442-1:2020, Medical devices utilizing animal tissues and their derivatives — Part 1: Application of risk management and ISO 22442-2:2020, Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on sourcing, collection and handling.
These standards are both currently in their third edition and both cancel and replace the previous second editions of ISO 22442-1:2015 and ISO 22442-2:2015. This article will provide a high-level summary of the changes that were made to each of the standards.
ISO 22442 defines an animal as any vertebrate or invertebrate, explicitly excluding humans, and seeks to reduce or eliminate transmission of agents from animal tissues and their derivatives, including bacteria, molds, yeast, parasites, viruses, transmissible spongiform encephalopathy (TSE) agents, and unclassified pathogenic entities, to humans.
ISO 22442 for medical devices utilizing animal tissues and their derivatives consists of the following four documents:
- Part 1: Application of risk management
- Part 2: Controls on sourcing, collection and handling
- Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents
- Part 4: Principles for elimination and/or inactivation of transmissible spongiform encephalopathy (TSE) agents and validation assays for those processes
Information about the ISO 22442 series of standards can be found at: https://www.iso.org/search.html?q=22442
Animal tissues and their derivatives are used in the design and manufacture of medical devices to provide performance characteristics that have been chosen for their advantages over non-animal-based materials. The range and quantities of materials of animal origin in medical devices vary. These materials can comprise a major part of the device, product coating, or impregnation, or they can be used in the device manufacturing process.
ISO 22442 is applicable to medical devices including active implantable medical devices; however, ISO 22442 does not apply to in vitro diagnostic medical devices.
ISO 22442-1:2020 Part 1: Application of Risk Management
1) 4.4.2 Risk Control for Viruses and TSE agents
ISO 22442‑2 Controls on sourcing, collection, and handling can be especially difficult to comply with, especially when the materials of animal origin are derived from animals that are not raised on a farm, such as those that are wild caught, like fish and crabs.
When a manufacturer of the medical device is unable to comply with the relevant requirements of both ISO 22442‑2 and ISO 22442-3, exceptions are required to be documented and justified.
When the manufacturer is unable to provide information on the animal sourcing due to the animal species, as in the case of wild animals, the manufacturer is required to demonstrate the level of inactivation of transmissible agents through a validated manufacturing process to achieve an acceptable level of risk.
2) C.2 Collagen
Collagen is a fibrous protein occurring in vertebrates as a constituent of connective tissues and bones that yield gelatin and glue, which are extracted by boiling with water.
This section was updated to include clarification that source countries with “minimal exposure to bovine spongiform encephalopathy (BSE)” should be interpreted as countries with negligible exposure or countries on the Animal and Plant Health Inspection Service (APHIS) permitted list or from low-risk herds as defined in ISO 22442-2, and source countries with “limited exposure to BSE” should be interpreted in the same way as countries with controlled BSE risk. Additionally, the following web links were provided for reference:
The European Union has published documents on geographical BSE risks for a number of countries that are available on the website of the Scientific Steering Committee of the Commission of the European Union at: https://ec.europa.eu/food/safety/biosafety/food_borne_diseases/tse_bse_en
The permitted list published by the APHIS can be found at: https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-and-animal-product-import-information/animal-health-status-of-regions
The list of members of the World Organization for Animal Health recognized as having a negligible BSE risk in accordance with Chapter 11.4. of the Terrestrial Code can be found at: https://www.oie.int/animal-health-in-the-world/official-disease-status/bse/list-of-bse-risk-status#:~:text=Negligible%20BSE%20risk%20%20%20Argentina%20%20,%20Portugal%20%282%29%20%2012%20more%20rows%20
3) C.3.3 Bones as the Starting Material
National legislation now defines the process for the removal of vertebrae from the raw/starting materials from cattle of all ages from countries with limited exposure to BSE.
4) C.10 Peptones
Peptones are protein derivatives that are formed by the partial hydrolysis of proteins that are soluble in water, which is obtained by digesting protein with an enzyme.
This is a new section defining the requirements for the use of peptones by managing the risk primarily through the sourcing of animals of 30 months or less unless sourced from countries with a controlled BSE risk. Additionally, the animals must be deemed fit for human consumption by a veterinarian.
ISO 22442-1:2020 Part 2: Controls on Sourcing, Collection and Handling
1) 1 Scope
Note 1 was updated to explicitly identify TSE susceptible species, including bovine, ovine, caprine, deer, elk, mink, and cats. These species have documented instances of TSE. However, the only species known currently known to have transmitted TSE to humans is bovine.
2) 5.4 Inspection
This section references the potential application of validated biochemical in vitro testing for the presence of TSE in the source animal for direct use in medical devices that are not subject to a validated process to reduce TSE risk.
3) A.3.2.5 Particular circumstances
Stunning can destroy the brain and disseminate brain material into the bloodstream. The method of stunning is important to minimize the distribution of potentially infected brain material throughout the bloodstream during the slaughter process.
The web links in NOTE 1 on stunning techniques and the risk of dissemination of brain particles into the blood and carcass were updated and can be found at: https://ec.europa.eu/food/sites/food/files/safety/docs/sci-com_ssc_out245_en.pdf and https://www.efsa.europa.eu/en/efsajournal/pub/123.
4) Annex A
Annex A includes additional requirements relating to the application to bovine-sourced materials and other TSE relevant animal species, which now includes references to atypical BSE types such as H-type and L-type.
BSE exists in two forms, including the classical C-type and the atypical L-type and H-type. Classical C-type BSE resulted from feeding ruminant-derived proteins infected with prions to cattle. By prohibiting the practice of feeding cattle ruminant-derived proteins, the incidence of C-type BSE is on the decline. Evidence suggests a causal link between C-type BSE and variant Creutzfeldt-Jakob disease (vCJD) in humans. Atypical L-type and H-type BSE spontaneously occur infrequently in older cattle. There is no evidence to suggest that atypical L-type or H-type BSE have been transferred to humans.
This article was meant as a brief overview of the updates to ISO 22441-1 and 22442-2. I suggest your organization purchase copies of these standards and perform a complete comprehensive regulatory assessment to ensure your organization is compliant with the recent changes.
- ISO 22442-1:2020 Medical devices utilizing animal tissues and their derivatives — Part 1: Application of risk management
- ISO 22442-2:2020 Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on sourcing, collection and handling.
- ISO 22442-3:2007 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 22442-4:2010 Medical devices utilizing animal tissues and their derivatives — Part 4: Principles for elimination and/or inactivation of transmissible spongiform encephalopathy (TSE) agents and validation assays for those processes
About The Author:
Mark Allen Durivage has worked as a practitioner, educator, consultant, and author. He is managing principal consultant at Quality Systems Compliance LLC, an ASQ Fellow, and an SRE Fellow. Durivage primarily works with companies in FDA-regulated industries (medical devices, human tissue, animal tissue, and pharmaceuticals), focusing on quality management system implementation, integration, updates, and training. Additionally, he assists companies by providing internal and external audit support, as well as FDA 483 and warning letter response and remediation services. He earned a BAS in computer-aided machining from Siena Heights University and an MS in quality management from Eastern Michigan University. He holds several certifications including; CRE, CQE, CQA, CSSBB, RAC (Global), and CTBS. He has written several books available through ASQ Quality Press, published articles in Quality Progress, and is a frequent contributor to Life Science Connect. Durivage resides in Lambertville, Michigan. Please feel free to email him at firstname.lastname@example.org and connect with him on LinkedIn.