Bone Graft Substitute

REGULATORY RATIONALE

Project # 102386

Date: November 24, 2010

Revision: 01

Author: Ujwal Parikh

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Project Manager Marketing Regulatory

Kazim Efendioglu Steve Tanenbaum Ujwal Parikh

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Pre-Clinical Clinical Quality

Asha Pullikal Shreelesh Gharat Daniel Carrino

Revision Change DateNew Original Document 11/24/2010

REGULATORY RATIONALE

NAME: UJWAL PARIKH

DATE : NOVEMBER 24,2010

Device Generic Name: StemGroTM

Device Trade Name: StemGroTM

Applicants Name Medical Design Device Corp.

Address: University Heights

Newark

NJ 07102

Classification Name: Filler, Recombinant Human Bone Morphogenetic Protein, Collagen Scaffold, Osteoinduction

Product Code: MPW

Registered Establishment Number:

1284048

Establishment Operations: Manufacturer

Description

StemGroTM is an orthopedic surgical implant for the treatment of bone damage caused due to

an injury or defect. StemGroTM consists of a Polycaprolectone- Hydroxyapatite (HA)/ -β

Tricalcium Phosphate (TCP) scaffold coated with allogeneic mesenchymal stem cells (MSC).

Once implanted in the body, the device stimulates natural bone healing by differentiating into

osteoblasts. Presence of allogeneic MSCs on a biocompatible scaffold makes it an

osteoconductive and osteoinductive bone graft material. Addition of recombinant human bone

morphogenic protein-2 increases bone healing by actively recruiting stem cells from

surrounding tissue and blood supply, initiating the bone formation cascade. 

Claims1. No immunological response due to the presence of allogeneic mesenchymal stem cells.

2. Enhances bone healing due to osteoinductive and osterconductive property of bone graft.

3. Enhanced biomechanical strength due to presence of polymer/ceramic based scaffold

4. Scaffold material easily biodegradable.

Indications for UseThis device has to be used under supervision of a healthcare professional only.

1. Treatment for distal long bone limb fractures with Gustilo-Anderson type I, II, III A or B without joint involvement.  

2. Can be used in addition to wound management along with an intermedullary nail for fracture stabilization.

3. An alternative to auto graft for treatment of open fractures.

ContraindicationsThe use of this device should be contraindicated in the following cases:

1. In the vicinity of a resected or extant tumor, in patients with any active malignancy, or in patients undergoing treatment for a malignancy

2. Patients who are skeletally immature (<18 years of age or no radiographic evidence of epiphyseal closure)

3. Pregnant women

4. Patients suffering from traumatic instability, metabolic & circumferential bone loss and inadequate neurovascular status.

5. Patients having medical history on iliac wing contraindicating bone marrow aspiration.

6. Patients with an active infection at the operative site.

7. Person with any metal implant or pacemakers

Governing Agency

The device is governed by Centre for Devices & Radiological Health.

The device requires Request for Designation as it is a combination product as per 21 CFR 3.2(e)

Classification of the Device

Class I

Class II

Class III X

Regulatory Pathway

Since it is a Class III Device, Pre-Market Approval (PMA) with Investigational Device

Exemption (IDE) should be submitted to the FDA. The device is a combination product and will

require Request for Designation. Pre-Clinical and Clinical studies should be carried out to

validate the claims, to prove substantial equivalence and to prove that the device is safe and

effective. Compliance with the general control provisions of the Federal Food, Drug & Cosmetic

Act (Act) is necessary.

Pre-clinical Studies

The safety of StemGroTM should be evaluated in accordance with the tests described in ISO

10993. Extensive biocompatibility and safety testing should be performed using StemGroTM,

including cytotoxicity, sensitization, genotoxicity, carcinogenicity and reproductive toxicity.

Additional studies, related to biomechanical testing, biodegradability, radiological observation

and histology should be performed using StemGroTM. The results of this extensive

biocompatibility and safety testing performed in a range of in vitro cell based studies and in

vivo animal studies should be properly documented to evaluate the safety of StemGroTM for

bone repair.

Clinical Studies

Under Investigational Device Exemptions, a randomized, prospective, controlled multicenter

study should be conducted to evaluate the ability of StemGroTM to safely heal distal long bone

limb fractures with Gustilo-Anderson type I, II, III A or B, without joint involvement. Study

entry should show that each patient failed to heal the conventional treatment. Three groups

will be created. First group will be given the conventional intermedullary rod treatment.

Second group will be given StemGroTM as a bone graft material for bone healing. Third group

will be given a combination of StemGroTM and IM rod. The results of this study will be analyzed

to evaluate the use of StemGroTM as a bone grafting material.

Registration Requirements (Device Listing)

Following devices with their registration number were approved by the FDA. These devices function similarly to our product.

Device Device Class

Regis. #

Description

OP-1 Implant by Stryker®.

3 123.5680 OP-1 Implant is an osteoinductive and osteoconductive bone graft material consisting of a combination of 3.3 mg of recombinant human BMP-7 (rhBMP-7) and 1 g of purified Type I bovine collagen, which is used as a carrier. The product is applied in the form of paste reconstituted with 2-3 cc of saline at the site of nonunion. OP-1 Implant is indicated for use as an alternative to auto graft in recalcitrant long bone nonunion where use of auto graft is unfeasible and alternative treatments have failed.

INFUSE® Bone Graft by Medtronic®.

3 342.6574 INFUSE® Bone Graft is recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) applied to an absorbable collagen sponge (ACS) carrier.  The purpose of the protein, which occurs naturally in the body, is to stimulate bone formation. INFUSE® Bone Graft is indicated for healing of open tibial fracture and as an alternative for auto graft.

Patent Determination

Name of the PatentPatent/Application

NumberIssue/Filing Date

Porous bioceramics for bone scaffold and method for manufacturing the same 

10/723,401 Nov. 26, 2003

Regeneration and augmentation of bone using mesenchymal stem cells

09/840,284 June 26, 2002

Compliance with the ACT

Registration and listing (21CFR Part 807) Labeling (21 CFR Part 801) Good Manufacturing Practice requirements as set forth in the quality systems (QS)

regulation (21 CFR Part 820) Electronic product radiation control provisions (Sections 53 1-542 of the Act) 21 CFR

1000-1050

ISO STANDARDS

ISO 10993-1:2009: Biological evaluation of medical devices -- Part 1: Evaluation and testing within a risk management process.

ISO 10993-2:2006: Biological evaluation of medical devices -- Part 2: Animal welfare requirements

ISO 10993-3:2003: Biological evaluation of medical devices -- Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity

ISO 10993-4:2002 provides general requirements for evaluating the interactions of medical devices with blood.

ISO 10993-5:2009 describes test methods to assess the in vitro cytotoxicity of medical devices

ISO 10993-6:2007 specifies test methods for the assessment of the local effects after implantation of biomaterials intended for use in medical devices.

ISO 15142-1:2003 specifies metallic medical devices used for the temporary intramedullary stabilization of long bones by surgical implantation, defining terms and giving requirements for intramedullary nails

ISO/TR 14283 provides fundamental principles for the design and manufacture of active or non-active implants in order to achieve the intended purpose.

ISO 14971:2007 specifies a process for a manufacturer to identify the hazards associated with medical devices.

ISO 13485:2003 specifies requirements for a quality management system where an organization needs to demonstrate its ability to provide medical devices and related services that consistently meet customer requirements and regulatory requirements applicable to medical devices and related services.

ISO 11607-2:2006 specifies the requirements for development and validation of processes for packaging medical devices that are terminally sterilized.

ISO 14155-1:2002 defines procedures for the conduct and performance of clinical investigations of medical devices.

References

www.fda.gov

www.iso.org

https://www.infusebonegraft.com/

www.stryker.com