2.1 Dosage

For single patient use only.

GINTUIT is used as one application over a surgically created vascular wound bed in the oral cavity. The size of GINTUIT is adjusted for the size of the wound bed.

The safety and efficacy of repeat application(s) of GINTUIT have not been established.

2.2 Preparation

Preparation of the Surgical Site

Following local anesthesia, surgically create a vascular wound bed with viable wound edges and establish adequate hemostasis.

Preparation of GINTUIT

• Examine the sealed polybag for any leaks or evidence of damage or contamination.
• Verify the expiration date of GINTUIT. The product expires at 11:59 PM ET on the date of expiration.
• Verify that the product pH (6.8-7.7) is within the acceptable range, using the agarose gel medium pH Color Chart.
• Do not open the polybag until the surgical site has been prepared.
• Use GINTUIT within 15 minutes of opening the sealed polybag.

2.3 Application

• Always handle GINTUIT aseptically.
• Do not use GINTUIT if there is evidence of contamination, visible particulates, or pungent odor.
• GINTUIT, as supplied, is not a biohazardous material; however, follow your local (e.g., institutional or private practice) guidelines for disposal of any remaining GINTUIT.

1. Lift off the tray lid and place it on a surgical sterile field with the outer lid surface facing down. GINTUIT is packaged with the upper layer (containing keratinocytes that appear dull, with a matte finish) facing up and the lower layer (containing fibroblasts in extracellular matrix that appears glossy) facing down, resting on the polycarbonate base attached to the plastic insert (see Figure 1)
   
   
   
   Figure 1:
   GINTUIT, as supplied
   
   
2. Using a sterile blunt instrument, gently tease approximately 0.5 inches (1.3 centimeters) of GINTUIT away from the wall of the plastic insert (see Figure 2). Be careful not to perforate or lift the polycarbonate base beneath GINTUIT. The polycarbonate base should remain attached to the plastic insert.
   
   
   
   Figure 2:
   Teasing GINTUIT away from the wall of the plastic insert
   
   
3. With sterile gloved hands, insert either one index finger or a sterile blunt instrument under the released section of GINTUIT (see Figure 3). Use another finger or sterile blunt instrument to grasp GINTUIT in a second spot along the edge. Holding GINTUIT in two places, lift the entire GINTUIT out of the plastic insert using a smooth, even motion to prevent GINTUIT from bending and folding over onto itself.
   
   
   
   Figure 3:
   GINTUIT being lifted off the polycarbonate base
4. Place GINTUIT on the inner surface of the tray lid, maintaining the proper orientation (upper layer facing up) (see Figure 4). Handle GINTUIT by its edge to minimize damage.
   
   
   
   Figure 4:
   GINTUIT placed in the inner surface of the upper tray lid
   
   
5. Following removal of GINTUIT from the plastic insert, lift the plastic insert that contains the polycarbonate base from the bottom tray to ensure that this base is intact (see Figure 5a - intact polycarbonate base, and Figure 5b - torn polycarbonate base). Verify that pieces of this base are not removed and accidently applied to the patient.
   
   
   
   Figure 5:
   (a) Intact polycarbonate base and (b) torn polycarbonate base
   
   
6. Fold GINTUIT into a “z-fold” resulting in the upper layer exposed on the top side and the bottom layer exposed at the bottom side using either sterile gloved hands or sterile blunt instruments (see Figure 6).
   Note: Do not allow GINTUIT to fold or wrinkle upon itself. If needed, add sterile saline or another physiological salt solution to GINTUIT in the tray lid to facilitate folding. Do not use water.
   
   
   Figure 6:
   Folding GINTUIT
   
   
7. Trim GINTUIT with surgical scissors to the size needed for the surgical site. Use a sterile periodontal probe or other blunt instrument to stabilize the “z-folded” GINTUIT while trimming (see Figure 7).
   
   
   
   Figure 7:
   Trimming GINTUIT
   
   
8. Place the lower layer (i.e., fibroblast/extracellular matrix side) of GINTUIT in direct contact with the surgical site so that there are no pockets or wrinkled edges (see Figure 8). If needed, use saline to smooth wrinkles.
   
   
   
   Figure 8:
   Placement of GINTUIT on the surgical wound bed
   
   
9. Immobilize and attach GINTUIT to the surgical mucosal defect with sutures placed at the papillae and apically at each corner. If necessary, add a central suture at the apical margin or lateral margins. Use a crisscross (i.e., suspensory or sling) suture over GINTUIT to enhance stability and help maintain direct contact with the wound bed. GINTUIT must not move during mucosal or muscle traction. Tension may cause GINTUIT to tear.
10. If possible, to help protect GINTUIT, place an additional layer of GINTUIT, extending laterally beyond the defect margins over the “z-folded” GINTUIT, and suture at the four corners. The bottom side (i.e., fibroblast/collagen side) of this additional layer should be in contact with the previously applied “z-folded” GINTUIT.
11. Place a non-occlusive protective dressing over the treated site.

Hypersensitivity Reactions

There is a potential for hypersensitivity reactions to occur with GINTUIT.

Monitor for both early and later signs of hypersensitivity reaction following GINTUIT application. Evaluate and treat signs and symptoms of potential allergic reactions according to standard practice. If necessary, remove GINTUIT as part of the treatment for the allergic reaction.

5.2 Wound Infection

Monitor for signs and symptoms of wound infection. Signs of surgical site infection may include pain, edema, erythema, drainage, odor, warmth, or fever. The diagnosis of wound infection may be complicated by the white or yellow appearance of GINTUIT after it becomes hydrated with wound fluid.

5.3 Malignancies

The safety of this product for oral administration has not been evaluated beyond six months. The long-term potential for oral mucosal cancers to arise from, or in response to, this product is unknown.

5.4 Transmission of Infectious Diseases

Transmission of infectious diseases by known or unknown infectious agents may occur with GINTUIT.

GINTUIT contains cells derived from donated human newborn foreskin tissue. The foreskin donor’s mother was tested and found negative for human pathogens, including antibodies to human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), West Nile virus (WNV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and syphilis. GINTUIT cells are tested for human and animal viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma.

Product manufacture also includes reagents derived from animal materials, including bovine pituitary extract (BPE). All animal-derived reagents are tested for viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma before use. Bovine materials are sourced to minimize bovine spongiform encephalopathy (BSE), the cause of a rare fatal condition in humans called variant Creutzfeldt-Jakob disease (vCJD). vCJD has never been attributed to use of any medical product manufactured with BPE, but the theoretical possibility cannot be dismissed.

These measures do not totally eliminate the risk of transmitting these or other transmissible infectious diseases and disease agents. Report the occurrence of a transmitted infection to Organogenesis Inc. at 1-888-943-8235.

5.5 Sterility Testing

GINTUIT is shipped after passing primary test results from in-process microbial tests. A final sterility test is initiated prior to shipping, but the result will not be available for up to 14 days. If microbial contamination is detected after the product has been shipped, Organogenesis will notify health care providers and recommend appropriate actions.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of GINTUIT cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in clinical practice.

GINTUIT has been studied in two randomized, within-subject controlled (i.e., each subject received both GINTUIT and control treatment) clinical studies. The control treatment was a free gingival graft (FGG), using donor graft tissue from the subject’s palate. The duration of the studies was six months following GINTUIT application. Study One was a single-center study (n=25) to evaluate the safety and efficacy of GINTUIT in establishing a zone of attached gingiva. Study Two was a multicenter study (n=96) to evaluate the safety and efficacy of GINTUIT in establishing keratinized tissue (KT) in a similar study population.

Overall, 34% of subjects reported at least one adverse reaction. Table 1 lists all reported adverse reactions that occurred at an incidence of 1% or greater.

In Studies One and Two, local (occurring at the site of GINTUIT application) adverse reactions included gingival pain, gingival injury (due to inadvertent failure to remove a polycarbonate base from GINTUIT before application), and ulceration.

In another study (n=15), in which the placement of GINTUIT was under a mucosal flap, local (occurring at the site of GINTUIT application) adverse reactions included impaired healing and suture-related complications.

The safety of GINTUIT beyond six months was not evaluated in the clinical trials.

6.2 Postmarketing Experience

GINTUIT is manufactured using a similar process as Apligraf, an FDA-approved medical device. Localized allergic reaction, skin inflammation and erosion, skin blistering, localized wound infection, and cellulitis have been reported during post-approval use of Apligraf for the treatment of chronic cutaneous wounds. Because these reactions are reported voluntarily by a population of uncertain size, and because there are no controls, it is not possible to determine their frequency in the exposed population or establish a causal relationship to exposure to Apligraf. It is uncertain whether information obtained from the postmarketing safety database from use of Apligraf in chronic cutaneous wounds can be extrapolated to use of GINTUIT in the oral environment.

8.1 Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with GINTUIT. It is also unknown whether GINTUIT can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. GINTUIT should be used in a pregnant woman only if clearly needed.

8.4 Pediatric Use

The safety and efficacy of GINTUIT in infants and children have not been established.

8.5 Geriatric Use

Clinical studies of GINTUIT did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently than younger subjects.

12.1 Mechanism of Action

GINTUIT does not function as a tissue graft.

The mechanism of action by which GINTUIT increases keratinized tissue at the treated site has not been identified.