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:
- anemia
- thrombocytopenia
- bone disease
- hepatomegaly or splenomegaly
Important Safety Information
Approximately 15% of patients have developed IgG antibodies, and these patients have a higher risk of hypersensitivity reaction. Therefore periodic monitoring is suggested; caution should be exercised in patients with antibodies or prior symptoms of hypersensitivity. Symptoms suggestive of hypersensitivity occurred in 6.6% of patients, and include anaphylactoid reaction, pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis and hypotension.
Reactions related to Cerezyme administration have been reported in less than 15% of patients. Each of the following events occurred in less than 2% of the total patient population. Reported adverse events include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Adverse events associated with the route of administration include discomfort, pruritus, burning, swelling or sterile abscess at the site at the site of injection.
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).