biomats2

FDA

US Food and Drug Administration; regulates products including drugs, medical devices, biologics, and combination products

Does the FDA directly regulate biomaterials?

No. The FDA regulates biomaterials indirectly based on their intended use as a medical device, drug, biologic, or combination product

CDER

Center for Drug Evaluation and Research; FDA division responsible primarily for drugs

CDRH

Center for Devices and Radiological Health; FDA division responsible primarily for medical devices

CBER

Center for Biologics Evaluation and Research; FDA division responsible primarily for biologics

Combination product

A product involving two or more regulated components, such as drug/device, biologic/device, drug/biologic, or drug/device/biologic

Class I device

Medical device with minimal risk and the least regulatory burden; generally subject to general controls

Class II device

Medical device with greater risk than Class I; usually requires FDA clearance before marketing, predominantly through 510(k)

Class III device

Highest-risk medical device category; subject to the strictest regulatory controls and predominantly regulated through PMA

Class I examples

Bandages, adjustable beds, many surgical instruments, manual stethoscopes

Class II examples

Mercury dental amalgam, electronic stethoscopes, most catheters, needles, monitoring devices

Class III examples

Cardiac assist pumps, bone grafts, heart valves, orthopedic implants, arterial grafts, pacemakers

General controls

Basic FDA controls applied to medical devices, particularly Class I devices

PMA

Premarket Approval; regulatory pathway predominantly used for Class III and some new Class II devices

PMA requirements

Typically involves substantial evidence of safety and effectiveness and may include animal studies, safety studies, and small- and large-scale human studies

PMA timeline

Can take years to decades depending on the device and evidence required

510(k)

Premarket notification pathway predominantly used for Class II devices

510(k) purpose

To demonstrate that a new device is substantially equivalent to an existing predicate device

Predicate device

A legally marketed device used as the comparison device for a 510(k); generally one commercially distributed in the US before May 28, 1976 or previously determined substantially equivalent

Substantial equivalence

The new device has the same intended use and same technological characteristics as the predicate, OR differences do not raise different questions of safety and effectiveness

510(k) marketing requirement

A device cannot be commercially distributed until FDA issues a substantial-equivalence determination/letter

PMA vs 510(k)

PMA generally requires more extensive evidence and is predominantly used for Class III devices; 510(k) primarily demonstrates substantial equivalence for Class II devices

HCTP

Human Cells, Tissues, and Cellular and Tissue-Based Products pathway/category listed in the module

IND

Investigational New Drug pathway; relevant when drug action drives the function or output of the device/product

HDE

Humanitarian Device Exemption; applies when a patient population has no viable treatment options

IDE

Investigational Device Exemption; allows testing of devices with limited risk, commonly non-implanted devices

Minimally manipulated human products

One of the regulatory pathway/categories discussed for human-derived products

How to determine an FDA regulatory pathway

Ask whether a similar material/device already exists for the same indication, what the primary mechanism of action is, and what claims will be made

FDA device-specific guidance

Documents that provide insight into appropriate testing and preparation for regulatory clearance

Purpose of FDA guidance

Helps researchers choose appropriate tests and can reduce wasted time, money, and animals

Is FDA guidance the same as law?

No. Guidance provides recommendations and insight but is not the same as rigid laws or regulations

Where to find FDA guidance

FDA guidance document search

ISO 10993

Internationally accepted series of standards for evaluating the biocompatibility of medical devices and managing biological risk

FDA and ISO 10993

The FDA leverages ISO 10993 standards when evaluating the biocompatibility of medical devices

Does every device need every ISO 10993 test?

No. Test selection depends on the device, materials, intended use, and associated biological risks

ISO 10993-3

Genotoxicity, carcinogenicity, and reproductive toxicity

ISO 10993-4

Hemolysis and blood interaction

ISO 10993-5

Cytotoxicity

ISO 10993-11

Systemic toxicity

ISO 10993-18

Chemical characterization of materials

ISO 10993-19

Surface analysis

ISO 10993-3 memory trick

3 = Genetic

ISO 10993-4 memory trick

4 = Blood

ISO 10993-5 memory trick

5 = Cells

ISO 10993-11 memory trick

11 = Systemic

ISO 10993-18 memory trick

18 = Chemistry

ISO 10993-19 memory trick

19 = Surface

Biocompatibility

The evaluation of how a medical device/material interacts biologically with the body and the biological risks associated with that interaction

Biological risk

An adverse biological effect that may result from interaction between a device/material and the body

Chemical characterization

Identification/evaluation of the chemical composition of materials used in a medical device

Surface analysis

Evaluation of the surface characteristics of a material/device

Hemolysis

The destruction or damage of red blood cells; evaluated under ISO 10993-4

Cytotoxicity

The degree to which a material or its extracts are toxic to cells; evaluated under ISO 10993-5

Systemic toxicity

Toxic effects that occur throughout the body rather than being limited to the local site; evaluated under ISO 10993-11

Genotoxicity

Damage to genetic material; evaluated under ISO 10993-3

Carcinogenicity

The potential of a material/exposure to contribute to cancer development; included under ISO 10993-3

Reproductive toxicity

Adverse effects on reproductive function or development; included under ISO 10993-3

ClinicalTrials.gov

A database that can be searched for US clinical trials and related study information

How to search ClinicalTrials.gov

Search by disease/condition or by a specific biomaterial intervention and then inspect entries, tabs, and filters

ASTM

Organization that develops and publishes voluntary consensus technical international standards for materials, products, systems, and services

Purpose of ASTM standards

Provide standardized and robust methods for characterizing materials and testing products

ASTM and biomaterials

ASTM standards can provide standardized test methods for biomaterials characterization

Can ASTM standards be required?

Yes. They can be used exactly when required by regulation or adapted when appropriate with a clear explanation

ASTM Compass

A resource/database for accessing ASTM standards

ISO

International standards organization providing broad global standards for consistency across industries

Purpose of ISO standards

Provide guidance for establishing and executing processes and tests across industries

ISO and biomaterials

ISO provides standards related to areas such as biocompatibility, GMP manufacturing, and sterility

ISO vs ASTM

ISO provides broad international standards and guidance, while ASTM focuses heavily on voluntary consensus technical standards and standardized test methods

USP

United States Pharmacopeia; provides documentary standards, particularly related to drugs and drug-related materials

USP Documentary Standards

Standards covering areas such as manufacture, storage, and testing, predominantly for drugs

USP benchmarks

Standards/benchmarks for identity, purity, strength, and performance

GMP

Good Manufacturing Practice; a type of standard/framework listed in the module

Standards discussed in the module

ISO, ASTM, USP, and GMP

Why use standards in biomaterials research?

They provide established approaches for testing, characterization, manufacturing, and evaluating materials

Sterility

The condition of being free from viable microorganisms

Sterilization

A process intended to eliminate viable microorganisms from a device/material

FDA Sterility and Pyrogenicity Guidance Document

FDA guidance addressing sterility and pyrogenicity considerations for medical devices

Part V of the FDA Sterility and Pyrogenicity Guidance

Document section discussed for sterilization methods and considerations

Established sterilization methods

Sterilization methods recognized/established for medical devices and discussed in FDA guidance

Novel sterilization methods

New or less-established sterilization approaches that may require additional consideration/evaluation

Sterilization method selection

Should be based on the specific biomaterial/device and whether the sterilization process is suitable for that material and intended use

Why can't all devices use the same sterilization method?

Different materials and device designs can respond differently to sterilization processes, so suitability must be evaluated for the specific device

Human/animal tissue and sterilization

Sterilization of devices incorporating human or animal tissues has additional considerations and is outside the scope of the discussed FDA guidance

Viral inactivation

Processes used to reduce/eliminate viruses in materials containing human or animal tissues

FDA branch for human/animal tissue sterilization

Consult the responsible FDA branch for applicable requirements and guidance

Biomaterial regulatory strategy

The regulatory approach depends on intended use, device classification, mechanism of action, existing predicates, and claims

Medical device intended use

A key factor in determining how the FDA regulates a product

Why intended use matters

It helps determine whether a product is regulated as a device, drug, biologic, or combination product

Class I regulatory burden

Lowest of the three device classes

Class II regulatory burden

Moderate; usually requires FDA clearance

Class III regulatory burden

Highest; generally requires PMA and substantial evidence of safety and effectiveness

Which device class is highest risk?

Class III

Which device class is lowest risk?

Class I

Which device class commonly uses 510(k)?

Class II

Which device class commonly uses PMA?

Class III

What does 510(k) demonstrate?

Substantial equivalence to a predicate device

What does PMA demonstrate?

Safety and effectiveness through substantial evidence

What is the main purpose of a predicate device?

To provide an existing legally marketed comparison for determining substantial equivalence

What must a 510(k) device have in relation to its predicate?

The same intended use and same technological characteristics, or differences that do not raise different questions of safety and effectiveness

What happens after FDA determines substantial equivalence?

The device can proceed toward commercial distribution subject to applicable requirements