The manufacture of Lumizyme® (alglucosidase alfa) employs recombinant DNA technology to produce the human GAA enzyme using Chinese hamster ovary (CHO) cells. Production begins with genetic modification of host CHO cells to express the human GAA gene. In brief, the human GAA gene is introduced into an expression vector (DNA construct), which is then inserted into CHO cells.
The genetically-modified CHO cells are then grown (replicated) in steps of increasing bioreactor volumes to achieve the desired cell density and conditions for optimal enzyme production and secretion into a liquid medium. After harvesting the culture medium, the recombinant human GAA enzyme is then isolated using a complex purification process, which includes multiple chromatography and filtration steps.
The liquid growth medium is sampled daily from the bioreactors to monitor cell growth and quality. After harvesting the culture medium, the GAA enzyme is isolated using a complex purification process, which includes multiple chromatography and filtration steps.
In order to ensure stability of the final product, it is sterile-filtered, filled into vials, and lyophilized into a powder. Following lyophilization, vials are ready for final quality-control testing, where each lot of Lumizyme undergoes an extensive series of tests to confirm consistent quality before release. To ensure that Lumizyme meets regulatory authority standards and specifications, it is rigorously tested during every stage of manufacturing.
LUMIZYME® (alglucosidase alfa) is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (GAA deficiency).
WARNING: Risk of anaphylaxis, hypersensitivity and immune-mediated reactions, and risk of cardiorespiratory failure
Anaphylaxis and Hypersensitivity Reactions: Life-threatening anaphylaxis and hypersensitivity reactions have been observed in some patients during and after treatment with alglucosidase alfa. If anaphylaxis or severe hypersensitivity reactions occur, immediately discontinue infusion and institute appropriate medical treatment. Appropriate medical support and monitoring measures should be available during infusion.
Immune-Mediated Reactions: Monitor patients for the development of systemic immune-mediated reactions involving skin and other organs.
Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness and compromised cardiac and/or respiratory function may be at risk of acute cardiorespiratory failure. Caution should be exercised when administering alglucosidase alfa to patients susceptible to fluid volume overload. Appropriate medical support and monitoring measures should be available during infusion and some patients may require longer observation times.
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 alglucosidase alfa infusion.
Risk of Antibody Development: As with all therapeutic proteins, there is potential for immunogenicity. There is some evidence to suggest that some patients who develop high and sustained IgG antibody titers may experience reduced clinical efficacy. Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter.
The most frequently reported adverse reactions (≥ 5%) in clinical trials were hypersensitivity reactions and included: anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia.
Pregnancy: Based on animal data, alglucosidase alfa may cause fetal harm.
Please see the Full Prescribing Information for complete details, including boxed WARNING.