Grafton™ and Grafton Plus™
M708348B351E Rev. D
Demineralized Bone Matrix (DBM)
2020-05-18
IMPORTANT INFORMATION ON THE GRAFTON™ AND GRAFTON PLUS™
DEMINERALIZED BONE MATRIX (DBM)
Note: not all parts may be available in each geography
READ BEFORE USE
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 the 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.
DBM allograft was prepared from human bone tissue recovered 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 U.S. 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*. This 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, single use containers. The lot
number, expiration date, product code, quantity (volume or size), and additional information are listed on the package label.
For US audiences only
Caution: Federal law (USA) restricts this product to sale by or on the order of a physician or dentist.
The device lifetime for Grafton™ Plus DBM, and 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 the current concepts and study design elements for process validation studies for the
removal and/or inactivation of viruses in the production of biopharmaceutical products recommended by the Food and Drug
Administration’s (FDA) Center for Biologics Evaluation and Research
were performed in 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 the risk of disease transmission via the use of Grafton™ DBM
and Grafton Plus™ DBM allografts beyond the protection provided by donor testing and screening procedures.
The process used to produce the non-demineralized cancellous bone chips in Grafton™ DBM Orthoblend does not afford the
same degree of viral inactivation as the process used to produce the DBM. However, the 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
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 the stability of the bony
structure. The voids or gaps may be surgically created defects or defects created by traumatic injury to the bone.
Grafton™ DBM (excluding the Orthoblend form) and GraftonPlus™ 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 the stability of the bony structure.
Grafton™ DBM and Grafton Plus™ DBM are absorbed/remodeled and replaced by host bone during the healing process.
Note: consider that Grafton™ DBM Crunch™ contains demineralized bone chips approximately 3 mm (±1 mm) 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, extensive tissue donor selection, and qualification processes
used in providing this tissue graft, transmission of 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, take precaution 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 Service recommendations and FDA regulations and guidance documents.