ASTM F3089-23

ASTM F3089-23 - 1.1.2023

Significance and Use

4.1?The objective of this document is to provide guidance in the production, characterization, testing, and standardization of: (1) polymerizable collagen starting materials; and (2) collagen polymeric materials produced with polymerizable collagen formulations, used for surgical implants, substrates for TEMPs, vehicles for therapeutic cells and molecules, and 3D in-vitro tissue systems for basic research, drug development, and toxicity testing. This guide can be used as an aid in the selection, characterization, and standardization of the appropriate polymerizable collagen starting formulations as well as collagen polymeric materials prepared from polymerizable collagens for a specific use. Not all tests or parameters are applicable to all uses of collagen and users are expected to select and justify a subset of the tests for characterization purposes.

4.2?This guide can be used by the following types of users:

4.2.1?Manufacturers of polymerizable collagens and collagen polymeric materials who wish to set specifications for their products or provide characterization data for customers or users. They may also use the terminology and characterization sections to specify and differentiate the properties of polymerizable collagens and collagen polymeric materials.

4.2.2?Producers of collagen polymeric materials that use polymerizable collagen as starting materials. Producers may use this guide to evaluate and characterize multiple sources of polymerizable collagen. They may also use this guide to assist with evaluation and comparison of single or multiple sources of polymerizable collagen and collagen polymeric materials.

4.2.3?Researchers may use this guide as a reference for properties and test methods that can be used to reproducibly evaluate polymerizable collagens and collagen polymeric materials.

4.3?The collagen covered by this guide may be used in a broad range of applications, forms, or medical products, for example (but not limited to) wound and hemostatic dressings, surgical implants or injectables (including in-situ forming), hybrid medical devices, TEMPs, injectable (including in-situ forming) or implantable delivery vehicles for therapeutic cells, molecules, and drugs, and 3D in-vitro tissue systems or models for basic research, drug development, and toxicity testing. The practical application of polymerizable collagens and collagen polymeric materials should be based, among other factors, on biocompatibility, application-specific performance measures, as well as chemical, physical, and biological test data. Recommendations in this guide should not be interpreted as a guarantee of success for any specific research or medical application.

4.4?The following general areas should be considered when determining if the collagen supplied satisfies requirements for use in the above mentioned medical and research applications: source of polymerizable collagen, impurities profile, and comprehensive chemical, physical, and biological characterization and testing.

4.5?The following documents or other relevant guidance documents from appropriate regulatory bodies relating to the production, regulation, and regulatory approval of devices, biologics, drugs, and combination products should be considered when determining if the collagen supplied satisfies requirements for use in medical and research products, including TEMPs, therapeutic delivery vehicles, and 3D in-vitro tissue systems:

FDA CFR:

21 CFR 3: Product Jurisdiction:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=3

21 CFR 58: Good Laboratory Practice for Nonclinical Laboratory Studies:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=58

FDA/CDRH CFR and Guidances:

21 CFR Part 803: Medical Device Reporting:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=803

21 CFR 812: Investigational Device Exemptions:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=812

21 CFR 814: Premarket Approval of Medical Devices:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=814

21 CFR 820: Quality System Regulation:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=820

Design Control Guidance for Medical Device Manufacturers:

http://www.fda.gov/cdrh/comp/designgd.pdf

Preproduction Quality Assurance Planning Recommendations for
Medical Device Manufacturers (FDA 90-4236):

http://www.fda.gov/cdrh/manual/appende.html

The Review and Inspection of Premarket Approval Applications
under the Bioresearch Monitoring ProgramDraft Guidance
for Industry and FDA Staff:

http://www.fda.gov/cdrh/comp/guidance/1602.pdf

FDA/CDRH Search Engines:

CDRH Guidance Search Engine:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfggp/
search.cfm

CDRH Premarket Approval (PMA) Search Engine:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/
pma.cfm

CDRH 510(k) Search Engine:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/
pmn.cfm

CDRH Recognized STANDARDS Search Engine:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/
search.cfm

FDA/CBER CFR and Guidances:

21 CFR 312: Investigational New Drug Application:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=312

21 CFR 314: Applications for FDA Approval to Market a New Drug:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=31

21 CFR 610: General Biological Products Standards:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=610

21 CFR 1271: Human Cells, Tissues and Cellular and Tissue-Based Products:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?CFRPart=1271

Cellular & Gene Therapy Guidances and Other Publications:

http://www.fda.gov/cber/genetherapy/gtpubs.htm

Human Tissue Guidances and Other Publications:

http://www.fda.gov/cber/tissue/docs.htm

CBER Product Approval Information:

http://www.fda.gov/cber/efoi/approve.htm

21 CFR 600, 601 BLA Regulations:

http://www.access.gpo.gov/nara/cfr/waisidx_07/21cfrv7_07.html

21 CFR 210, 211 GMP Regulations:

http://www.access.gpo.gov/nara/cfr/waisidx_07/21cfr210_07.html

1. Scope

1.1?This guide is intended to provide characteristics, properties, test methods, and standardization approaches for evaluation and identification of specific polymerizable collagen formulations and collagen polymeric materials produced with these formulations.

1.2?This guide focuses on characterization of purified polymerizable forms of type I collagen, which is the most abundant collagen in mammalian connective tissues and organs, including skin, bone, tendon, and blood vessels. Polymerizable type I collagen may be derived from a variety of sources including, but not limited to, animal or cadaveric tissues, cell culture, recombinant cell culture, and chemical synthesis.

1.2.1?This guide covers evaluation of polymerizable collagens and collagen polymeric materials prepared from polymerizable collagens for use as a starting material for wound and hemostatic dressings, surgical implants, substrates for tissue-engineered medical products (TEMPs), delivery vehicles for therapeutic cells or molecules, and 3D in-vitro tissue systems for basic research, diagnostics, drug development, and toxicity testing. Most collagen products on the market today are regulated as devices since their primary intended purpose is not achieved through chemical action within or on the body. However, a medical product comprising polymerizable collagens or collagen polymeric materials may be regulated as a device, biologic, drug, or combination product depending on its intended use and primary mode of action.

1.2.2?Polymerizable collagen or collagen self-assembly implies that the collagen composition exhibits spontaneous macromolecular assembly from its components without the addition of exogenous factors such as cross-linking agents. Polymerizable collagens may include but are not limited to: (1) tissue-derived monomeric collagens, including tropocollagen or atelocollagen, and oligomeric collagens; (2) collagen proteins and peptides produced through in vitro cell culture, with or without using recombinant technology; and (3) chemically synthesized collagen mimetic peptides. It should be noted that the format of collagen polymeric material products also will vary and may include injectable solutions that polymerize in situ as well as preformed sheets, particles, spheres, fibers, sponges, matrices/gels, coatings, films, and other forms.

1.2.3?This guide may serve as a template for characterization and standardization of type I fibrillar collagen or other collagen types that demonstrate polymerization or self-assembly.

1.3?This guide does not provide a significant basis for assessing the biological safety (biocompatibility) of polymerizable collagens and collagen polymeric materials. While the ability of collagen polymeric materials to guide cellular responses through provision of cellular adhesion and proteolytic domains as well as physical constraints (for example, structural, cell-matrix traction force) has been well documented through extensive clinical and basic research studies (1-5),2 users are directed to the ISO 10993 series for evaluating biological risks of medical devices. The biocompatibility and appropriateness of use for a specific application is the responsibility of the product manufacturer.

1.4?The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.

1.5?The following precautionary caveat pertains only to the test method portion, Sections 6 and 7, of this guide: This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.6?This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.

2. Referenced Documents

F1903-18	Standard Practice for Testing for Cellular Responses to Particles in vitro
ISO 10993–10	Biological Evaluation of Medical Devices--Part 10: Tests for Irritation and Delayed-Type Hypersensitivity
USP 30/NF 19	Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin
ICH S2B	Guidance for Industry S2B Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals 62 FR 62472 (1997)
ICH S5A	Guideline for Industry S5A Detection of Toxicity to Reproduction for Medicinal Products 59 FR 48746 (1994)
F895-11(2016)	Standard Test Method for Agar Diffusion Cell Culture Screening for Cytotoxicity
F981-23	Standard Practice for Assessment of Muscle and Bone Tissue Responses to Long-Term Implantable Materials Used in Medical Devices
ISO 13408–1	Aseptic Processing of Health Care Products--Part 1: General Requirements
ISO 14971	Medical Devices--Application of Risk Management to Medical Devices
ISO 22442–1	Animal Tissues and their Derivatives Utilized in the Manufacture of Medical Devices--Part 1: Analysis and Management of Risk
F813-20	Standard Practice for Direct Contact Cell Culture Evaluation of Materials for Medical Devices
ISO 10993–17	Methods for Establishment of Allowable Limits for Leachable Substances Using Health-Based Risk Assessment
F749-20	Standard Practice for Evaluating Material Extracts by Intracutaneous Injection in the Rabbit
E1298-06	Standard Guide for Determination of Purity, Impurities, and Contaminants in Biological Drug Products (Withdrawn 2014)
F619-20	Standard Practice for Extraction of Materials Used in Medical Devices
F756-17	Standard Practice for Assessment of Hemolytic Properties of Materials
F763-22	Standard Practice for Short-Term Intramuscular Screening of Implantable Medical Device Materials
F720-17	Standard Practice for Testing Guinea Pigs for Contact Allergens: Guinea Pig Maximization Test
F748-16	Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
ISO 22442–2	Animal Tissues and their Derivatives Utilized in the Manufacture of Medical Devices--Part 2: Controls on Sourcing, Collection, and Handling
ISO 22442–3	Animal Tissues and their Derivatives Utilized in the Manufacture of Medical Devices--Part 3: Validation and the Elimination and/or Inactivation of Virus and Transmissable Agents
United States Pharmacopeia (USP), Edition XXX (30)
ICH S2A	Guideline for Industry S2A Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals 61 FR 18199 (1996)
ICH S1C(R)	Guidance for Industry Addendum to Dose Selection for Carcinogenicity Studies of Pharmaceuticals: Addition of a Limit Dose and Related Notes 62 FR 64259 (1997)
ICH Q1A ICH	Harmonized Tripartite Guidance for Stability Testing of New Drug Substances and Products (September 23, 1994)
U.S. Food and Drug Administration (FDA and Committee for Proprietary Medicinal Products (CPMP), 1998	International Conference on Harmonization (ICH), Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin, Consensus Guideline ICH Viral Safety Document: Step 5
FDA	Guidance for Industry Pyrogen and Endotoxins Testing: Questions and Answers, DHHS, June 2012
F2148-18	Standard Practice for Evaluation of Delayed Contact Hypersensitivity Using the Murine Local Lymph Node Assay (LLNA)
U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER), 1993	Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals
U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER), 1997	Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use, 94D-0259
FDA	Interim Guidance for Human and Veterinary Drug Products and Biologicals, Kinetic LAL techniques, DHHS, July 15, 1991
ANSI/AAMI/ISO 11737-1: 2006	Sterilization of Medical Devices--Microbiological Methods--Part 1: Estimation of Bioburden on Product
ANSI/AAMI/ISO 11737-2: 1998	Sterilization of Medical Devices--Microbiological Methods--Part 2: Tests of Sterility Performed in the Validation of a Sterilization Process
AAMI TIR No. 19-1998	Guidance for ANSI/AAMI/ISO 10993-7: 1995, Biological Evaluation of Medical Devices--Part 7: Ethylene Oxide Sterilization Residuals
AAMI/ISO 14160-1998	Sterilization of Single-Use Medical Devices Incorporating Materials of Animal Origin--Validation and Routine Control of Sterilization by Liquid Chemical Sterilants
AAMI ST67/CDV-2: 1999	Sterilization of Medical Devices--Requirements for Products Labeled Sterile
F1983-23	Standard Practice for Assessment of Selected Tissue Effects of Absorbable Biomaterials for Implant Applications
European Pharmacopeia 5.0
21 CFR Part 820	Quality System Regulation
Federal Register Vol. 43	No. 141, Friday, July 21, 1978
21 CFR Parts 207, 807, and 1271	Human Cells, Tissues and Cellular and Tissue-Based Products, Establishment Registration and Listing
Federal Register, Vol. 66	No. 13, Jan. 19, 2001/Rules and Regulations, p. 5447
Federal Register, Vol. 72	No. 8, Jan. 12, 2007, pp. 1581-1619, Proposed Rule: Use of Materials Derived from Cattle in Medical Products Intended for Use in Humans and Drugs Intended for Use in Ruminants
21 CFR 312	Investigational New Drug Application
21 CFR Part 1271, Part C	Suitability Determination for Donors of Human Cell and Tissue-based Products, Proposed Rule
ICH S1A	Guideline for Industry S1A The Need for Long-term Rodent Carcinogenicity Studies of Pharmaceuticals 61 FR 8153 (1996)
ICH S1B	Guidance for Industry S1B Testing for Carcinogenicity of Pharmaceuticals 63 FR 8983 (1998)
ICH S1C	Guideline for Industry S1C Dose Selection for Carcinogenicity Studies of Pharmaceuticals 60 FR 11278 (1995)
ICH S5B	Guidance for Industry S5B Detection of Toxicity to Reproduction for Medicinal Products: Addendum on Toxicity to Male Fertility 61 FR 15360 (1996)
Current Good Tissue Practice for Manufacturers of Human Cellular and Tissue-Based Products	Inspection and Enforcement. Proposed Rule. Federal Register/Vol. 66, No. 5/January 8, 2001/Proposed Rules, pp. 1552-1559
Guidance for Screening and Testing of Donors of Human Tissue Intended for Transplantation	Availability. Federal Register/Vol. 62, No. 145/July 29, 1997/Notices Draft Guidance for Preclinical and Clinical Investigations of Urethral Bulking Agents used in the Treatment of Urinary Incontinence. November 29, 1995. (ODE/DRARD/ULDB), Document No. 850
Guidance for Industry and for FDA Reviewers	Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices), November 6, 1998, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health
CFR?610.13(b)	Rabbit Pyrogen Assay
ICH M3	Guidance for Industry M3 Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals 62 FR 62922 (1997)
F1905-98	Standard Practice for Selecting Tests for Determining the Propensity of Materials to Cause Immunotoxicity
F1906-98	Standard Practice for Evaluation of Immune Responses In Biocompatibility Testing Using ELISA Tests, Lymphocyte, Proliferation, and Cell Migration
F1904-23	Standard Guide for Testing the Biological Responses to Medical Device Particulate Debris and Degradation Products in vivo
ISO 10993–9	Framework for Identification and Quantification of Potential Degradation Products
ISO 10993–1	Biological Evaluation of Medical Devices--Part 1: Evaluation and Testing with a Risk Management Process
ISO 10993–3	Tests for Genotoxicity, Carcinogenicity and Reproductive Toxicity
F1251-89(1995)	Standard Terminology Relating to Polymeric Biomaterials in Medical and Surgical Devices
F1439-03(2018)	Standard Guide for Performance of Lifetime Bioassay for the Tumorigenic Potential of Implant Materials