warnings and cautions
5 WARNINGS AND PRECAUTIONS Malignancy: The risk of malignancy in the area of cartilage biopsy or implant is unknown. Expansion of malignant or dysplastic cells present in biopsy tissue during manufacture and subsequent implantation may be possible. ( 5.1 ) Transmissible infectious diseases: Because patients undergoing procedures associated with MACI are not routinely tested for transmissible infectious diseases, cartilage biopsy and MACI implant may carry risk of transmitting infectious diseases. ( 5.2 ) Presurgical Comorbidities: Local inflammation or active infection in the bone, joint, and surrounding soft tissue, meniscal pathology, cruciate ligament instability, and misalignment should be assessed and treated prior to or concurrent with MACI implantation. ( 5.3 ) Product Sterility: Final sterility test results are not available at the time of shipping. ( 5.4 ) 5.1 Malignancy The safety of MACI used in patients with malignancy in the area of cartilage biopsy or implant is unknown. The potential exists for expansion of malignant or dysplastic cells present in biopsy tissue during manufacture and subsequent implantation. 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 such incidents reported in humans or animals. 5.2 Transmissible Infectious Diseases MACI is intended solely for autologous use. Patients undergoing the surgical procedures associated with MACI are not routinely tested for transmissible infectious diseases. Therefore, the cartilage biopsy and the MACI implant may carry the risk of transmitting infectious diseases to personnel handling these tissues. Accordingly, healthcare providers should employ universal precautions in handling the biopsy samples and the MACI product. Product manufacture includes reagents derived from animal materials. All animal-derived reagents are tested for viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma before use. Bovine materials are sourced to minimize the risk of transmitting a prion protein that causes bovine spongiform encephalopathy and may cause a rare fatal condition in humans called variant Creutzfeldt-Jakob disease. 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 Vericel Corporation at 1-800-453-6948. 5.3 Presurgical Assessment of Comorbidities To create a favorable environment for healing, assess and treat the following conditions prior to or concurrent with implantation with MACI: Local inflammation or active infection in the bone, joint, and surrounding soft tissue : patients should be deferred until complete recovery. Meniscal pathology : presence of an unstable or torn meniscus requires partial resection, repair, or replacement prior to or concurrent with MACI implantation. MACI is not recommended in patients with a total meniscectomy. Cruciate ligament instability : the joint should not possess excessive laxity, which may create excessive shear and rotational forces across the joint. Both anterior and posterior cruciate ligaments should be stable or undergo reconstruction prior to or concurrent with MACI implantation. Misalignment : the tibio-femoral joint should be properly aligned, and patella tracking should be normalized. Varus or valgus misalignment of the tibio-femoral joint and abnormal patella tracking may abnormally load joint surfaces and jeopardize the implant. Misalignment and patella tracking should be addressed with a corrective osteotomy or similar corrective procedure prior to or concurrent with MACI implantation. 5.4 Product Sterility MACI is shipped after passing preliminary test results from in-process microbial tests. A final sterility test is initiated prior to shipping, but the result will not be available prior to implantation. If microbial contamination is detected after the product has been shipped, Vericel will notify the healthcare provider(s) and recommend appropriate actions.