How Lumizyme Is Produced

Lumizyme is produced using recombinant DNA technology, a process that allows scientists to alter the genetic make-up of an organism in order to produce human proteins such as enzymes.  This highly complex biomanufacturing process was developed after many years of research and testing. It takes place at Sanofi Genzyme facilities in three stages that last several months.

Stage 1: Growing Cells to Produce Human Enzyme

Lumizyme is a therapeutic protein.  Production begins by inserting the human gene that controls production of the GAA enzyme into CHO (Chinese hamster ovary) cells. Once the CHO cells have the gene, they will begin to manufacture the human GAA enzyme. The cells are kept under special conditions in large tanks called bioreactors. Each day, liquid is removed from the bioreactor, and the enzyme those cells have produced is collected for purification.

Geel plant
Production bioreactors like this one enable large-scale manufacturing of human proteins for ERT

Stage 2: Enzyme Purification

Lumizyme must meet very high standards for purity and safety. At Sanofi Genzyme, the enzyme is purified using a process called column chromatography, a method of separating and isolating the parts of a mixture to remove unwanted substances. As the enzyme moves through multiple chromatography columns, it becomes more purified.

Geel plant
Column filtering systems help eliminate unwanted compounds from the material that contains the enzyme

Stage 3: Filling and Finishing

After purification, the enzyme is put into sterile glass vials. After the vials are filled, they are placed into a freeze dryer for about 48 hours. In the freeze dryer, water evaporates off the enzyme and leaves a cake-like dry substance. In this form, the enzyme is more stable. Multiple tests are conducted through the manufacturing process to help ensure Lumizyme meets the highest standards. Each vial is inspected before it is released and made available for administering to patients.

Making Lumizyme is a complex process that takes several months and could only be accomplished after many years of development and testing.

INDICATION

LUMIZYME® (alglucosidase alfa) is an enzyme replacement therapy for patients with Pompe disease (acid α-glucosidase (GAA) deficiency).

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, and RISK OF CARDIORESPIRATORY FAILURE
  • If you or your child is taking Lumizyme, you should know that severe and potentially life-threatening allergic-type reactions known as anaphylaxis or severe hypersensitivity reactions, and other severe reactions related to the immune system may occur during and after Lumizyme treatment. Reactions may include, for example, kidney dysfunction, extreme difficulty breathing, shallow breathing, abnormal heart rate, low blood pressure, or throat tightness (including face, tongue and lip swelling) and skin lesions.
  • If you or your child experiences these severe reactions, you may require close observation during and after Lumizyme administration. You should discuss with your physician the signs and symptoms of anaphylaxis and hypersensitivity reactions and seek immediate medical care should they occur. Anaphylaxis or severe hypersensitivity reactions are potentially very dangerous. If such a reaction is severe enough, your doctor may decide to immediately discontinue the infusion and provide immediate medical care. Appropriate medical support measures may be administered when you are being infused with Lumizyme.
  • If your child has a current respiratory condition or illness and has compromised breathing or heart function due to Pompe disease, there may be risk of acute worsening of heart and/or lung function with Lumizyme due to the fluid of the infusion, and your doctor may decide that close observation during and after Lumizyme administration may be necessary.

WARNING AND PRECAUTIONS

Anaphylaxis and Hypersensitivity Reactions: Life-threatening anaphylaxis and hypersensitivity reactions have been observed in some patients during and after treatment with alglucosidase alfa. If such a reaction is severe enough, your doctor may decide to immediately discontinue the infusion and provide you with immediate medical care. Appropriate medical support and monitoring measures should be available during infusion.

Immune-Mediated Reactions: You or your child may be monitored for the development of systemic immune-mediated reactions while receiving Lumizyme. If these reactions occur, your doctor may discontinue the infusion and initiate appropriate medical treatment.

Risk of Acute Cardiorespiratory Failure: Infant Pompe patients with heart or breathing problems who are experiencing an acute respiratory condition may be at risk for increasing the seriousness of these problems as a result of Lumizyme administration due to the infusion fluid, and your child’s doctor may require additional monitoring for these infants.

Risk of Cardiac Arrhythmia and Sudden Cardiac Death during General Anesthesia for Central Venous Catheter Placement: Caution should be used when administering general anesthesia for the placement of a central venous catheter intended for Lumizyme infusion. Ventricular arrhythmias and slow heart rate resulting in cardiac arrest or death have been observed in infant Pompe patients with cardiac hypertrophy during general anesthesia for central venous catheter placement. Appropriate medical support and monitoring measures should be available during infusion.

Risk of Antibody Development: Since Lumizyme is a protein, it is the possible that patients receiving it develop antibodies. Some patients who develop high IgG antibody levels that last for a while may have reduced response to Lumizyme. Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter.

ADVERSE REACTIONS

The most frequently reported adverse reactions during Lumizyme studies in patients were allergy reactions and included: anaphylaxis, rash, fever, flushing/feeling hot, hives, headache, excessive sweating, nausea, cough, less oxygen in the blood, fast heart rate, rapid breathing, chest discomfort, dizziness, muscle twitching, agitation, bluish or purple skin, redness of skin, high blood pressure/increased blood pressure, facial paleness, chills, tremor, vomiting, fatigue, and muscle pain.

SPECIAL POPULATIONS

If you are pregnant, you should use Lumizyme only if your doctor has determined that its use outweighs any risks to your unborn child.

You may report side effects to the FDA at 1-800-FDA-1088.

Please see the Full Prescribing Information for complete details, including boxed WARNING.