Biocompatibility Testing of Medical Devices - Standards Specific Information for the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program: Guidance for Industry, Accreditation Bodies, Testing Laboratories, and Food and Drug Administration Staff | Guideline Explorer

Description

This guidance provides information on how the Biological Evaluation of Medical Devices standards are incorporated into the Pilot Accreditation Scheme for Conformity Assessment Program (hereafter referred to as the ASCA Pilot). The ASCA Pilot is described in FDA's guidanceThe Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

4

Medical Devices

Medical devices intended for human use; Approved or cleared medical devices

absorbable or in situ polymerizing devices

not eligible for biocompatibility testing under the ASCA Pilot

Absorbable and in situ polymerizing devices

Excluded from the ASCA Pilot for biocompatibility testing.; excluded from the ASCA Pilot

Devices containing nanomaterials

Excluded from the ASCA Pilot for biocompatibility testing.; excluded from the ASCA Pilot; not eligible for biocompatibility testing under the ASCA Pilot

Stakeholders

10

Accreditation Bodies

Guidance for industry, accreditation bodies, and testing laboratories.; participate in the ASCA Pilot

Test Laboratory

Test Laboratory may also be requested to provide a rationale.; Entity responsible for conducting tests and providing rationales

Manufacturer

Entity responsible for submitting NDINs

device manufacturer

Entity responsible for specifying acceptance criteria and risk management; Responsible for specifying essential performance and submitting premarket submissions.; supplied by the device manufacturer to the testing laboratory

ASCA-accredited testing laboratory

Laboratories authorized to perform testing within a specific scope under the ASCA Pilot.

quality assurance unit

personnel involved in study oversight per GLP

study director

personnel required to sign biological study reports

Toxicologists

Technical experts involved in determining test validity.

Testing Laboratories

Guidance for industry, accreditation bodies, and testing laboratories.; conduct testing under ASCA Accreditation

Study directors

Technical personnel required to have specific degrees and experience.; Personnel responsible for determining acceptability of test validity.

Regulatory Context

Regulatory Activities

4

Accreditation Scheme for Conformity Assessment

FDA is converting the ASCA program from a pilot to a permanent program.

ASCA Pilot Program

Accreditation Scheme for Conformity Assessment

Premarket Submission

Regulatory submission for FDA evaluation of safety and effectiveness; regulatory filing containing software documentation; submission of software documentation to FDA

Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program

The program for which testing laboratories seek accreditation for medical device biocompatibility.; materials are not eligible for biocompatibility testing under the ASCA Pilot; Standards Specific Information for the ASCA Pilot Program; Standards Specific Information for the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program; during the ASCA Pilot; complete test report should be included with ASCA Summary Test Report during the ASCA Pilot; ASCA Pilot program for conformity asses

Document Types

7

Declaration of Conformity

Premarket submission contents include a Declaration of Conformity.; Document included in premarket submission; Example ASCA Declaration of Conformity (DOC) for Basic Safety

ASCA Test Article Prep SOP

Standard operating procedure for preparing test articles.

complete test report

The full documentation of testing, required if deviations occur.; Full documentation required if test validity criteria are not met or positive response is found

ASCA Summary Test Report

Supplemental documentation provided by laboratories to manufacturers; Documentation summarizing testing conducted by an ASCA-accredited laboratory; Information provided by the testing laboratory to the manufacturer; Documentation artifact for the ASCA program; The submitted ASCA Summary Test Report may not be adequate to support the ASCA DOC during suspension.; Report summarizing test results under ASCA; Ensure ASCA summary test report(s) include the elements in the ASCA Program guidances.

Equipment records

Documentation for adding, deleting, or maintaining equipment information.

Summary Test Report

Example ASCA Summary Test Report provided in Appendix B.

Supplemental Information Sheet

provides additional information for each standard listed in the database

Attributes

4

Hemolytic index

Calculated value used to interpret hemolysis test results.; test article scores of ≥2% HI

Primary Irritation Index

Table 2 Summary of Primary Irritation Index.

ASCA Accreditation Status

The status of a laboratory's accreditation (e.g., suspended or active) at the time of testing.

scope of ASCA Accreditation

The specific standards and test methods a laboratory is accredited to perform.

Technical Details

Substances

10

dinitrochlorobenzene

strong sensitizers such as 0.1-0.5% dinitrochlorobenzene (DNCB).

Cobra Venom Factor

Positive control used in the test

Whole Blood

Examples of specimen types include but are not limited to: whole blood

Human Plasma

Test medium for complement activation

Normal Human Serum

Test medium for complement activation

Magnesium and Calcium Free PBS

Used as an extraction solvent and diluent.

Sodium Chloride

Extraction Solvent: 0.9% Sodium Chloride (SC)

Sesame Oil

Extraction Solvent; Alternative nonpolar extraction solvent

Dinitrochlorobenzene (DNCB)

Dinitrochlorobenzene (DNCB) Positive Control

MEM with 5-10% animal serum

A common extraction solvent used in cytotoxicity testing.; Extraction solvent used in the cytotoxicity test

Testing Methods

10

MEM Elution Cytotoxicity

Specific analytical procedure for biocompatibility; ISO 10993-5 Clause 8.2; A specific biocompatibility test method described in Appendix D.

Fluid Path Extractions

the extraction was conducted using protocols specific to fluid path

Direct and Indirect Hemolysis

Test Method & Procedure: Direct and Indirect Hemolysis [SOP XXX].

Sensitization

Biocompatibility endpoint

Magnusson and Kligman grades

if the Magnusson and Kligman grades of 1 or greater observed in the test group

Closed Patch Sensitization

ISO 10993-10 test method; biocompatibility test method

Dermal Irritation

Test Method-Specific ASCA Specifications: Dermal Irritation; Table 1 Summary of Scores for Dermal Irritation.; biocompatibility test method

Cytotoxicity - MEM Elution

Example ASCA Summary Test Report for Biocompatibility Testing of Medical Devices: Cytotoxicity - MEM Elution

complement activation testing

biological evaluation assessment using SC5b-9

hemolysis testing

biological evaluation assessment

Processes

6

Extraction

Process involving a filtration step or solvent other than water or alcohol.

Fluid Path Extractions

For fluid path devices or components, the extraction was conducted using protocols specific to fluid path.; Extraction protocols specific to fluid path devices or components; Extraction conducted using protocols specific to fluid path.; Extraction conducted using protocols specific to fluid path devices; Extraction method for devices where fluids contact internal channels; Extraction method for devices where fluids contact channels; Specific extraction approach for fluid path devices; Extraction

material-mediated pyrogenicity

Testing for fever-inducing substances.

guinea pig maximization sensitization

Specific sensitization testing method.

MEM Elution

Specific cytotoxicity testing method.

biocompatibility testing

Testing to evaluate the biological response to medical devices.

Clinical Concepts

4

Cytotoxicity

endpoints should be addressed in your biocompatibility evaluation

adverse clinical findings

Observations during animal testing requiring rationale; Reporting of animal deaths or clinical findings; Observations such as animal deaths or body weight decrease; Observations of negative health effects in test animals

Acute Systemic Toxicity

Biocompatibility endpoint identified for testing

Hemolysis

Indirectly leads to increases in micronuclei by inducing erythropoiesis.

Standards & References

External Standards

4

USP 151

Standard for Pyrogen Test; Standard for pyrogen test

ASTM F756

Standard Practice for Assessment of Hemolytic Properties of Materials; Direct and Indirect Hemolysis

ASTM F720

Guinea Pig Maximization Test; Guinea pig maximization sensitization

USP <151>

Pyrogen Test; Material-Mediated Pyrogenicity

Specifications

2

Acceptance criteria

Metrics established by developers for each test element.

SC5b-9 Protein Concentration

Results measured in ng/mL

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements

4

Misbranded under section 502(o)

3

Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints

3

Adulterated under section 501(f)(1)(B)

3

Failure to establish and maintain procedures for implementing corrective and preventive actions

2

Failure to establish and maintain procedures for CAPA

2

Unapproved Device Violations

2

Failure to establish and maintain procedures to control the design of the device

2

Failure to establish and maintain adequate procedures to control the design of the device

2

Failure to adequately establish procedures for design controls

1

Biocompatibility Testing of Medical Devices - Standards Specific Information for the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program: Guidance for Industry, Accreditation Bodies, Testing Laboratories, and Food and Drug Administration Staff