Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage: Guidance for Industry | Guideline Explorer

Description

This guidance document provides to you, sponsors of an investigational device exemption application (IDE) or an investigational new drug application (IND), recommendations about certain information that should be included in a submission describing a product intended to repair or replace knee cartilage. For the purposes of this document, a product intended to repair or replace knee cartilage, as with other cartilage repair or replacement products,1 may include a biologic, device, or combination product2 whose components would individually be regulated by the Center for Devices and Radiological Health (CDRH) or the Center for Biologics Evaluation and Research (CBER).3,4 This guidance finalizes the draft guidance of the same title dated July 2007.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

4

Combination Product

Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.

HCT/Ps

Human cells, tissues, or cellular or tissue-based products defined in 21 CFR Part 1271

Gene Therapy

A type of ATMP involving recombinant nucleic acids or viral vectors.

Cellular Product

Potency assay should measure attributes relevant to therapeutic effect; cellular products that have high inherent variability

Stakeholders

2

Institutional review board

approval required to commence a clinical study

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

6

IDE

Investigational Device Exemption submissions; Submission Documentation for Investigational Device Exemptions; Investigational Device Exemption submission recommendations

BLA

Biologics License Application

PMA

Premarket Approval Application

IND

Investigational New Drug submissions

Investigational New Drug Application

IND for treatment use; Regulatory submission required for clinical trials and expanded access.

Investigational Device Exemption

A medical device submission type (IDE).

Document Types

5

Chemistry, Manufacturing, and Controls

CMC section of the application where technical data for AMT suitability is submitted.

Case Report Forms (CRFs)

Used to ensure uniform reporting of adverse experiences

IKDC Knee Examination Form-2000

Form containing the ICRS evaluation

Animal Report

Documentation of nonclinical study results for submission

Mechanical Testing Report

Reports to be submitted for investigational products repairing knee cartilage

Attributes

2

significant risk devices

classification of investigational devices for articular cartilage repair

Durability

Demonstrating the stability of the IGA across generations

Technical Details

Testing Methods

10

Biocompatibility testing

Should be performed on the sterilized finished product simulating clinical use.

MRI

Imaging performed for DILI workup

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

Validated instrument for measurement of joint pain and function

IKDC Subjective Knee Evaluation Form-2000

Validated instrument for clinical measurement

Knee Injury and Osteoarthritis Outcome Score (KOOS)

Measure used to assess pain and physical function endpoints

Microfracture

Active concurrent control or comparator procedure

Mechanical Testing

conduct comprehensive mechanical testing to demonstrate that the device and its components can withstand mechanical stresses; conduct mechanical testing similar to the non-clinical testing on the explanted stents

Animal Studies

Testing to support premarket submissions

Magnetic Resonance Imaging

Imaging modality used for designing guides.

Histology

Used to provide qualitative analysis of tissues and confirm bone presence.

Processes

4

Sterilization

Required for contaminated equipment and media before disposal

Debridement

A multifactorial treatment requirement involving removal of devitalized tissue.; An adjunctive modality used in wound management.

Biocompatibility Testing

Testing to support safety data in marketing submissions.

Surgical Implantation

Route of product administration

Clinical Concepts

3

Articular Cartilage Lesion

The target condition for repair or replacement products

Adverse Experience

reporting for human drug and licensed biological products

Osteoarthritis

manifestations of obesity beyond excess adiposity

Identified Hazards

Hazards

2

Tumorigenicity

Risk associated with intended pharmacology or off-target effects

Systemic Toxicities

Potential for particle migration outside the articular space

Standards & References

External Standards

4

ICRS

Acceptable method for assessing cartilage lesions

International Cartilage Rating System

Acceptable way for determining subject eligibility by lesion size

ASTM F2451-05

Standard Guide for in vivo Assessment of Implantable Devices Intended to Repair or Regenerate Articular Cartilage.

ASTM F748-06

Standard Practice for Selecting Generic Biological Test Methods

Specifications

2

Complex Shear Modulus G*

Dynamic mechanical behavior assessment parameter

Aggregate Modulus

Static mechanical behavior assessment parameter

ICH References (1)

ICH E10

Choice of Control Group in Clinical Trials.

Related CFR Sections (6)

21CFR812.150§ 812.150 Reports.
(a) Investigator reports. An investigator shall prepare and submit the following complete, accurate, and timely reports:Read full regulation →
21CFR312.64§ 312.64 Investigator reports.
(a) Progress reports. The investigator shall furnish all reports to the sponsor of the drug who is responsible for collecting and evaluating the results obtained. The sponsor is required under § 312.33 to submit annual reports to FDA on the progress of the clinical investigations.Read full regulation →
21CFR812.25§ 812.25 Investigational plan.
The investigational plan shall include, in the following order:Read full regulation →
21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
21CFR56.103§ 56.103 Circumstances in which IRB review is required.
(a) Except as provided in §§ 56.104 and 56.105 , any clinical investigation which must meet the requirements for prior submission (as required in parts 312, 812, and 813) to the Food and Drug Administration shall not be initiated unless that investigation has been reviewed and approved by, and remaiRead full regulation →
21CFR812.27§ 812.27 Report of prior investigations.
(a) General. The report of prior investigations shall include reports of all prior clinical, animal, and laboratory testing of the device and shall be comprehensive and adequate to justify the proposed investigation.Read full regulation →

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to ensure that the investigation was conducted according to the investigational plan

21

Unapproved new drugs

10

Failure to submit an Investigational New Drug application (IND)

9

Unapproved new drug

7

Unlicensed biological products

6

Misbranded drug

6

Failure to validate aseptic processes

5

Failure to obtain informed consent

5

Failure to establish and maintain procedures for donor eligibility

4

Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination

4

Recent Cases

Related Warning Letters (10)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

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