ZLB to launch nanofiltered IVIG
Viruses of the future are being targeted now at ZLB Bioplasma. Currently, ZLB purifies its intravenous immune globulin (IVIG) product, Carimune, through partitioning and virus inactivation. Viruses such as HIV, hepatitis C, and West Nile are removed or inactivated through these processes.
However, researchers at ZLB remember when blood products were contaminated with HIV and hepatitis C. They believe that as-yet-unknown viruses could escape current purification methods. Trying to head these future bugs off at the pass, ZLB has incorporated nano-filtration into the IVIG manufacturing process. So named because the pore size of the filter is rated at 50 nanometers, the nanofiltration step is the third and final step in purifying the IVIG. Already approved by the Food & Drug Administration, this new version of IVIG, Carimune NF, will soon hit the market.
ZLB's new IVIG product carries indications for primary immunodeficiency and immune thrombocytopenic purpura (ITP). It was approved after an FDA review of a phase III trial comparing Carimune NF with Carimune. The pharmacokinetics for both products were equivalent, said Craig Mendelsohn, M.D., J.D., medical director for ZLB, and "they did equally as well in efficacy."
Intravenous immune globulins are most commonly used to treat immune deficiencies. Immune globulins are protein molecules produced by the B lymphocytes in response to foreign microorganisms. These molecules are also called immunoglobulins or gamma globulins, but the most common term for them is antibodies. IVIG products contain immune globulins isolated from human plasma.
IVIG products have had a bit of a bumpy history. Problems with tampering and manufacturing deficiencies have led to shortages of the drug. Adverse effects have been a concern as well. Some patients have developed serious kidney complications after receiving IVIG, and others have suffered from thrombosis.
Some clinicians have suggested the sucrose contained in certain products may be to blame for the renal effects of IVIG. Sucrose is added to some IVIG preparations to prevent aggregation of the immune globulin molecules. As for the thrombosis problems, manufacturers have suggested that a too-rapid infusion rate may be the cause. Others believe the thrombosis events are more likely related to the osmolarity of the products.
Mendelsohn pointed out that some of the problems IVIG products have had are minimized with Carimune NF. The end product is a lyophilized form of IVIG, which can be reconstituted with either sterile water or sterile saline. "Certainly there are some patients that have problems with fluid overload," he said. By using sterile water to reconstitute Carimune NF, physicians can prevent adding extra sodium. "All compounds contribute to osmolality. This product allows the physician to manage osmolality." The powdered formulation also helps prevent tampering problems, he said.
While manufacturers may argue the differences between IVIG products are significant, all IVIGs are considered equally efficacious and safe when used appropriately, said Daniel Albrant, Pharm.D., president of Pharmacy Dynamics in Arlington, Va. As for ZLB's new product, he said, "Certainly you can agree that it's prudent to get the cleanest product that you can." Although the viral transmission risks associated with all IVIG products are minimal, he said, "there's a theoretical risk for transmission of virus particles."
However, Albrant feels this new filtration step might be stretching things a bit. "I think it's reasonable to be prudent, but they're going to the furthest extent of it."
If Carimune NF is more expensive than other IVIG products, Albrant doesn't expect he'll recommend it to any of his clients. "At least at this point, until there are head-to-head studies, all products work within the indications," he said. "There are no data that I know of right now comparing the safety of these products, nor do I truly believe that there are [differences in safety], except when it comes to marketing them."
"Certainly it's an additional step," said Martin Rosendale of nanofiltration. "But it's incorporated right into the [manufacturing] process." There is no decrease in yield or production of IVIG when adding the filtration step. Rosendale, ZLB's senior VP of sales and marketing, said that even though filtration does add a bit of a cost, the pricing of Carimune NF will be comparable to other products on the market,
"They're speculating that something's going to happen," said Albrant. That's not necessarily unreasonable, he added, but neither does it warrant extreme measures in the purification process. This may be true, but ZLB is banking on the past repeating itself. If and when a bug appears in the future that can bypass the conventional methods, the executives at ZLB believe their nanofiltration process may snag it. Who knows? They just might be right.
Jillene Magill-Lewis, R.Ph.
Jillene Lewis. New filtration process yields purified IVIG.
Apr. 21, 2003;147:HSE13.