1. Bone Graft Substitute
REGULATORY RATIONALE
Project # 102386
Date: November 24, 2010
Revision: 01
Author: Ujwal Parikh
______________ ______________ ______________
Project Manager Marketing Regulatory
Kazim Efendioglu Steve Tanenbaum Ujwal Parikh
______________ _______________ ______________
Pre-Clinical Clinical Quality
Asha Pullikal Shreelesh Gharat Daniel Carrino
Revision Change Date
New Original Document 11/24/2010

2. 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
MPW
Registered
1284048
Establishment Number:
Establishment Operations: Manufacturer

3. 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.
Claims
1. 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 Use
This 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.
Contraindications

4. The 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

5. 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 StemGro TM for
bone repair.
Clinical Studies

6. 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 Regis. Description
Class #
OP-1 Implant by 3 123.5680 OP-1 Implant is an osteoinductive and osteoconductive bone graft material
Stryker®. 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 3 342.6574 INFUSE® Bone Graft is recombinant human Bone Morphogenetic Protein-2
Graft by (rhBMP-2) applied to an absorbable collagen sponge (ACS) carrier. The
purpose of the protein, which occurs naturally in the body, is to stimulate
Medtronic®.
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 Patent Patent/Application Issue/Filing Date

7. Number
Porous bioceramics for bone scaffold
and method for manufacturing the 10/723,401 Nov. 26, 2003
same
Regeneration and augmentation of 09/840,284 June 26, 2002
bone using mesenchymal stem cells
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

8. • 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

9. • www.fda.gov
• www.iso.org
• https://www.infusebonegraft.com/
• www.stryker.com