Presented to:Dr. M.P.Venkatesh,Asst. ProfessorRegulatory affairs groupDept. of PharmaceuticsJSSCP, Mysuru

Presented by:SURAJ P.S

1st M. Pharm ,

Regulatory affairs,JSSCP, Mysuru.

What is stent?

A stent is a tube or other device placed in the body to create a passagebetween two hollow spaces. There are a wide variety of stents used fordifferent purposes, from expandable coronary, vascular and biliarystents, to simple plastic stents used allow the flowof urine between kidney and bladder

Overview of cardiac stents ?

• Stents are small expandable tubes used to treat narrowed orweakened arteries in the body. In patients with coronary heartdisease, caused by the buildup of plaque, stents are used to opennarrowed arteries and help reduce symptoms such as chestpain (angina) or to help treat a heart attack.

• These stents are commonly called heart stents, but they're alsoreferred to as cardiac stents or coronary stents. Usually made ofmetal mesh.

• In the late 1970s, doctors began using balloon angioplasty to treatnarrowed coronary arteries. During this procedure, a very thin, long,balloon-tipped tube, called a catheter, is inserted into an artery ineither the groin or arm and is moved to the site of the blockage withhelp from an X-ray.

Cont……..

• Doctors developed small stents which could be mounted on the balloon section of the catheter and inserted into a blood vessel. During a stenting procedure, the stent expands when the balloon is inflated, locks into place, and forms a permanent scaffold to hold the coronary artery open even after the balloon is deflated and removed.

• In 1986, French researchers implanted the first stent into a human coronary artery.

• In 1994, the FDA approved the first heart stent for use in the U.S.

• First-generation stents were made of bare metal

• So doctors and companies began testing stents which were coated with drugs that interrupted the process of restenosis. These are called drug-eluting stents, which are now approved by the FDA.

Innovations in Heart Stents

• A stent with a covering that delivers an anti-restenosis drug over a period of several months and then essentially becomes a bare-metal stent

• A stent that is absorbed by the body and disappears after it has done its work

• A stent which uses a bio-engineered coating to quickly create a thin, all-natural layer inside the artery

• Other technologies under development include platinum-coated stainless steel stents, diamond carbon-coated stents, and gene therapy/antibody-coated stents

Regulation on Cardiac Stents

• These stents falls class III or HDE class

• These Devices are defined in 21 CFR 812.3,

• When an IDE application is required, a sponsor must not begin a clinical trial in humans in the United States until FDA has approved the application (21 CFR 812.20(a)(2), 812.42). Sponsors of such studies must comply with the following:

• IDE regulations (21 CFR 812)

• Regulations governing institutional review boards (IRB) (21 CFR 56)

• Informed consent (21 CFR 50).

• After FDA has approved a device, clinical studies conducted in accordance with the indications in the approved PMA, including clinical design validation studies conducted in accordance with the quality systems regulation

Cont………

• Such studies must be performed in conformance with the regulations governing institutional review boards (21 CFR Part 56) and informed consent (21 CFR Part 50).

Product Codes for Stents

Non-Clinical Engineering Tests

A. Material Characterization

1. Material Composition

2. Shape Memory and Super elasticity of Intravascular Stents

3. Stent Corrosion Resistance

B. Stent Dimensional and Functional Attributes

1. Dimensional Verification

2. Percent Surface Area

Percent Surface Area = 100 x (Area in Contact with Vessel ÷ Full Cylindrical Surface Area)

3. Foreshortening

4. Stent Integrity

5. Radial Stiffness and Radial Strength

6. Stress /Strain Analysis

7. Accelerated Durability Testing

8. Particulate Evaluation

C. Delivery System Dimensional and Functional Attributes

1. Dimensional Verification

2. Delivery, Deployment, and Retraction

3. Balloon Rated Burst Pressure (Balloon Expandable Stents Only)

4. Balloon Fatigue (Repeat Balloon Inflations)

5. Balloon Compliance (Stent Diameter vs. Balloon Pressure)

6. Tip Pull Test

7. Coating Integrity

Stent Delivery Sizes to Test

D. Shelf Life

To evaluate device functionality, we recommend that you repeat the following bench tests on aged devices:

• Stent Dimensional Verification

• Stent Foreshortening

• Radial Outward Force

• Particulate Evaluation

• Delivery System Dimensional Verification

• Delivery, Deployment, and Retraction

• Balloon Rated Burst Pressure

• Balloon Fatigue

• Balloon Compliance

• Balloon Inflation and Deflation Time

• Catheter Bond Strength

• Tip Pull Test

• Flexibility and Kink Test

• Torque Strength

• Coating Integrity

• Stent Securement for Unsheathed Stents

Labeling

A. Device Description

• available stent diameters and lengths

• guiding catheter/sheath compatibility

• deployment and RBPs

• percent stent free area.

B. Indications for Use

C. Contraindications

Contraindications describe situations in which the device should not be used because the risk of use clearly outweighs any possible benefit.

D. Warnings

• need for appropriate anticoagulation or antiplatelet therapy or both

• recommendation that when multiple stents are used, they should be of similar composition

• fact that long-term outcomes following repeat dilatation of endothelialized stents are unknown.

E. Precautions

F. Overview of Clinical Studies

G. Adverse Events

Humanitarian Device Exemption• An Humanitarian Use Device (HUD) is a device that is intended to benefit

patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year

• To obtain approval for an HUD, an humanitarian device exemption (HDE) application is submitted to FDA. An HDE is similar in both form and content to a premarket approval (PMA) application

• But is exempt from the effectiveness requirements of a PMA. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose.

• The application, however, must contain sufficient information for FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury

• The labeling for an HUD must state that the device is an humanitarian use device

and that, although the device is authorized by Federal Law, the effectiveness of the

device for the specific indication has not been demonstrated.

Designation of HUD status

A. Request for designation. Prior to submitting an HDE application, the applicant shall submit a request for HUD designation to FDA's Office of

Orphan Products Development.

1. A statement that the applicant requests HUD designation for a rare disease

2. name and address of the applicant

3. A description of the rare disease or condition for which the device is to be used, the proposed indication or indications for use of the device, and the reasons why such therapy is needed.

4. Documentation, with appended authoritative references, to demonstrate that the device is designed to treat or diagnose a disease or condition that affects or is manifested in fewer than 4,000 people in the United States per year.

Cont………

B. FDA action. Within 45 days of receipt of a request

1. Approve the request and notify the applicant

2. Return the request to the applicant pending further review upon submission of additional information.

3. Disapprove

I. There is insufficient evidence to support the estimate that the disease

II. FDA determines that, for a diagnostic device, 4,000 or more patients in the United States

c. Revocation of designation. FDA may revoke a HUD designation if the agency finds that

1. The request for designation contained an untrue statement of material fact or omitted material information

2. Based on the evidence available, the device is not eligible for HUD designation.

Using the FDA classification database, determine the classification of your device by researching “Predicate Devices” already registered in the US market.

Class III

Implement Quality Management System (QMS) which meets FDA Quality System Regulation (QSR) found in 21 CFR Part 820. This is also commonly known as FDA Good Manufacturing Practice (GMP).

Class III devices will likely require clinical studies.Get “Pre-Submission (Pre-Sub)” feedback from the FDA.

If clinical studies will be required, apply for an Investigational Device

Exemption (IDE). Develop clinical trial protocol and conduct studies.

Prepare and submit Premarket Approval (PMA) application. Pay PMA submission fee to FDA.

FDA issues PMA approval letter; posts online.

FDA conducts facility inspections of all major suppliers involved in the

design and production of your device. All parties must be compliant with

FDA QSR

At this time, you must be in full compliance with QSRs. Can issue a Form

483 for non-compliance

List your device and register your company using FURLS system on the

FDA website in accordance with 21 CFR Part 807; contract manufacturers

and sterilizers must also register and list. Specify your appointed US Agent.

Your FDA Establishment Registration and Listing must be renewed on a

yearly basis

If you have no local presence in the US, appoint an FDA US Agent representative as a local point of contact with the FDA.

You are now able to sell your device in the US. The FDA listing on their

website will serve as your authorization to commercialize your device in the

US. This authorization does not expire as long as certain types of changes

are not made, e.g., design, intended use.

Reference:

• http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm071863.htm

• http://www.fda.gov/CombinationProducts/JurisdictionalInformation/JurisdictionalUpdates/ucm106552.htm