Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile: Guidance for Industry and Food and Drug Administration Staff

Description

Thisguidance documentupdates and clarifies the information regarding sterilization processes that we recommend sponsors include in 510(k)s for devices labeled as sterile. This guidance document also provides details about the pyrogenicity information that we recommend sponsors include in a 510(k) submission. For the current edition of the FDA-recognized standards referenced in this document, see the FDA Recognized Consensus Standards Database Web site athttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

3

Class I device

Device category that may be exempt from certain UDI requirements if GMP exempt.

Class II device

Device classification mentioned regarding novel sterilization methods

Single-use devices

Devices intended for one use only

Stakeholders

1

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

3

510(k)

Premarket notification submission type

PMA

Premarket Approval Application

HDE

Humanitarian Device Exemption submissions; Humanitarian Device Exemption pathway

Document Types

2

Device Master File

contains characterization of materials

validation protocol

the validation protocol; and the sterilization validation data

Attributes

2

Pyrogenicity

Premarket Submission Recommendations including Pyrogenicity

Sterility Assurance Level

Quality parameter that must remain unchanged for the policy

Technical Details

Testing Methods

6

Bacterial Endotoxins Test

Also known as the Limulus amebocyte lysate (LAL) test

seal strength testing

associated seal strength testing, to validate package integrity

real-time aging

simulated (and/or real-time) aging and associated seal strength testing

package test methods

description of the package test methods, but not package test data

half-cycle method

the method used to validate the sterilization cycle (e.g., the half-cycle method)

simulated distribution

FDA recommends that package test methods include simulated distribution

Processes

10

Sterilization

Required for contaminated equipment and media before disposal

Ethylene oxide

Established sterilization method; Established Category A sterilization method using a fixed, rigid chamber

Vaporized hydrogen peroxide

Established sterilization method; Established Category A sterilization method

Aseptic processing

High-risk manufacturing area requiring specific gowning; Access to aseptic processing areas during inspection

Dry heat

Established Category A sterilization method

Moist heat

Example of a sterilization method.

Radiation

Established Category A sterilization method including gamma or electron beam

Ozone

Established Category B sterilization method

Vaporized peracetic acid

Novel sterilization method

Novel Sterilization Methods

information identified in Section V.A above, the sponsor should provide the following information in a 510(k) for all novel sterilization methods

Identified Hazards

Hazards

2

Infection

Risk to human health from failure to assure sterility

Material-mediated pyrogens

chemicals leaching from device causing febrile reaction

Standards & References

External Standards

4

AAMI/ANSI/ISO 11607

Packaging for terminally sterilized medical devices, series of consensus standards

USP <1050>

Viral Safety Evaluation of Biotechnology products derived from cell lines of human or animal origin

USP <161>

Medical Devices-Bacterial Endotoxin and Pyrogen Tests

ANSI/AAMI ST72

Bacterial endotoxins – Test methods, routine monitoring, and alternatives

Related CFR Sections (5)

21CFR880.6860§ 880.6860 Ethylene oxide gas sterilizer.
(a) Identification. An ethylene gas sterilizer is a nonportable device intended for use by a health care provider that uses ethylene oxide (ETO) to sterilize medical products.Read full regulation →
21CFR880.6870§ 880.6870 Dry-heat sterilizer.
(a) Identification. A dry-heat sterilizer is a device that is intended for use by a health care provider to sterilize medical products by means of dry heat.Read full regulation →
21CFR880.6880§ 880.6880 Steam sterilizer.
(a) Identification. A steam sterilizer (autoclave) is a device that is intended for use by a health care provider to sterilize medical products by means of pressurized steam.Read full regulation →
21CFR880.6885§ 880.6885 Liquid chemical sterilants/high level disinfectants.
(a) Identification. A liquid chemical sterilant/high level disinfectant is a germicide that is intended for use as the terminal step in processing critical and semicritical medical devices prior to patient use. Critical devices make contact with normally sterile tissue or body spaces during use. SemRead full regulation →
21CFR876.1500§ 876.1500 Endoscope and accessories.
(a) Identification. An endoscope and accessories is a device used to provide access, illumination, and allow observation or manipulation of body cavities, hollow organs, and canals. The device consists of various rigid or flexible instruments that are inserted into body spaces and may include an optRead full regulation →

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

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

21

Misbranded under section 502(o)

19

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

10

Failure to adequately develop, maintain, and implement written MDR procedures

10

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

10

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

8

Unapproved Device Violations

8

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

8

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

8

Failure to develop, maintain, and implement written Medical Device Reporting (MDR) procedures

7