Manufacturing

Genzyme is committed to leading the research, development, and manufacture of treatments for lysosomal storage disorders such as Gaucher disease.

Cerezyme is produced using advanced molecular biologic techniques based on recombinant DNA technology using a CHO (Chinese hamster ovary) mammalian expression system, the most widely used cell line for recombinant therapeutics. Genzyme has used the methodology extensively since 1994.

The advent of genetic engineering and recombinant human DNA technology allows for production of large-scale quantities of therapeutic proteins such as Cerezyme. Prior to the availability of this technology, Genzyme manufactured Ceredase® (alglucerase), a similar protein derived from human placentas. Recombinant technology has allowed for a more stable and reliable supply of the protein.

Sophisticated Techniques Help Ensure Reproducibility and Purity

The highly complex, multistep manufacturing process is designed to achieve consistency and reliability.

Cerezyme production begins with genetic modification of a host cell to produce β-glucocerebrosidase from human DNA. The CHO cell line was chosen for its well-characterized track record in the manufacture of biopharmaceuticals.

The human β-glucocerebrosidase gene is isolated, spliced into a bacterial plasmid, and inserted into the CHO host cell, which serves as a hospitable environment to manufacture the protein. In a bioreactor under carefully controlled conditions, the cells grow in a liquid medium of about 50 different nutrients such as sugar, amino acids, and salts. The enzyme is drawn off and collected for purification. To help ensure the product meets worldwide regulatory authority standards and specifications, testing takes place during every stage of the manufacturing process.

The purified enzyme is stabilized with excipients and undergoes double-sterile filtration before it is filled into vials under aseptic conditions. The vials are lyophilized (freeze-dried to remove oxygen and water) to enhance stability and storage. Each lot of Cerezyme undergoes an extensive series of quality control tests to confirm consistent quality before being released for patient use.

Indication & Usage

Cerezyme® (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions:

  1. anemia
  2. thrombocytopenia
  3. bone disease
  4. hepatomegaly or splenomegaly

Important Safety Information

Approximately 15% of patients have developed IgG antibodies to Cerezyme during the first year of therapy. Approximately 46% of patients with detectable IgG antibodies experienced symptoms of hypersensitivity, and these patients have a higher risk of hypersensitivity. It is suggested that patients be monitored periodically for IgG antibody formation during the first year of treatment.

Hypersensitivity has also been observed in patients without detectable IgG antibodies. Symptoms suggestive of hypersensitivity have been noted in approximately 6.6% of all patients, and anaphylactoid reactions in less than 1%. Treatment with Cerezyme should be approached with caution in patients who have exhibited hypersensitivity symptoms such as pruritus, flushing, urticarial, angioedema, chest discomfort, dyspnea, coughing, cyanosis, and hypotension. Pre-treatment with antihistamines and/or corticosteroids and a reduced rate of infusion may allow continued treatment in most patients.

In less than 1% of patients, pulmonary hypertension and pneumonia have been observed during treatment with Cerezyme. These are known complications of Gaucher disease regardless of treatment. Patients with respiratory symptoms in the absence of fever should be evaluated for the presence of pulmonary hypertension.

Approximately 13.8% of patients have experienced adverse events related to treatment with Cerezyme. Some of these are injection site reactions such as discomfort, pruritus, burning, swelling or sterile abscess at the site at the site of venipuncture. Additional adverse reactions that have been reported include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Transient peripheral edema has also been reported for this therapeutic class of drug.

To report suspected adverse reactions, contact Genzyme at 800-745-4447, option 2 or FDA at 800-FDA-1088 or http://www.fda.gov/Safety/MedWatch

Please see Full Prescribing Information (PDF).

Cerezyme is the only therapy with over 17 years of use in over 5,600 Gaucher patients, including children.