Carticel ® 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). Carticel should be used only in conjunct...
For Autologous Implantation Only Patients in the Swedish series [ see Clinical Studies (14) ] received a wide range of cell doses per cm 2 of defect. Available data on 70 of 78 patients with femoral condyle defects showed a median dose of 1.6 million cells/cm 2 of defect. The middle 80% of these patients received from 0.64 million to 3.3 million cells/cm 2 . Each Carticel finished product vial contains approximate...
The Carticel 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 with...
www.fda.gov/medwatchCarticel® 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).
Carticel 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.
Carticel is not indicated for the treatment of cartilage damage associated with generalized osteoarthritis.
Carticel is not recommended for patients with total meniscectomy unless surgically reconstructed prior to or concurrent with Carticel implantation.
For Autologous Implantation Only
Patients in the Swedish series [see Clinical Studies (14) ] 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 Carticel finished product vial contains approximately 12 million cells. Vericel provides a single vial for each defect measuring ≤ 7 cm2. Two vials of Carticel 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 Carticel.
2.2.1 Handling Precautions
The Carticel product is intended solely for autologous use. Prior to Carticel 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 Carticel product [see Risk of Transmissible Infectious Diseases (5.2)].
Refer to the Indications and Usage (1) and Warnings and Precautions (5) Sections for additional considerations regarding the use of Carticel.
2.2.2 Preparation
NOTE:
The exterior of the Carticel 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.
Implantation of the Carticel product should be restricted to physicians who have completed Vericel's Surgeon Training Program.
Implantation of the Carticel® 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 Carticel Surgical Manual, Vericel document #65021 for instructions on the performance of these procedures.
2.3.1 Implantation
One vial of Carticel (autologous cultured chondrocytes) contains approximately 12 million cells.
Carticel 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 Carticel. Residual quantities of gentamicin up to 5 µg/mL are present in the Carticel 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 Carticel product.
Review of the data from the Study of the Treatment of Articular Repair (STAR) and the Registry Based Study (RBS) [see Clinical Trials Experience (6.1) ] as well as the Carticel worldwide experience (adverse reactions solicited through the Cartilage Repair Registry (CRR) and spontaneous reports) as of November 21, 1997 showed that the occurrence of a subsequent surgical procedure, primarily arthroscopic, following Carticel implantation is common. In the STAR study, 49% of patients underwent a subsequent surgical procedure, irrespective of relationship to Carticel (6.2). Symptoms leading to arthroscopic intervention included catching, locking, clicking or pain. Patients who develop clinical signs of tissue hypertrophy, including catching or clicking, should be evaluated and arthroscopy may be indicated for treatment or further assessment.
The Carticel product is intended solely for autologous use. Patients undergoing the surgical procedures associated with Carticel are not routinely tested for transmissible infectious diseases. Therefore, the cartilage biopsy and the Carticel product may carry the risk of transmitting infectious diseases to the health care provider handling these tissues. Accordingly, health care providers should employ universal precautions in handling the biopsy samples and the Carticel product.
The following conditions should be assessed and treated prior to or concurrent with implantation with Carticel:
The safety of the Carticel product is unknown in patients with malignancy in the area of cartilage biopsy or implant. The potential exists for in vitro expansion and subsequent implantation of malignant or dysplastic cells present in biopsy tissue. In addition, implantation of normal autologous chondrocytes could theoretically stimulate growth of malignant cells in the area of the implant, although there have been no reported incidents in humans or animals.
The Carticel product is shipped following a preliminary sterility test with a 48-hour incubation to determine absence of microbial growth. Final (14 day incubation) sterility test results are not available at the time of implantation.
Information on the safety of implanted autologous chondrocytes is derived from the Study of the Treatment of Articular Repair (STAR) [see Clinical Studies (14) ], 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.
The adverse reaction rates as well as the rate and type of subsequent surgical procedures from Carticel® 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 [see Study of the Treatment of Articular Repair (STAR) (14.2.2) ], patients who had experienced an inadequate response to a prior cartilage repair procedure underwent Carticel implantation to the index lesion. A total of 154 patients were implanted with Carticel; 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 Carticel, 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.
| Intervention | % of 154 Patients |
|---|---|
| Debridement of Cartilage Lesion* | 31% (47/154) |
| Lysis of Adhesions | 14% (21/154) |
| Synovectomy / Synovial Plica Excision | 12% (19/154) |
| Other Debridement† | 10% (16/154) |
| Chondroplasty | 6% (10/154) |
| Meniscectomy | 6% (10/154) |
| Loose Body Removal | 5% (7/154) |
| Microfracture – Index Lesion | 5% (7/154) |
| Scar Tissue Removal | 5% (7/154) |
| Release of Patellar Retinaculum | 4% (6/154) |
| Hardware Removal | 4% (6/154) |
| Microfracture – New Lesion | 4% (6/154) |
| Osteotomy | 3% (5/154) |
* Includes debridement of index lesion and other defects
† Includes debridement of other joint structures in addition to cartilage (e.g., patellar fat pad)
Lysis of adhesions was the most frequent surgical intervention performed in the first 6 months. After 6 months, cartilage debridement was the most frequently performed intervention. In the STAR study, 61% (46/76) of patients who required an SSP after Carticel did not meet failure criteria by either modified Cincinnati score or surgical criteria (e.g., graft delamination or surgical procedure violating the subchondral bone).
The most clinically significant interventions or findings involving the Carticel graft or periosteal patch are as follows: 3 Carticel grafts were completely removed and 1 was partially removed due to delamination. Partial delamination or fraying of the graft or periosteal patch was reported in 10 additional patients. Four (4) of these patients underwent reattachment/repair of the periosteal patch. Finally, a partially intact graft was found in 1 patient who was re-implanted. Detailed lists of interventions and findings that may have been associated with the graft or periosteal patch are presented in Tables 1 and 2, respectively.
Table 2 shows the serious adverse events (SAEs) that occurred in ≥ 5% of patients, regardless of relationship to study treatment.
| Serious Adverse Events | % of 154 Patients |
|---|---|
| Arthrofibrosis/Joint Adhesions | 16% (25/154) |
| Graft Overgrowth | 15% (23/154) |
| Chondromalacia or Chondrosis | 12% (18/154) |
| Cartilage Injury* | 11% (17/154) |
| Graft Complication† | 10% (15/154) |
| Meniscal Lesion | 8% (12/154) |
| Graft Delamination | 6% (9/154) |
| Osteoarthritis | 5% (7/154) |
Registry Based Study (RBS)
Data from a cohort of 97 Carticel® treated patients, who were retrospectively evaluated in the Registry Based Study [see Registry-Based Study (RBS) (14.2.1) ], showed that 39% (38/97) of patients had a SSP within 3 years of which 63% (24/38) were assessed as related to Carticel. Shaving or trimming (debridement) of overgrown tissue (hypertrophic) commonly relieved patients' symptoms. In the RBS, 67% (16/24) of patients who required arthroscopy after Carticel 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 Carticel.
| Symptoms or Surgical Findings (MedDRA preferred term) | % of 97 Patients |
|---|---|
| Graft Overgrowth | 10% (10/97) |
| Partial Graft Delamination | 8% (8/97) |
| Chondromalacia | 8% (8/97) |
| Arthrofibrosis/Joint Adhesions | 8% (8/97) |
| Arthralgia | 7% (7/97) |
| Synovitis | 6% (6/97) |
| Meniscal Lesion | 5% (5/97) |
| Loose Body | 5% (5/97) |
Swedish Series
Of 153 patients treated with autologous cultured chondrocyte implantation in the Swedish Series [see Clinical Studies (14) ], 22% (34/153) of patients experienced the adverse reactions presented in Table 4 below.
| Serious Adverse Reactions | % of 153 Patients |
|---|---|
| Tissue Hypertrophy | See below |
| Intra-articular Adhesions | 8% |
| Superficial Wound Infection | 3% |
| Hypertrophic Synovitis | 3% |
| Post-operative Hematoma | 2% |
| Adhesions of the Bursa Suprapatellaris | 2% |
| Hypertrophic Synovium | 1% |
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.
The following adverse reactions have been identified during post-approval use of Carticel®. 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 Carticel 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.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Carticel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Autologous cultured chondrocytes, the Carticel product, are derived from in vitro expansion of chondrocytes harvested from the patient's normal, femoral articular cartilage. Biopsies from a lesser-weight bearing area are the source of chondrocytes, which are isolated, expanded through cell culture, and implanted into articular cartilage defects beneath an autologous periosteal flap. Prior to final packaging, cell viability is assessed to be at least 80%.
Each single use container of autologous cultured chondrocytes has approximately 12 million cells aseptically processed and suspended in 0.4 mL of sterile, buffered Dulbecco's Modified Eagles Medium (DMEM). Both the biopsy transport media and the cell culture media contain gentamicin. Residual quantities of gentamicin up to 5 µg/mL may be present in the Carticel product.
Hyaline cartilage forms the articular surface of the femoral condyle. Studies have shown that implantation of autologous chondrocytes into the articular defect can result in the development of hyaline-like cartilage [see Clinical Studies (14) ].1,2,3,4,5 Normal hyaline cartilage consists of chondrocytes (≤ 5% total volume) and extracellular matrix (≥ 95% total volume). The matrix contains a variety of macromolecules, including type II collagen and proteoglycan. The structure of the matrix allows the hyaline cartilage to absorb shock and withstand shearing and compression forces. Normal hyaline cartilage also has an extremely low coefficient of friction at the articular surface. Damage to articular cartilage from acute or repetitive trauma often results in pain and disability. However, because hyaline cartilage is avascular, spontaneous healing of large defects is not believed to occur in humans.
A variety of surgical procedures have been used in attempts to promote repair of articular cartilage, and a few studies have evaluated the histology resulting from these interventions. Generally, procedures such as marrow stimulation techniques (MST) have been shown to produce fibrocartilage or hybrid mixtures of fibrocartilage and hyaline cartilage. Published data show that autologous chondrocyte implantation (ACI) is more likely than MST to result in hyaline-like cartilage at the repair site. 1,2,4,5 However, because of differences in study design, lesion size and concomitant patient conditions, these data are not sufficient to draw conclusions concerning the long-term correlation of histology and clinical outcomes.
No carcinogenicity or mutagenicity data are available for Carticel in animals or in humans. No studies on the effects of Carticel on fertility have been conducted.
Pre-Approval Studies
Bioactivity of autologous chondrocytes implanted under a periosteal patch was reported in the BLA for three rabbit studies6,7,8 of up to 52 weeks duration post-implant and one dog study9 of up to 18 months duration post-implant.
Rabbit Studies
Dog Study
Beyond histologic variability of the defect site, no adverse tissue reaction was identified in any animals in these studies.
Post-Approval Studies
Five additional large animal, post-approval studies were performed.
Goat Studies
Horse Study
While the defects in all animal models exhibited highly variable repair tissue quality (resulting in only moderate histologic scores) the best repairs with implanted chondrocytes produced hyaline-like cartilage characterized by matrix predominating in type II collagen and saffranin-O or toluidine blue staining proteoglycan. Chondrocyte labeling in one of the rabbit studies8 and in an independent study in goats by Dell'Accio et al10 demonstrated that the hyaline-like matrix in these defects was the product of the implanted autologous chondrocytes.
Clinical information regarding the use of autologous cultured chondrocytes was obtained from 2 open-label, observational studies consisting of a series of patients treated in Sweden and the Cartilage Repair Registry. Patients in the Swedish series received an autologous cultured chondrocyte product similar to Carticel®.
14.1.1 Swedish Series
The series consists of 153 patients who received autologous chondrocyte implantation for various defects of the knee. Patients presented with cartilage defects of the femoral condyle, patella, tibia, a combination of these, or osteochondritis dissecans, with or without comorbidity such as anterior cruciate ligament insufficiency requiring reconstruction.
Following autologous chondrocyte implantation, patients were followed for various durations. Clinical follow-up ranged from 1 week to 94 months; 86 patients had at least 18 months of follow-up. Most patients had arthroscopic evaluation; a subset had biopsy and histological evaluations. All patients were retrospectively classified as having one of three clinical outcomes: resumed all activities, some improvement, or no improvement. Clinical outcomes were also reported for patient subgroups including: 1) 40 patients with femoral condyle lesions, 2) 12 patients with osteochondritis dissecans lesions and 3) 22 patients who failed a prior debridement.
1) Clinical Outcome - Patients with Femoral Condyle Lesions
A total of 78 of 153 patients had femoral condyle lesions with or without co-morbidity. Patients had one or more defects ranging in size from < 1-20 cm2. Of the patients with femoral condyle lesions, 40 were evaluable after at least 18 months (median = 25; range = 18 to 94 months). Clinical outcomes for the 40 patients are summarized in Table 5.
| Defect | Resumed All Activities | Some Improvement | No Improvement | Total Patients |
|---|---|---|---|---|
| Femoral Condyle | 7 (29%) | 8 (33%) | 9 (38%) | 24 |
| Femoral Condyle plus other Non-Cartilage Repair | 4 (25%) | 9 (56%) | 3 (19%) | 16 |
| Total | 11 (28%) | 17 (42%) | 12 (30%) | 40 |
2) Clinical Outcome – Patients with Osteochondritis Dissecans Lesions
Of the 12 patients who received autologous cultured chondrocytes for treatment of an osteochondritis lesion, 6 of the 12 had "resumed all activities", 4 had "some improvement" and 2 had "no improvement" after the 18-month (median = 25; range = 18-94 months) follow-up period.
3) Clinical Outcome – Failed Earlier Procedures
Debridement of the cartilage defect is often performed along with administration of autologous cultured chondrocytes. To help differentiate the effects of the autologous cultured chondrocyte implantation procedure from those of debridement alone, an analysis was performed on 22 patients who had failed prior debridement and had a follow-up period after autologous cultured chondrocyte implantation which was at least as long as the time period to failure of their initial debridement. At the end of follow-up, 5 of the 22 patients had a functional outcome rating of "resumed all activities", 8 of the 22 patients had a rating of "some improvement" and 9 of the 22 patients had a rating of "no improvement." Thus, 13 of the 22 patients (59%) who had failed an earlier debridement had outcomes that were more favorable and durable following autologous cultured chondrocyte implantation than their previous debridement without cells.
Histological Outcome
Twenty-two (22) patients in the Swedish series had histological evaluation of biopsies from the implant site one or more years after their autologous chondrocyte implantation. Fifteen (15) of those patients had defects of the femoral condyle and 7 had defects of the patella. Six (6) of the 15 femoral condyle biopsies showed hyaline-like cartilage, 5 had a mixture of hyaline and fibrocartilage, and 4 had only fibrocartilage. Of the 6 biopsies with hyaline-like cartilage, 2 had minimal to no surface irregularities and 4 had some surface irregularities (e.g., fissures, fibrillations, etc.).
Arthroscopic Outcome
As an objective outcome evaluation, 86 of the 153 patients had a follow-up arthroscopy for investigational purposes at 18 months or more post-implantation. In some cases, the quality of repair observed at arthroscopy was considered to be supportive of the clinical or functional outcomes. A substantial number of patients were noted at arthroscopy to have tissue hypertrophy [see Adverse Reactions (6) ].
14.1.2 Cartilage Repair Registry
The Cartilage Repair Registry (CRR) was established upon the introduction of Carticel® into orthopedic practice in March of 1995. The CRR was designed to prospectively collect the clinical outcomes of Carticel and other cartilage repair treatments for chondral lesions in the knee. Clinical data were collected at baseline arthroscopy, implantation, intervals of 6 and 12 months, and annually thereafter; adverse reaction data were collected on an ongoing basis through CRR adverse reaction collection and spontaneous reporting. Inclusion in the CRR was based on a qualifying event that was defined as a knee arthroscopy in which a chondral lesion was identified and a cartilage biopsy was harvested. Participation in the CRR was voluntary, and not all patients biopsied or implanted were included. As of November 21, 1997, 891 patients had been implanted worldwide, and 644 of these patients were included in the CRR. Functional outcomes were based on responses to a modified version of the Cincinnati Knee Rating System.
Data from a subset of 191 US patients in the CRR as of December 31, 1996 who had undergone repair of lesions on the femoral condyle (medial, lateral or trochlea) were assessed to support licensure. Patients were between the ages of 15-57, 66% (126/191) were male, and 34% (64/191) were female and one patient's gender was not reported. Of these 191 patients, 38 had at least 12 months of follow-up. At study baseline, these 38 patients' mean rating of overall condition was 3.2, which is defined as fair to poor: limitations that affect activities of daily living-no sports possible. At 12 month follow-up, these patients reported an overall condition score of 6.4 defined as good: some limitation with sports but can participate if patient compensates. Although these patients were rated according to outcome measurements different from those used in the Swedish series, the results were consistent with the Swedish experience.
Two post-approval studies were conducted and completed as a condition of approval for Carticel®: the Registry Based Study (RBS) and the Study of the Treatment of Articular Repair (STAR).
14.2.1 Registry-Based Study (RBS)
The RBS was a retrospective analysis of data collected for a cohort of 97 US patients treated between March of 1995 and March of 1997. Of the 97 patients enrolled, 95% completed 1-year follow-up, 80% completed 2-year follow-up and 74% completed 3-year follow-up. Of these 97 patients, 44 were part of the subset of 191 US patients in the CRR described above. A limitation of this study is the lack of a control group. Patients included in this study had a prior non-Carticel cartilage repair procedure (e.g., debridement or marrow stimulation procedure) performed at the time of the index arthroscopy, subsequently failed this procedure and went on to receive Carticel. In the 5 years prior to the index arthroscopy for the study, this patient population had received prior knee surgeries to include: 47% (46/97) of patients had at least one debridement/lavage of a cartilage defect, 25% (24/97) of patients had a bone marrow stimulation procedure, 31% (30/97) had at least one diagnostic arthroscopy, 30% (29/97) had at least one meniscus repair/meniscectomy and 10% (10/97) of patients had a ligament repair/reconstruction performed on the treated knee.
Using a modified Cincinnati Knee Rating System at study baseline, this patient population had a mean overall condition score of 3.1 defined as fair to poor: limitations that affect activities of daily living-no sports possible. Patients included were between the ages of 16-56, 69% (67/97) were male and 31% (30/97) were female. For the type of defect, 62% (60/97) of the defects were acute while 37% (36/97) were chronic. Of the treated defects, 75% (73/97) were treated on the medial femoral condyle (MFC), 26% (25/97) on the lateral femoral condyle (LFC) and 19% (18/97) on the trochlea. Adverse reactions collected during this study are provided in Adverse Reactions (6).
14.2.2 Study of the Treatment of Articular Repair (STAR)
The STAR study was an open-label within patient comparison of a prior non-Carticel (index) procedure to implantation of Carticel for articular cartilage defects of the distal femur. All patients had experienced an inadequate response to a prior non-Carticel surgical treatment, defined as both: a) patient and surgeon agreement that the patient's symptoms/function required surgical re-treatment of the defect and b) the patient's rating of the overall condition of the knee was a score ≤ 5 using the Modified Cincinnati Knee Rating System. In this patient population, the median time to meet the failure criteria was 3.4 months for the prior non-Carticel procedure and 90% of patients failed within 10.3 months. Patients who met these criteria were treated with Carticel and assessed every 6 months for up to 4 years.
Treatment failure for Carticel was defined as any of the following: a) the patient underwent surgical retreatment that violated the subchondral bone or reimplantation with Carticel for the same index defect, b) complete delamination or removal of the graft, or c) the patient's rating of the overall condition of the knee using the Modified Cincinnati Knee Rating System failed to improve from the baseline knee score over 3 consecutive 6-month intervals.
A total of 154 patients were treated with Carticel. At the index surgery required for study entry, patients had one or more of the following interventions: 120 patients (78%) had debridement, 44 patients (29%) had microfracture, 18 (12%) had subchondral drilling, 10 (6%) had abrasion arthroplasty, and 7 (5%) had an osteochondral autograft. The mean lesion size was 4.6 (± 3.2, SD) cm2. Fifty patients (32%) had multiple lesions in the reference knee and 29 patients had Carticel implanted in more than one lesion. Lesions that were implanted were located on the medial femoral condyle in 109 patients, lateral femoral condyle in 32 patients and trochlea in 46 patients. Forty patients (26%) had lesions which involved osteochondritis dissecans (OCD).
Of the 154 patients treated with Carticel, 28 patients discontinued the study early. The numbers of patients completing the 24 and 48 month follow-up visits are 136 and 115, respectively. The majority of Carticel patients (N= 117) did not meet failure criteria during the study. By the end of the study, a total of 37 patients met the treatment failure criteria. Results for the 40 patients with OCD lesions were comparable to the total study population as 34 (85%) did not meet the failure criteria for the study and 6 (15%) failed treatment with Carticel. Table 6 illustrates, during each year of follow-up, the number of patients who failed Carticel by the surgical criteria along with the number of patients who failed by the Overall Modified Cincinnati scale criteria.
| 1 Year | 2 Years | 3 Years | 4 Years | Total | |
|---|---|---|---|---|---|
| Patients who Failed During the Interval | 14 | 11 | 11 | 1 | 37 |
| Surgery criteria | 0 | 5 | 5 | 1 | 11 |
| Overall Modified Cincinnati Scale criteria | 14 | 6 | 6 | 0 | 26 |
The Overall Modified Cincinnati mean baseline score for the patient population as a whole was 3.26, poor: significant limitations that affect activities of daily living, to fair: moderate limitations that affect activities of daily living, no sports possible. At 48 months, the mean score was 6.39, good: some limitations with sports but can participate/compensate. The improvement was statistically significant. Table 7 shows the improvement in the Overall Modified Cincinnati score over time.
| Visit | Baseline N=154 | Month 12 N=146 | Month 24 N=131 | Month 36 N=104 | Month 48 N=101 |
|---|---|---|---|---|---|
| Overall Modified Cincinnati Score*
Mean (SD) | 3.26 (1.02) | 5.58 (1.99) | 5.92 (2.08) | 5.87 (2.19) | 6.39 (2.31) |
* Scores are for patients who returned for follow-up. Patients who failed by score criteria are included and patients who failed by surgical criteria are excluded from the scores for timepoints after the failure criteria were met.
In addition to the change over time in activity level as measured with the Overall Modified Cincinnati Scale, there were similar and consistent changes in knee symptoms and function as measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS), a measure of knee-specific symptoms and function consisting of the following five subscales: pain, symptoms, sports and recreation, knee-related quality of life, and activities of daily living. At 12 months post-Carticel® implant, the mean improvement from baseline for the patient population as a whole in each subscale was as follows: pain 19 (N = 146), symptoms 15 (N = 147), sports and recreation 17 (N = 129), knee-related quality of life 18 (N = 147), and activities of daily living 18 (N = 145). At 48 months post-Carticel implant, the mean improvement from baseline was as follows: pain 24 (N = 100), symptoms 19 (N = 101), sports and recreation 31 (N = 86), knee-related quality of life 32 (N = 101), and activities of daily living 23 (N = 99).
Adverse reactions collected during this study are provided in Adverse Reactions (6).
The Carticel 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.
The Carticel® 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 Carticel Shipping Container or its Contents.
Do Not Sterilize.
If the Vial is Damaged or Sterility has been Compromised, Do Not Use.
Patients receiving autologous cultured chondrocytes for treatment of an articular cartilage defect should receive the following information and instructions.
Vericel Corporation
64 Sidney Street
Cambridge, MA 02139-4136 USA
Telephone: 800-453-6948 or 617-588-5566
Fax: 844-333-2847
Carticel® is a Registered Trademark of Vericel Corporation.
65001
Revision M
11/2015
Autologous
Cultured
Chondrocytes
Lot #: {LOT # - Ext}
Patient ID# : {PtID}
Expiry: {HH:MM} {Zn}
{DD MMM YY}
Vericel Corporation
Cambridge, MA 02139 Lic: 2010
Rx only
Label #: 63014.K 11/2015
Autologous Cultured Chondrocytes
Carticel®
FOR AUTOLOGOUS USE ONLY
NOT EVALUATED FOR INFECTIOUS SUBSTANCES
Vericel Corporation Patient ID #: {Patient ID}
{Patient Initials}
{Hospital Name}
Lot #:{LOT # - Ext}
Expiry: {HH:MM} {Zn} {DD MMM YY}
Store at room temperature. DO NOT FREEZE
({#})vial(s) approximately 12 million cells per vial in 0.4 mL DMEM
for implantation. No US Standard of Potency. NO PRESERVATIVES
Cells Expanded in Medium Containing 44 mcg/mL Gentamicin
See Insert for Complete Instructions and Dosing
Rx Only
Vericel Corporation
Cambridge, MA 02139 USA
Carticel® is a registered trademark of Vericel Corporation
Label #: 64014.J - 11/2015
License #: 2010
Autologous Cultured Chondrocytes
Carticel®
FOR AUTOLOGOUS USE ONLY
NOT EVALUATED FOR INFECTIOUS SUBSTANCES
Vericel Corporation Patient ID #: {Patient ID}
{First Mid Last}
{Hospital Name}
Lot #: {LOT #} - {Ext}
Expiry: {HH:MM}{Zn} {DDMMMYY}
Store at room temperature. DO NOT FREEZE
STORE CONTAINER IN SHIPPING BOX AS RECEIVED.
{#}vial(s) approximately 12 million cells per vial in 0.4 mL DMEM
for implantation. No US Standard of Potency. NO PRESERVATIVES
Cells Expanded in Medium Containing 44 mcg/mL Gentamicin
See Insert for Complete Instructions and Dosing
Rx Only
Vericel Corporation
Cambridge, MA 02139 USA
Carticel® is a registered trademark of Vericel Corporation
Label #: 64090.D 11/2015
License #: 2010
| Class | Version | Type | Effective |
|---|---|---|---|
| AUTOLOGOUS CULTURED CHONDROCYTES Pharmacologic Class Indexing | 2 | Indexing - Pharmacologic Class | 20181113 |
| NDC | Effective | Action | Document | Indexing SPL | Related label |
|---|---|---|---|---|---|
| 69866-1025-1 | 2020-01-31 | C162847 | 48780-1 | 9d75b9d0-c7c3-f424-e053-dadaa90a57ce | These highlights do not include all the information needed to use Carticel ® safely and effectively. See full prescribing information for Carticel. Carticel (autologous cultured chondrocytes) For Autologous Implantation Initial U.S. Approval: 1997 |
| Package NDC | Product | Description | Form | Quantity | Strength | SPL version |
|---|---|---|---|---|---|---|
| 69866-1025-1 | CARTICEL | 1 in 1 VIAL, GLASS | IMPLANT | 1 | 2 |
| NDC | Dashboard title | SPL version | Validation | Dashboard ZIP |
|---|---|---|---|---|
| 69866-1025 | CARTICEL (AUTOLOGOUS CULTURED CHONDROCYTES) IMPLANT [VERICEL CORPORATION] | 2 | Legacy NDC, 1 package rows | 20170207_096cf052-6510-412a-abf3-24e5a33ea316.zip |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 69866-1025-1 | EA - Each | 69866-1025 | b7c1c8c1-7511-4699-a313-c4ed38e28226 | 1 | 2017-03-06 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 69866-1025 | 69866-1025-1 |
| BLA | Proprietary name | Proper name | License type | Status | Latest source |
|---|---|---|---|---|---|
| 103661 | Carticel Sm Service | Autologous Cultured Chondrocytes | 351(a) | Disc | 2026-09-01 |
Every source-derived ingredient row is available through these pages.
| Name | UNII | Kind |
|---|---|---|
| autologous cultured chondrocytes | D5P3K3V822 | ACTIB |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| 45501f23-533e-4c7a-9203-2974d40c8a26 | 096cf052-6510-412a-abf3-24e5a33ea316 | 2017-02-06 | Warnings, Adverse reactions | 45501f23-533e-4c7a-9203-2974d40c8a26 096cf052-6510-412a-abf3-24e5a33ea316 |
Adverse event summaries are temporarily unavailable. Other product information remains available.