Autologous Cultured Chondrocytes

FDA Drug Information • Also known as: Maci

Brand Names: Maci
Drug Class: Autologous Cultured Cell [EPC]
Route: INTRA-ARTICULAR
Dosage Form: IMPLANT
Product Type: CELLULAR THERAPY

Description

11 DESCRIPTION MACI, autologous cultured chondrocytes on porcine collagen membrane, is a cellular sheet that consists of autologous chondrocytes seeded on a 3 x 5 cm, resorbable porcine Type I/III collagen membrane, for implantation into cartilage defects of the knee. The active ingredients of MACI are the autologous cultured chondrocytes and porcine Type I/III collagen. The autologous chondrocytes are propagated in cell culture and are seeded on the collagen at a density of 500,000 to 1,000,000 cells per cm 2 . The final MACI implant contains at least 500,000 cells per cm 2 and does not contain any preservative. The product manufacture also uses reagents derived from animal materials. The resorbable, Type I/III, collagen membrane, which is a component of MACI, is porcine-derived. Fetal bovine serum is a component in the culture medium used to propagate the autologous chondrocytes; therefore, trace quantities of bovine-derived proteins may be present in MACI. These animal-derived reagents are tested for viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma before use. MACI may contain residual gentamicin because it is included during manufacture. Gentamicin is not included in the transport medium used to maintain product stability. Studies determined an average of 9.2 μg residual gentamicin per MACI implant. A final sterility test is initiated prior to shipping, but the result will not be available prior to implantation. Passing results from preliminary in-process microbial tests are required for release of MACI for shipping.

What Is Autologous Cultured Chondrocytes Used For?

1 INDICATIONS AND USAGE MACI ® (autologous cultured chondrocytes on porcine collagen membrane) is an autologous cellularized scaffold product indicated for the repair of single or multiple symptomatic, full-thickness cartilage defects of the knee with or without bone involvement in adults. Limitations of Use Effectiveness of MACI in joints other than the knee has not been established. Safety and effectiveness of MACI in patients over the age of 55 years have not been established. MACI ® is an autologous cellularized scaffold product indicated for the repair of symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement in adults. ( 1 ) Limitations of Use Effectiveness of MACI in joints other than the knee has not been established. Safety and effectiveness of MACI in patients over the age of 55 years have not been established.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For Autologous Implantation Only. Contact Vericel at 1-800-453-6948 or www.MACI.com regarding training materials for surgical implantation of MACI. For autologous implantation only. Contact Vericel at 1-800-453-6948 or www.MACI.com regarding training materials for surgical implantation of MACI. ( 2 ) The amount of MACI implanted depends on the size (surface area in cm 2 ) of the cartilage defect. ( 2.1 ) MACI should be cut to the size and shape of the defect and implanted with the cell-side down. ( 2.2 ) 2.1 Dosage The amount of MACI implanted depends on the size (surface area in cm 2 ) of the cartilage defect. The surgeon should cut the MACI implant to the size and shape of the defect, to ensure the damaged area is completely covered. MACI implant is for single-use. Multiple implants may be used if there is more than one defect. The size of MACI is adjusted for the size of each cartilage defect. 2.2 Preparation and Implantation Procedure Collection of Autologous Cartilage Biopsy The procedure may be performed arthroscopically. Using a ring curette or curved notchplasty gouge, harvest at least two (2) healthy full-thickness cartilage specimens from a lesser load-bearing area of the damaged knee, such as the lateral intercondylar notch, the superior lateral trochlear ridge, or the superior medial trochlear ridge. The specimens should measure approximately 5 x 8 mm each (200-300 mg total). The biopsy must be full-thickness and should include a small amount of subchondral bone, which will be removed prior to processing the biopsy. Some punctate bleeding may occur at the site of biopsy harvest. Using sterile technique, place the biopsy into transport medium bottle. Pre-Operative Preparation Confirm that the patient’s identity matches the patient identifiers on the MACI labels. Inspect the sealed MACI shipping box for any evidence of damage. Open the MACI shipping box and inspect the internal packaging for leaks (liquid) in the outer bag or self-seal pouch containing the bottle holding the MACI implant or for any evidence of damage or contamination. DO NOT USE if the patient identifiers do not match, or there are signs of leaking or damage to the packaging. Contact MACI representative immediately or call Vericel Customer Care at 1-800-453-6948. After inspection, keep MACI in its original packaging and store at room temperature until the surgical site has been prepared. Arthroscopic delivery is for lesions that are a maximum of 4 cm 2 in size and are accessible using an arthroscopic approach. Implantation Procedure Perform implantation procedure during arthrotomy or arthroscopy using sterile surgical techniques. Follow the implantation with an appropriate, physician-prescribed rehabilitation program [see Dosage and Administration ( 2.3 )]. NOTE: The MACI Surgical Implantation Kit may be used to assist with MACI knee surgery via arthrotomy. The MACI Arthroscopic Instruments may be used to assist with arthroscopic delivery....

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most frequently occurring adverse reactions (≥5%) reported for MACI were arthralgia, tendonitis, back pain, joint swelling, and joint effusion. Serious adverse reactions reported for MACI were arthralgia, cartilage injury, meniscus injury, treatment failure, and osteoarthritis. The most frequently occurring adverse reactions (≥5%) reported for MACI were arthralgia, tendonitis, back pain, joint swelling, and joint effusion. ( 6 ) Serious adverse reactions reported for MACI were arthralgia, cartilage injury, meniscus injury, treatment failure, and osteoarthritis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Vericel at 1-800-453-6948 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch for voluntary reporting of adverse reactions. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a product cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice. In a 2-year prospective, multicenter, randomized, open-label, parallel-group clinical trial, 144 patients, ages 18 to 54 years, were randomized to receive a 1-time treatment with MACI or microfracture (1:1, 72 patients in each treatment group). Demographic characteristics of patients in the trial were similar in both treatment groups. The majority of patients were male (62.5% MACI, 66.7% microfracture), and the mean ages were 34.8 (MACI) and 32.9 (microfracture) years. Overall, 70 patients in the MACI group and 67 patients in the microfracture group completed 2 years of follow-up. In addition, all 144 subjects from the 2-year clinical trial had the option to enroll in a 3-year follow-up study (extension study). Safety and efficacy assessments were performed at yearly scheduled visits. The demographic characteristics of patients (N = 128) enrolled in the extension study were similar in both treatment groups and consistent with the overall population of the 2-year clinical trial. The proportion of patients with at least one (1) subsequent surgical procedure (any surgical procedure performed on the treated knee joint, including arthroscopy, arthrotomy, or manipulation under anesthesia) in the 2 years following study treatment was comparable between treatment groups (8.3% in the MACI group and 9.7% in the microfracture group). Adverse reactions reported in ≥5% of patients in either treatment group in the 2-year clinical trial are provided in Table 1 . Table 1. Adverse Reactions in ≥5% of Patients in Any Treatment Group in the 2-Year Clinical Trial System Organ Class MACI n = 72 n (%) Microfracture n = 72 n (%) Musculoskeletal and Connective Tissue Disorders Arthralgia 37 (51.4) 46 (63.9) Back pain 8 (11.1) 7 (9.7) Joint swelling 7 (9.7) 4 (5.6) Joint effusion 5 (6.9) 4 (5.6) Injury, Poisoning and Procedural Complications Cartilage injury 3 (4.2) 9 (12.5) Ligament sprain 3 (4.2) 5 (6.9) Procedural pain 3 (4.2) 4 (5.6) General Disorders and Administration Site Conditions Treatment failure 1 (1.4) 4 (5.6) In the 3-year extension study, adverse reactions reported in ≥5% of patients were (MACI vs microfracture): arthralgia (46.2% vs 50.8%), tendonitis (6.2% vs 1.6%), back pain (4.6% vs 6.3%), osteoarthritis (4.6% vs 7.9%), joint effusion (3.1% vs 7.9%), cartilage injury (6.2% vs 15.9%), procedural pain (3.1% vs 7.9%), ligament sprain (1.5% vs 7.9%), and treatment failure (4.6% vs 7.9%). Serious adverse reactions reported in patients in either treatment group for integrated data across the 2-year clinical trial and the 3-year extension study are provided in Table 2 . Table 2. Serious Adverse Reactions in Patients in Any Treatment Group Across the 2-Year Clinical Trial and the 3-Year Extension Study System Organ Class MACI n = 72 n (%) Microfracture n = 72 n (%) Musculoskeletal and Connective Tissue Disorders Arthralgia 1 (1.4) 7 (9.7) Back pain 0 3 (4.2) Joint swelling 3 (4.2) 0 Joint...

Contraindications

4 CONTRAINDICATIONS MACI is contraindicated in patients with the following conditions: Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin. [see Description ( 11 )] Severe osteoarthritis of the knee (Kellgren-Lawrence grade 3 or 4). Inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders. Prior knee surgery (6 months), excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant. Inability to cooperate with a physician-prescribed post-surgical rehabilitation program [See Dosage and Administration ( 2.3 )]. Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin. ( 4 ) Severe osteoarthritis of the knee. ( 4 ) Inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders. ( 4 ) Prior knee surgery (within 6 months), excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant. ( 4 ) Inability to cooperate with a physician-prescribed post-surgical rehabilitation program. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary MACI implantation requires invasive surgical procedures; therefore use during pregnancy is not recommended. Limited clinical data on patients exposed to MACI during pregnancy are available. There are insufficient data with MACI use in pregnant women to inform a product-associated risk. Animal reproduction studies have not been conducted with MACI. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied A single patient order may contain one (1) or two (2) implants, each in its own bottle and shipper, depending on lesion size and number of lesions. MACI - One (1) Implant MACI, NDC69866-1030-5 (outer box), contains one (1) implant supplied ready for use as a single cellular sheet approximately 3 x 5 cm, in a sterile, sealed, translucent perfluoroalkoxy (PFA) resin bottle and cap. Each bottle contains one 3 x 5 cm implant with a 0.5-cm 2 section removed from the lower left-hand corner. MACI - Two (2) Implant MACI, NDC69866-1030-8 (outer box), contains two (2) implants supplied ready for use as cellular sheets approximately 3 x 5 cm, in a sterile, sealed, translucent perfluoroalkoxy (PFA) resin bottle and cap. Each bottle contains one 3 x 5 cm implant with a 0.5 cm 2 section removed from the lower left-hand corner. Each bottle is individually sealed in a clear self-seal pouch. Each self-seal pouch is placed into a 95kPa outer bag with absorbent material. These bags are enclosed in an outer box insulated with ambient temperature gel packs. Storage and Handling Store MACI at room temperature in its original packaging (outer box) until ready to use. DO NOT REFRIGERATE or FREEZE, or sterilize MACI. DO NOT USE if the bottle is damaged, has been compromised, or has leaked. Use MACI prior to 11:59 PM EST on the date of expiration printed on the package. Dispose of unused MACI or waste material as surgical biohazardous waste in accordance with local requirements.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.