Osteoflex

Osteoflex® is indicated for the repair of symptomatic cartilage defects of the femoral condyle (medial, lateral or trochlea), caused by acute or repetitive trauma, in patients who have had an inadequate response to a prior arthroscopic or other surgical repair procedure (e.g., debridement, microfracture, drilling/abrasion arthroplasty, or osteochondral allograft/autograft).

Osteoflex should be used only in conjunction with debridement, placement of a periosteal flap and rehabilitation. The independent contributions of the autologous cultured chondrocytes and other components of the therapy to outcome are unknown.

Osteoflex is not indicated for the treatment of cartilage damage associated with generalized osteoarthritis.

Osteoflex is not recommended for patients with total meniscectomy unless surgically reconstructed prior to or concurrent with Osteoflex implantation.

Autologous cultured chondrocytes are used, as part of an overall program that includes knee surgery and special exercises, to help repair damaged knee cartilage. Cartilage is a type of tissue that joins together and helps support parts of the body. Autologous cultured chondrocytes are the patient's own cartilage cells. The cells are removed from the patient and sent to a laboratory, where they are processed to increase their number. The cells are then implanted (placed) in the damaged part of the knee. After implantation, the chondrocytes help form new, healthy cartilage.

For Autologous Implantation Only

Dosage

Patients in the Swedish series received a wide range of cell doses per cm² of defect. Available data on 70 of 78 patients with femoral condyle defects showed a median dose of 1.6 million cells/cm² of defect. The middle 80% of these patients received from 0.64 million to 3.3 million cells/cm².

Each Osteoflex finished product vial contains approximately 12 million cells. Vericel provides a single vial for each defect measuring ≤ 7 cm². Two vials of Osteoflex are provided for defects 7 to 14 cm², and three vials are provided for defects > 14 cm². This is based on Vericel's greater than 10 years of experience with Osteoflex.

Handling Precautions And Preparation

Handling Precautions

The Osteoflex product is intended solely for autologous use. Prior to Osteoflex implantation, match the patient name and ID number on the certificate of analysis to the patient's chart and the patient ID on the shipping box, transport cylinder and vial.

Health care providers should employ universal precautions in handling the biopsy samples and the Osteoflex product.

Refer to the Indications and Usage and Warnings and Precautions Sections for additional considerations regarding the use of Osteoflex.

Preparation

NOTE:

The exterior of the Osteoflex vial containing the cultured cells is NOT sterile. Follow strict sterile technique protocols.

When treating a defect that requires multiple vials of cells, resuspend, aspirate and inject one vial at a time.

1. Remove red plastic lid from vial. Wipe the vial surface and lid with alcohol.
2. Inspect vial contents for particulates, discoloration or turbidity. The cellular product appears as a yellowish clump in the bottom of the vial. Do not administer if contents appear turbid prior to cell suspension.
3. While holding vial in a vertical position, insert the needle of the intraspinal catheter into the vial. The needle must be positioned just above the fluid level. Slowly remove the inner needle from the catheter, leaving flexible tip behind. Attach a tuberculin syringe to catheter.
4. Lower the catheter tip into the media and position just above the cell pellet. Aspirate all the medium from the vial leaving only the cell pellet behind. Slowly expel medium back into the vial. This action will break the cell pellet and resuspend the cells in the medium.
5. Lower the catheter tip to the base of the vial and aspirate all contents into syringe, leaving the vial empty. Slowly inject the contents into the vial again. This will assure complete suspension of the cells. Repeat these steps as needed to ensure all cells are resuspended. Cell resuspension is complete when cell particles are no longer apparent, and the medium is a consistent, “cloudy” mixture. Aspirate all contents of vial into syringe. Always hold syringe vertical to keep an air pocket at the proximal end of syringe.

Administration

Implantation of the Osteoflex product should be restricted to physicians who have completed Vericel's Surgeon Training Program.

Implantation of the Osteoflex® product is performed during arthrotomy and requires both preparation of the defect bed and a periosteal flap to secure the implant. Complete hemostasis must be achieved prior to periosteal fixation and cell implantation. See the Osteoflex Surgical Manual, Vericel document #65021 for instructions on the performance of these procedures.

Implantation

1. Insert the catheter tip through the superior opening of the periosteal chamber at the site of the defect. Advance catheter to most inferior aspect of the defect.
2. Slowly inject a cell dose while moving the catheter tip from side to side and withdrawing the catheter proximally. This will ensure an even distribution of the cells throughout the defect.
3. Complete the implantation by closing the superior opening of the periosteum as instructed. See Osteoflex Surgical Manual, Vericel document #65021.

How supplied

Dosage Forms And Strengths

One vial of Osteoflex (autologous cultured chondrocytes) contains approximately 12 million cells.

The Osteoflex product, NDC 69866-1025-1, consists of viable, autologous cells packaged and labeled for implantation within specified time limits. Each vial contains approximately 12 million autologous cells for a single implantation procedure.

The shipping vials containing chondrocytes are accompanied by a technical data sheet with detailed specifications for the processed cells. The vial(s) of cells is placed within secondary packaging capable of maintaining the appropriate storage temperature and cell viability for up to 72 hours.

Storage And Handling

The Osteoflex® transport box should be held at room temperature and remain closed until the time of implantation to ensure proper storage conditions for the cells.

Do Not Refrigerate, Freeze, or Incubate the Osteoflex Shipping Container or its Contents.

Do Not Sterilize.

If the Vial is Damaged or Sterility has been Compromised, Do Not Use.

Vericel Corporation, 64 Sidney Street, Cambridge, MA 02139-4136 USA, Telephone: 800-453-6948 or 617-588-5566, Fax: 844-333-2847. Revised: Nov 2015

Osteoflex should not be used in patients with a known history of hypersensitivity to gentamicin, other aminoglycosides or materials of bovine origin.

Gentamicin is added to both the cartilage biopsy transport media and in the culture media used during the processing of Osteoflex. Residual quantities of gentamicin up to 5 µg/mL are present in the Osteoflex product.

Fetal bovine serum is a component in the culture medium used to propagate the autologous chondrocytes. Trace quantities of bovine-derived proteins may be present in the Osteoflex product.

Alcohol

May augment risk of GI bleeding.

Anticoagulants

May increase effect of anticoagulants because of decreased plasma protein binding and inhibition of platelet aggregation. May increase risk of gastric erosion and bleeding.

Beta-blockers

Antihypertensive effect may be decreased.

Cholestyramine

Effects of piroxicam may be decreased.

Lithium

May decrease lithium Cl.

Methotrexate

May increase methotrexate levels and toxicity.

Ritonivir

May increase concentrations and possibly the toxicity of piroxicam by inhibiting its metabolism.

Laboratory Test Interactions

May prolong bleeding time. May reversibly increase BUN and serum creatinine.

See also:
What are the possible side effects of Osteoflex?

Information on the safety of implanted autologous chondrocytes is derived from the Study of the Treatment of Articular Repair (STAR), the Cartilage Repair Registry, the Swedish Series, and post-marketing adverse event reporting.

The most common serious adverse events (> 5% of patients) derived from the STAR study include arthrofibrosis/ joint adhesion, graft overgrowth, chondromalacia or chondrosis, cartilage injury, graft complication, meniscal lesion and graft delamination. Only serious adverse events were collected in this study.

Clinical Trials Experience

The adverse reaction rates as well as the rate and type of subsequent surgical procedures from Osteoflex® studies of different designs cannot be directly compared amongst each other. Adverse reaction data from these studies do, however, provide a basis for identifying adverse reactions that may be related to product use and for estimating their frequency.

Study Of The Treatment Of Articular Repair (STAR)

In the STAR study, patients who had experienced an inadequate response to a prior cartilage repair procedure underwent Osteoflex implantation to the index lesion. A total of 154 patients were implanted with Osteoflex; 28 patients discontinued the study early. The numbers of patients completing the 24 and 48 month follow-up visits are 136 and 115, respectively. Mean patient age was 35 years at consent. The majority of patients were Caucasian (135; 88%) and male (106; 69%).

Seventy-six (76) (49% of 154) patients underwent 113 subsequent surgical procedures (SSPs) on the treated knee, irrespective of relationship to Osteoflex, during the 4 year follow-up. Of the 76 patients, 52 patients had 1 SSP, 15 patients had 2 SSPs, and 9 patients had 3 or more SSPs. Sixty-one (61) (80%) of the 76 patients who had an SSP underwent a procedure within the first 24 months after implantation. The majority of patients, 83% (63 of the 76), underwent an arthroscopy or manipulation under anesthesia only. Table 1 shows the interventions during SSPs in > 2% of patients.

Table 1: Interventions during Subsequent Surgical Procedures, Regardless of Relationship, in > 2% of Patients

Registry Based Study (RBS)

Data from a cohort of 97 Osteoflex® treated patients, who were retrospectively evaluated in the Registry Based Study, showed that 39% (38/97) of patients had a SSP within 3 years of which 63% (24/38) were assessed as related to Osteoflex. Shaving or trimming (debridement) of overgrown tissue (hypertrophic) commonly relieved patients' symptoms. In the RBS, 67% (16/24) of patients who required arthroscopy after Osteoflex had a good clinical benefit in terms of improved function and relief of symptoms. Table 3 shows the findings at surgery for the 38 patients who underwent a surgical procedure after Osteoflex.

Table 3: Most Frequent Findings (in ≥ 5% of Patients) at Subsequent Surgical Procedures in the Registry Based Study

Swedish Series

Of 153 patients treated with autologous cultured chondrocyte implantation in the Swedish Series, 22% (34/153) of patients experienced the adverse reactions presented in Table 4 below.

Table 4: Initial ACI Experience Swedish Series Serious Adverse Reactions (Occurring at a frequency of 1% or more)

About 1% of patients developed severe adhesions resulting in “frozen knee” and requiring lysis. Adverse reactions noted at a level of less than 1% included keloid-like scar, pannus formation, significant swelling of the joint, pain with post-operative fever, and hematoma following arthroscopy.

In this series, arthroscopy was scheduled to be undertaken at 18 months of follow-up, regardless of patient symptoms. Of the patients who had arthroscopy, 43% (37/86) had hypertrophic tissue.

Forty of the 85 patients had femoral condyle defects. Of these, 25% (10/40) of patients had some hypertrophic tissue noted at follow-up arthroscopy. Some patients had clinical symptoms that included painful crepitations or catching, and these symptoms generally resolved after arthroscopic resection of the hypertrophic tissue. Ten percent (10%) of patients with hypertrophy required additional treatment after hypertrophic tissue recurred following initial resection. Not all patients with tissue hypertrophy noted at arthroscopy were symptomatic.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Osteoflex®. Most of these reactions are reported voluntarily, and it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Furthermore, the reported frequency of spontaneous reports underestimates the true frequency of adverse reactions. As of July 31, 2006, approximately 12,500 patients have been implanted with Osteoflex and 559 patients have reported serious adverse reactions after treatment. The most frequently identified operative findings in these patients, in descending order of frequency, were graft overgrowth, graft delamination (partial or complete), arthrofibrosis, joint adhesions, meniscus lesion or tear, graft complications, chondromalacia, loose body in knee joint, and joint malalignment.