Medtronic T42090INT Instructions for Use

Grafton™ and Grafton Plus™

M708348B324E Rev. F

Demineralized Bone Matrix (DBM)

2020-06-03

IMPORTANT INFORMATION ON GRAFTON™ AND GRAFTON PLUS™
DEMINERALIZED BONE MATRIX (DBM)

Note: not all parts may be available in each geography.
This graft is derived from human tissue which was generously donated so others may benefit.
Each unit is intended for single patient, single use only.
Caution: restricted to use by a physician or dentist.
No additional sterilization step is to be performed.

DESCRIPTION

Grafton™ DBM and Grafton Plus™ DBM contain demineralized human bone tissue combined with an inert additive to yield a
demineralized bone matrix (DBM) allograft product having a particular physical form and/or handling property.

Grafton™ DBM Gel and Grafton Plus™ DBM Paste are produced from a powder form of DBM, while Grafton™ DBM Flex,
Putty, Matrix, Crunch™ and Orthoblend are produced from a fiber form of DBM. Grafton™ DBM Crunch also contains
demineralized bone chips/cubes, while Grafton™ DBM Orthoblend contains non-demineralized cancellous bone chips in
addition to DBM. Grafton™ DBM and Grafton Plus™ DBM are malleable and can be molded or cut into various sizes and
shapes according to the intended implant site.

This DBM allograft was prepared from human bone tissue recovered in the USA from a cadaveric donor using aseptic surgical
techniques and was microbiologically tested during recovery. The tissue was further processed under aseptic conditions and
treated with antibiotics (gentamicin), cleaned using 70% alcohol, washed with purified water, and sonicated. This allograft may
also have been processed with an additional surfactant. Subsequent demineralization of the bone tissue (using the D-MIN™
proprietary demineralization process) to produce the DBM in this product was performed so the resulting bone matrix has a
calcium content level that meets current American Association of Tissue Banks (AATB) standards. The demineralized bone
matrix (along with the cancellous bone chips for Grafton™ DBM Orthoblend) was combined with USP anhydrous glycerol
(Grafton™ DBM allografts) or a starch carrier (Grafton Plus™ DBM allografts) to form the final allograft product. The final
product in packaged form was tested for sterility according to procedures in the current US Pharmacopoeia, tested for
endotoxins using a qualified test method, and exported from the USA.

Grafton™ DBM and Grafton Plus™ DBM are demineralized bone allograft products that are osteoconductive as well as
osteoinductive in an athymic rat assay.

Grafton™ DBM and Grafton Plus™ DBM are prepared via a proprietary processing method of Medtronic validated to
consistently produce DBM that is osteoinductive in an athymic rat assay. Product and process consistency are confirmed via
ongoing testing of Grafton™ DBM and Grafton Plus™ DBM finished product for osteoinductivity in this validated athymic rat
assay using a five-point linear scale (0,1,2,3,4) to score bone formation at 28 days post implantation*. Bone forming activity
exhibited by Grafton™ DBM and Grafton Plus™ DBM in this athymic rat surrogate assay should not be interpreted as a
predictor of clinical performance.

*Edwards, J.T., PhD, Diegmann, M.H., MS, Scarborough, N.L., PhD.: Osteoinduction of Human Demineralized Bone:
Characterization in a Rat Model. Clinical Orthopaedics, December, 1998, Vol 357.

Grafton™ DBM and Grafton Plus™ DBM are packaged in ready-to-use form in single patient use containers. Lot number,
expiration date, product code, quantity (volume or size), and additional information are listed on the package label.

The device lifetime for Grafton Plus™ DBM, and Grafton™ DBM Orthoblend is two years in which it is expected to achieve its
performance and maintain its safety.

The device lifetime for Grafton™ DBM Flex, Grafton™ DBM Crunch, Grafton™ DBM Putty, Grafton™ DBM Gel, and Grafton™
DBM Matrix is three years in which it is expected to achieve its performance and maintain its safety.

VIRAL INACTIVATION PROCEDURES

DBM in Grafton™ DBM and Grafton Plus™ DBM is produced by a proprietary production process validated to inactivate viruses
including HIV-1, hepatitis B (duck hepatitis virus as model), hepatitis C (bovine diarrhea virus as model), CMV, and Polio.

Testing was performed according to current concepts and study design elements for process validation studies for removal

†

and/or inactivation of viruses in production of biopharmaceutical products recommended by the Food and Drug Administration’s
(FDA) Center for Biologics Evaluation and Research

certified conformity with Good Laboratory Practice for Nonclinical Laboratory Studies regulations stated in the Code of Federal
Regulations (21 CFR § 58).

These viral inactivation procedures were used to further reduce risk of disease transmission via the use of Grafton™ DBM and
Grafton Plus™ DBM allografts beyond protection provided by donor testing and screening procedures.

The process used to produce non-demineralized cancellous bone chips in Grafton™ DBM Orthoblend does not afford the same
degree of viral inactivation as the process used to produce DBM. However, risk of disease transmission with this tissue
component remains low due to multiple safeguards rigorously employed including donor screening, laboratory testing, and
material processing.

†

Data on file at Medtronic.

1, 2, 3

and the European community

4, 5, 6, 7

. All studies were performed in

INDICATIONS FOR USE

Grafton™ DBM and Grafton Plus™ DBM are intended for use as a bone graft extender, bone graft substitute, and bone void
filler in bony voids or gaps of the skeletal system (i.e. spine, pelvis, and extremities) not intrinsic to stability of the bony structure.
Voids or gaps may be surgically created defects or defects created by traumatic injury to bone.

Grafton™ DBM (excluding the Orthoblend form) and Grafton Plus™ DBM are also intended to be packed into bony voids or
gaps to fill and/or augment dental intraosseous, oral, and cranio-/maxillofacial defects. These defects may be surgically created
osseous defects or osseous defects created from traumatic injury to the bone, including periodontal/infrabony defects, alveolar
ridge augmentation (sinusotomy, osteotomy, cystectomy), dental extraction sites (ridge maintenance, implant preparation/
placement), sinus lifts, cystic defects, and/or craniofacial augmentation. Grafton™ DBM and Grafton Plus™ DBM may be used
alone in a manner comparable to autogenous bone chips or allograft bone particulate (demineralized freeze dried bone), or they
may be mixed with either allograft or autograft bone or bone marrow as a bone graft extender. Grafton™ DBM and Grafton
Plus™ DBM are indicated only for bony voids or gaps not intrinsic to stability of bony structure.

Grafton™ DBM and Grafton Plus™ DBM are absorbed/remodeled and replaced by host bone during the healing process.

Note: consider Grafton™ DBM Crunch contains demineralized bone chips approximately 3mm (±1mm) when determining the
appropriateness of this allograft for use in small defects.

CONTRAINDICATIONS

▪ Presence of infection at the transplantation site.
▪ Treatment of spinal insufficiency fractures.

CAUTION

This allograft may contain trace amounts of antibiotics (gentamicin), surfactant, and other processing solutions. Caution should
be exercised if the patient is allergic to these antibiotics or chemicals.

Grafton Plus™ DBM Paste contains starch. Therefore, caution should be exercised when using Grafton Plus™ DBM Paste in a
patient with a starch allergy and/or amylase deficiency.

PRECAUTIONS

Extensive donor blood serum testing, medical and social history screening procedures, and tissue microbiological testing were
used in the qualification of tissue donors. Despite viral inactivation and extensive tissue donor selection and qualification
processes used in providing this tissue graft, transmission of an infectious disease through the use of this tissue graft is still
possible. Bacterial infection at the graft site may also occur. Adverse outcomes potentially attributable to Grafton™ DBM or
Grafton Plus™ DBM must be reported promptly to Medtronic.

Adequate fixation should be used to stabilize the implant site during bone formation and healing in bony voids or gaps of the
skeletal system (i.e. spine, pelvis, and extremities).

If injecting Grafton™ DBM or Grafton Plus™ DBM into the defect site, precaution should be taken not to:

▪ Over-pressurize the delivery device, as this may lead to extrusion of the device beyond the site of its intended application

and damage to the surrounding tissues.

▪ Over-pressurize the defect site, as this may lead to fat embolization or embolization of the device material into the

bloodstream.

When used as a bone graft extender in bony voids or gaps of the skeletal system (i.e. spine, pelvis, and extremities), Grafton
Plus™ DBM Paste is intended for use only with autograft, not other allograft. Recommended ratios of Grafton Plus™ DBM
Paste to autograft as a bone graft extender are 1:1 or 2:1.

DONOR SCREENING AND TESTING

Prior to donation, the donor’s blood, tissues, and medical/social history were screened for medical conditions or disease
processes that would contraindicate the donation of tissues in accordance with current FDA regulations and standards
established by the AATB. The donor’s medical/social history was also screened for HIV, Hepatitis, and CJD/vCJD high risk
factors in accordance with current US Public Health Services recommendations and FDA regulations and guidance documents.

Testing of donor blood and tissue samples began at the site of recovery and continued into processing. Donor blood samples
taken at the time of recovery were tested for communicable disease by a laboratory registered with the FDA to perform donor
testing and certified to perform such testing on human specimens under the Clinical Laboratory Improvement Amendments of
1988 (CLIA) (42 U.S.C. 263a) and 42 CFR Part 493 using FDA approved, licensed, or cleared tests including:

▪ HBsAg (Hepatitis B Surface Antigen)
▪ HBc-IgM/IgG (Hepatitis B Total Core Antibody)
▪ HCV (Hepatitis C Antibody)
▪ HIV 1/2-Ab (Antibody to Human Immunodeficiency Virus Types 1 and 2)
▪ HTLV I/II (Human T-Lymphotropic Virus Types I and II)
▪ RPR/STS or Equivalent (Syphilis Detection)
▪ HIV 1 NAT (Human Immunodeficiency Virus type 1 nucleic acid amplification testing)
▪ HCV NAT (Hepatitis C virus nucleic acid amplification testing)

Results of all relevant communicable disease tests referenced were found to be negative or non-reactive.
In addition to the tests listed, other tests may have been performed including tests for HBV NAT (Hepatitis B virus NAT) and

WNV NAT (West Nile Virus NAT). NAT for HBV was performed for donors recovered after December 21, 2015 and in those
cases where the donor’s tissue is distributed to a country requiring such testing. If performed, results were negative or otherwise
acceptable for eligibility of donors of musculoskeletal tissues.

Communicable disease test results, together with the informed consent, medical and social history interview, physical
assessment, available medical records (to include previous medical history, laboratory test results, autopsy and coroner reports,
if performed), and information obtained from any source or records which may pertain to donor eligibility were evaluated. Based
on this evaluation, the donor met donor eligibility criteria current at the time of recovery. Donor eligibility criteria used to screen
this donor are in compliance with FDA regulations published in 21 CFR Part 1271 “Human Cells, Tissues, and Cellular and
Tissue-Based Products” and/or European Commission Directive 2006/17/EC including amendments and European national
transpositions when additional serological testing is required for deceased donors, as applicable.

Donor eligibility was determined by one of the following tissue banks:

American Tissue Services Foundation
Surprise, AZ 85378

Names and addresses of testing laboratories, the listing and interpretation of all required communicable disease tests, a listing
of documents reviewed as part of the relevant medical records, and the name of the person or establishment determining
eligibility of this human tissue are on file at Medtronic, Eatontown, NJ and are available upon request.

The final tissue allograft product was released by Medtronic based on the initial donor eligibility determination and on a post­processing review and determination that the product met all processing requirements and specifications.

This tissue allograft product was released for transplantation.

Community Tissue Services
Dayton, OH 45402

LifeNet Health
Virginia Beach, VA 23453

RTI Surgical, Inc.
Alachua, FL 32615

STERILITY

Grafton™ DBM and Grafton Plus™ DBM tissue allograft products were aseptically processed and tested for sterility, as
indicated by the package label. Tissue allografts labeled as “Aseptically Processed, Passes USP Sterility Tests” or “Sterile”
were aseptically processed and tested for sterility according to procedures in the current US Pharmacopeia. Medtronic may use
low dose gamma irradiation as an adjunct to aseptic processing to reduce bioburden. Grafton™ DBM and Grafton Plus™ DBM
package labels containing “Tissue Gamma Irradiated” indicate low dose (1.0–1.8Mrad) gamma irradiation was used as a means
of reducing the bioburden on the donor tissue.

When explanting and/or disposing of a device, be sure to avoid exposure to bodily substances such as blood, tissue, etc., as
contact could lead to infection or disease. Always wear and use proper equipment, taking special care with sharp objects and
needles. Follow your healthcare center’s policy regarding both the disposal of devices and any events of exposure.

TISSUE TRACKING

Federal (USA) regulations under 21 CFR 1271 establish requirements for tracking human tissue products. In accordance with
these regulations, the package label of each Grafton™ DBM and Grafton Plus™ DBM unit distributed by Medtronic bears a lot
number that serves as a distinct identification code recorded in Medtronic’s distribution records for tracking tissue to the
consignee or user/tissue transplant facility. This lot number should be recorded in the user/tissue transplant facility’s records
and in the tissue recipient’s medical record, along with the following:

1. Description of tissue

2. Lot number (donor ID)

3. Product code

4. Expiration date

5. Quantity implanted

If the tissue allograft is opened and not used, it should be disposed of properly or returned to Medtronic. Document the reason
for the tissue not being used.

For European Economic Area audience only: these tissue tracking records will be maintained for 30 years after clinical use. In
case product traceability to recipient is at risk, the customer will secure the transfer of the records to another entity (preferably a
tissue establishment or organ bank) to secure continued traceability. Medtronic BV will be informed of such a transfer of
records.

This traceability will be extended by the recording in the patient's records of the Single European Code, applied on the product
as of 29 April 2017, as required by COMMISSION DIRECTIVE (EU) 2015/565 and COMMISSION DIRECTIVE (EU) 2015/566.

6. Antibiotics used

7. Description of procedure

8. Date and time of procedure

9. Surgeon name

10. Any other pertinent information

INSTRUCTIONS FOR USE

Grafton™ DBM and Grafton Plus™ DBM were tested for sterility. Preparation of the bone graft bed is important for graft
incorporation and bone formation, as are other factors such as blood supply, source of marrow elements, loading, stability, and
absence of infection at the graft site. The volume of graft material used in each procedure is determined by the clinician.

Grafton™ DBM (Gel, Putty) and Grafton Plus™ DBM may be injected into the defect site (see Precautions and
Contraindications).

Before use, examine product package. Do not use if:

▪ Package materials or contents appear to be missing, tampered with, or damaged.
▪ The package label or identifying bar code is illegible or missing.
▪ The expiration date shown on the package label has passed.
▪ Any of the above conditions exist or are suspected.

Note: once a package seal is broken, the tissue should be either transplanted, if appropriate, or otherwise discarded. Used
allograft containers should be disposed of in accordance with recognized procedures for discarding medical waste material.

Opening Instructions

1. Peel open the outer pouch using proper sterile technique.

2. Pass sterile contents into sterile field.

3. For syringe type containers, remove and discard cap prior to use.

An Allograft Tissue Tracing Record is provided. Affix peel-off labels with tissue identification number to patient records and to
the Allograft Tissue Tracing Record. Fill out information and return as directed. Tissue utilization reports are necessary for
tracing tissue/recipient information in the unlikely event of suspected or actual transmission of disease and allowing appropriate
actions.

Grafton™ DBM Gel Preparation for Use

Keep the surgical site as dry as possible. Do not irrigate during or after placement of Grafton™ DBM Gel. Fluids such as water,
saline, or blood may alter consistency and handling. If Grafton™ DBM Gel is used in combination with autologous bone tissues,
other forms of allografts, or other bone grafting materials, remove excess fluids (including rehydration solution) from these graft
materials before the other grafts come into contact with Grafton™ DBM Gel.

Grafton™ DBM Putty Preparation for Use

Grafton™ DBM Putty requires no rehydration prior to use. A small amount of fluid such as blood, sterile water, or sterile saline
may be added to adjust consistency or handling. Also, simply kneading Grafton™ DBM Putty may enhance pliability and
cohesiveness.

Grafton™ DBM Flex Preparation for Use

Grafton™ DBM Flex may be rehydrated prior to use to attain porosity and full flexibility. Add sterile saline or blood until desired
consistency is achieved. Reconstituted product must be used within the time allocated for the surgical procedure.

Grafton™ DBM Crunch and Orthoblend Preparation for Use

Grafton™ DBM Crunch and Orthoblend require no hydration prior to use. A small amount of fluid such as bone marrow aspirate,
blood, sterile water, or sterile saline may be added to adjust consistency or handling. Also, simply kneading Grafton™ DBM
Crunch or Orthoblend may enhance pliability and cohesiveness.

Grafton™ DBM Matrix Preparation for Use

Grafton™ DBM Matrix may be rehydrated prior to use. A small amount of fluid such as blood, sterile water, or sterile saline may
be added to adjust consistency and handling.

Grafton Plus™ DBM Paste Preparation for Use

Grafton Plus™ DBM Paste requires no rehydration prior to use. A small amount of fluid such as blood, sterile water, or sterile
saline may be added to adjust consistency or handling. Also, simply kneading Grafton™ DBM Paste may enhance pliability and
cohesiveness.

Note: Grafton Plus™ DBM Paste will turn purple or black upon contact with iodine due to the presence of starch in the product.
This color change merely indicates the product has absorbed some iodine and does not present safety issues beyond those
associated with the iodine itself. If contact of the product with iodine occurs, the surgeon should use discretion regarding use of
the product just as with any other grafting material that would come into contact with iodine.

VISUAL INSPECTION

Visually inspect all sterile-barrier packaging before use. If the sterile barrier is damaged or the integrity has been compromised,
do not use the product. Contact Medtronic for return information.

Visually inspect the product before use. If the product is damaged, do not use the product. Contact Medtronic for return
information.

PACKAGING

Devices are supplied sterile. Packages for each of the components should be intact upon receipt. Once the seal on the sterile
package is broken, the product should not be re-sterilized. If a loaner set is used, all sets and components should be carefully
checked for completeness and to ensure there is no damage prior to use. Damaged packages or products should not be used,
and should be returned to Medtronic.

STORAGE

Refer to product package label for specific storage conditions. Do not freeze. It is the responsibility of the transplant facility or
clinician to maintain the tissue intended for transplantation in the appropriate recommended storage conditions prior to
transplant.

RETURNS

For any product returned to Medtronic, a Return Authorization Number is required from Medtronic prior to return. Refer to
Medtronic’s Return Policy.

For European Economic Area audience only: the customer will communicate serious adverse events (meaning any untoward
occurrence associated with the procurement, testing, processing, storage, and distribution of tissues and cells that might lead to
the transmission of communicable disease, to death or life-threatening, disabling or incapacitating conditions for patients or
which might result in, or prolong, hospitalization or morbidity) or serious adverse reactions (meaning an unintended response,
including communicable disease, in the donor or in the recipient associated with the procurement or human application of
tissues and cells that is fatal, life-threatening, disabling, incapacitating or which results in, or prolongs, hospitalization or
morbidity) within 1 day to Medtronic.

MRI INFORMATION

MR Safe
Grafton™ DBM and Grafton Plus™ DBM are MR Safe.
Grafton™ DBM and Grafton Plus™ DBM are nonconducting or nonmagnetic items which pose no known hazards in all MR

environments for magnetically induced displacement force and magnetically induced torque. In addition, Grafton™ DBM and
Grafton Plus™ DBM are not susceptible to heating due to RF (radio frequency) fields. As such, Grafton™ DBM and Grafton
Plus™ DBM can justifiably be labeled as MR Safe per ASTM F2503.

If Grafton™ and Grafton Plus™ DBM are used in connection with any device which is not MR Conditional, be advised this
combination was not tested in the MR environment and, therefore, higher heating and possible injury to the patient may occur.

PRODUCT COMPLAINTS

For product problems, contact Medtronic.
Patients in the European Union experiencing a serious incident in relation to the device should contact Medtronic and the

competent authority of the Member State in which they are established.

FURTHER INFORMATION

Recommended directions for use of this system (surgical operative techniques) are available at no charge upon request. If
further information is required, contact Medtronic.

To access the Summary of Safety and Clinical Performance for this device go to https://ec.europa.eu/tools/eudamed.

REFERENCES

Standards for Tissue Banking (current version), American Association of Tissue Banks, McLean, VA.
Current Policies and Procedures of Medtronic, Eatontown, N.J.
21CFR1271 titled “Human Cells, Tissues, and Cellular and Tissue-Based Products”
PHS Guidelines for Preventing Transmission of HIV through Transplantation of Human Tissue and Organs, MMWR 1994:43,

1-17.
PHS Guideline for Screening Donors of Blood, Plasma, Organs, Tissue and Semen for Evidence of Hepatitis B and Hepatitis C,

MMWR 1991:40, 1-17.
FDA Recommendations to Blood Establishments for “Deferral of Current and Recent Inmates of Correctional Institutions as

Donors of Whole Blood, Blood Components, Source Leukocytes, and Source Plasma,” 6/8/95.
FDA Recommendations to Blood Establishments for “Recommendations to Reduce the Possible Risk of Transmission of

Creutzfeldt-Jakob Disease By Blood and Blood products,” 4/2020.
European Directive 2004/23/EC On setting standards of quality and safety for the donation, procurement, testing, processing,

preservation, storage and distribution of human tissues and cells including amendments.
European Directive 2006/17/EC implementing Directive 2004/23/EC of the European Parliament and of the Council as regards

certain technical requirements for the donation, procurement and testing of human tissues and cells including amendments.
European Directive 2006/86/EC implementing directive 2004/23/EC of the European Parliament and of the Council as regards

traceability requirements, notification of serious adverse reactions and events and certain technical requirements for the coding,
processing, preservation, storage and distribution of human tissues and cells including amendments.

European Directive 2012/39/EU amending Directive 2006/17/EC as regards certain technical requirements for the testing of
human tissues and cells.

European Directive 2015/565 of 8 April 2015 amending Directive 2006/86/EC as regards certain technical requirements for the
coding of human tissues and cells.

European Directive 2015/566 of 8 April 2015 implementing Directive 2004/23/EC as regards the procedures for verifying the
equivalent standards of quality and safety of imported tissues and cells.

Relevant national transpositions of directives 2004/23/EC, 2006/17/EC and 2006/86/EC.

Notes

1. Center for Biologics Evaluation and Research, “Points to Consider in the Characterization of Cell Lines Used to Produce

Biologicals” (Food and Drug Administration) 1993.

2. Center for Biologics Evaluation and Research, “Points to Consider in the Manufacture and Testing of Monoclonal Antibody
Products for Human Use” (Food and Drug Administration) 1997.

3. Kozak RW. Viral Removal and Inactivation Issues for Biological Products. Proceedings of the 1991 Technical Program
Pharmaceutical and Cosmetic Industries Exposition and Conference. 1991: 253-260.

4. Committee for Proprietary Medicinal Products: Ad Hoc Working Party on Biotechnology/Pharmacy and Working Party on
Safety Medicines, Note for Guidance: “Validation of Virus Removal and Inactivation Procedures”, Biologicals 1991;
19-247-251.

5. Committee for Proprietary Medicinal Products: EEC Council Directive 89/381: “Medicinal Products Derived from Human
Plasma” (Revised Draft 1995).

6. Committee for Proprietary Medicinal Products: 1995 Revised CPMP Guidelines. Virus Validation Studies: The design,
contribution, and interpretation of studies validating the inactivation and removal of viruses (revised).

7. ICH Viral Safety Document Final September 1998: Viral Safety Evaluation of Biotechnology Products Derived from Cell
Lines of Human or Animal Origin.

©2020 Medtronic Sofamor Danek USA, Inc. All rights reserved.

DISTRIBUTED BY:

SpinalGraft™ Technologies LLC
4340 Swinnea Road, Suite 39
Memphis, TN 38118

EXPLANATION OF SYMBOLS

Medtronic Sofamor Danek USA, Inc.

1800 Pyramid Place
Memphis, TN 38132
Telephone: [phone] (USA)

901 396 3133 (Outside USA)

Fax: [phone]

15 °C

30 °C

CAUTION: Federal law (USA) restricts these devices to
sale by or on the order of a physician.

Temperature limit

Do not re-use

Manufacturer

Date of Manufacture

Catalogue number

Batch code

Sterilized using aseptic processing techniques

Use-by date

Consult instructions for use at this website.

Do not use if package is damaged

MR Safe

Medical device

Contains biological material of human origin

Single sterile barrier system

Double sterile barrier system

Single sterile barrier system with protective packaging
inside

Single sterile barrier system with protective packaging
outside