Animal Derived Materials in Medical Applications

Any materials derived from animal sources are called Animal-derived materials (ADM). Day today’s life examples of ADMs are fat, flesh, blood, milk, and eggs. It is widely used in the food, cosmetics, pharmaceuticals, and medical devices industries. Recently many regulations are issued guidelines/ policies regarding the use of animal-derived materials all over these industries 

ADMs are used in polymers to stabilize formulations, enhance properties, and aid in processing. Stearate is the most commonly used ADM in the polymer. It is used to impart lubricity, improve flow and inactivate polymerization catalysts. Due to its wide properties, it is found in many polymers like grades of polyethylene (PE) and polypropylene (PP).
Some examples of Stearates are listed out here:

Stearic Acid (Found in various animal and plant fats, Animal-derived stearate acid is often a product of tallow – it is a foundational Stearate for further derivatization)

Calcium Stearate (Used as a lubricant, dispersant, stabilizer & nucleating agent, it enhances release properties. Commonly used as an acid scavenger in PE, PP, PS & PVC to improve stability)

Zinc Stearate (Used to provide enhanced lubricity & thermal stability, improves pigment wetting. Commonly used in polyolefin sand PVC as a lubricant)

Ethylene Bis-stearamide (Used as a lubricant and dispersion aid. It has anti-tack properties & will not degrade materials (non-reactive with condensation resins))

The outbreaks of bovine spongiform encephalopathy (BSE; “mad cow disease”), Transmissible spongiform encephalopathies (TSEs) diseases are the reason for raised concerns over the safety of ADMs. In addition, Creutzfeldt-Jakob Disease (CJD), a human neurodegenerative disorder increased the concern.

– This disease is rapidly progressive and always fatal
– This disease causes brain infection which leads to death usually within 1 year of onset of illness.
– A variant of CJD is linked to outbreaks of “mad cow disease”. It is believed that similar prions are responsible for both diseases

Polymer/ additives containing ADMs are used to manufacture medical device components (i.e., coatings, tubing, connectors, and packaging). ADMs can comprise a major part of a finished device (i.e., bovine heart valves, bone substitutes, collagen injection). Medical resins that may contain ADMs include PE, PP, PVC, Acetal, TPU, TPV, etc. These materials may carry a risk of transmitting infectious disease when improperly collected, stored, or processed. Equipment manufacturers should ensure that the material suppliers provide information on the safe handling and processing of raw materials used in their products.   

The Food and Drug Administration (FDA) issued guidance regarding the use of animal-derived material in medical device manufacturing, the latest one published in March 2019.
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.
For streamlined approval, medical manufacturers should obtain the following documentation for all ADMs used in their devices if available. This information may be requested by the FDA as part of a 510k clearance or other submissions.
– Animal species used
– Specific tissue(s) used
– Animal’s country of origin and country of residence
– Methods for monitoring animal’s health
– Long-term health of the herd (breeding history, vaccinations, inspections)
– Animal feed composition & feed history
– USDA status of the abattoir
– Animal age at sacrifice, sacrifice methods
– Pre & post mortem inspections
– Methods and conditions for transporting animal tissue

The Commission of the European Union (EU) published the “TSE Directive” in 2003. In support of this Directive, the Commission issued revised regulations regarding the use of TSE-relevant animal tissues in medical devices. In support of this Directive, the Commission has recently issued revised regulations (722/2012) regarding the use of TSE-relevant animal tissues and products found in a wide range of medical devices. These regulations impose additional compliance requirements on medical manufacturers, including assessment and management practices intended to reduce the potential risk of TSE transmission. Under the new EU MDR (2017/745) also there is no exception. EU MDR insist the following :

Section 13 – For devices manufactured utilizing tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable the following shall apply

• (a) (a) Where feasible taking into account the animal species, tissues, and cells of animal origin, or their derivatives, shall originate from animals that have been subjected to veterinary controls that are adapted to the intended use of the tissues. Information on the geographical origin of the animals shall be retained by manufacturers;
  (b) (b) Sourcing, processing, preservation, testing, and handling of tissues, cells, and substances of animal origin, or their derivatives, shall be carried out to provide safety for patients, users, and, where applicable, other persons. In particular safety concerning viruses and other transmissible agents shall be addressed by implementation of validated methods of elimination or viral inactivation in the course of the manufacturing process, except when the use of such methods would lead to unacceptable degradation compromising the clinical benefit of the device;
  (c) (c) In the case of devices manufactured utilizing tissues or cells of animal origin, or their derivatives, as referred to in Regulation (EU) No 722/2012 the particular requirements laid down in that Regulation shall apply.

References:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-devices-containing-materials-derived-animal-sources-except-vitro-diagnostic-devices

EUR-Lex – 02017R0745-20170505 – EN – EUR-Lex (europa.eu)