Where Does IVIG Come From?

Have you ever wondered how your IVIG is made?

The "IG" in IVIG stands for immune globulins. These are antibodies. The "IV" stands for intravenous - infused into your body through your vein. In the case of GBS or CIDP, these infused antibodies are believed to counteract the effects of a patient's own "misbehaving" antibodies.

The WIG that you see infused into your arm is made from the plasma of thousands of donors. One plasma donation is needed to make 3 grams of WIG. So if you receive an infusion of 70g, roughly 23-24 donations had to be made.

Patients and treaters enjoy a relatively high comfort level that their IVIG product is safe. Behind the scenes, most of the effort and cost of plasma collection and manufacturing of plasma products is directed toward assuring that safety. The number one goal of plasma manufacturing facilities is safety. For manufacturers, safety means prevention of transmission of bacteria, viruses or other microorganisms. Prevention of viral transmission involves donor screening at plasma collection centers, and extensive testing of all plasma donations, and again on pooled plasma donations, and again during manufacturing for removal or inactivation of viruses. This process begins at plasma collection centers, and continues during manufacturing. The second very important goal is avoiding damage to the delicate IgG molecule, which is important for the efficacy and tolerability (comfort during and after infusion) of the product.

Plasma Collection Sites

Donors go to plasma collection centers that are located in communities nationwide.

At the plasma center donors are rigorously "screened". If there appears to be a chance that the individual could transmit a virus, and if the risk is deemed to be permanent, they are not permitted to donate and that name is added to the NDDR (National Donor Deferral Registry) - a list used by all plasma collection centers to make sure that people whose plasma has been determined to be unsuitable do not donate anywhere in the country. Those who are able to donate undergo a process called "plasmapheresis": The blood containing plasma is taken out of one arm and circulated through a machine that separates plasma from cells. Plasma is the yellow portion of the blood that contains proteins, such as antibodies, while the red portion contains blood cells. While people are only able to donate blood once every 6-8 weeks, plasma donations can be made up to two times a week, because the body replaces the plasma components quickly.

Once donated, each "unit" (one person's donation) of plasma is checked and labeled and frozen at the plasma center until it is shipped to the manufacturing facility. Plasma is only accepted from qualified, repeat donors. A first-time donor goes through the "applicant donor program". These donors receive a thorough medical screening and are checked against the NDDR. Plasma from a first time donor is held for 6 months; if the donor returns, it is processed. But if the donor does not return, it is destroyed as a precaution, because a second donation that tests negative for viruses provides additional assurance against viral transmission to the final product. Plasma from a repeat qualified donor is held for 60 days to allow for its retrieval if any test or post-donation information puts the donation in question before it is re-checked for viral contamination, and processed.

At the Manufacturing Facility

Acceptable plasma is thawed and "pooled", meaning thousands of plasma donations are mixed together. The pool is again rigorously tested for potential viral contaminants. Then the plasma goes through a manufacturing process during which the proteins needed for WIG are separated from the other plasma proteins. This purification process includes several viral removal and viral killing steps. Hundreds of Quality Control steps are performed throughout the manufacturing process to make sure the immune globulins are not subjected to variations that may harm the molecule. One example is temperature: Temperature must remain within a certain range, so temperature is documented periodically for each lot. A lot is released when it is determined that it has met the necessary specifications. A major goal is to make sure nothing happens that requires destruction of a "lot" (manufacturing batch). However, if a lot is ultimately destroyed, it is because of strict controls designed to insure patient safety.

Packaging and Distribution

When the vials (bottles) are filled. the MG heads to Packaging/Labeling for incubation (final viral inactivation step), cold storage, staging, inspection and ultimately packaging. Dedicated inspectors visually scrutinize each vial of IVIG for imperfections, and if anything looks suspicious, the vial is taken off the line. All labeling is proofed during development and then again after it is received in packaging. Vial labels and cartons are bar-coded to ensure proper tracking and identification by end user. Then, after imprints are verified a final time, cartons are weighed and boxed.

Preparing the plasma products for distribution is an equally important process. Final packaged products are stored in a temperature controlled warehouse where the shipping orders are processed. Products are packed in special cold chain shippers and/or temperature controlled trailers to control temperature and maintain the integrity of the product.

Information for Patients

These general steps are followed by all manufacturers of MG, and all plasma collection and manufacturing processes are continuously inspected - not only by the manufacturers, but also by regulators from the U.S. and other countries. However, there are differences in how each manufacturer prepares their product, and there can be slight variations from lot to lot even from the same manufacturer that are acceptable from a manufacturing or regulatory point of view.

Every patient is different and can have different responses to the same therapy. If you have a reaction, such as a headache, with a certain brand, you can ask to try a different brand or at least know to pre-medicate before using that brand. Treaters usually try to keep patients on the brand they have had success with, but shortages, reimbursement, change of infusion facility, and other factors may result in not being able to receive the brand you have used in the past. If this happens, and you have notes from previous infusions, you may be able to request a brand that works best for you.

It is a good idea to keep a logbook of your infusions. Whenever you receive MG, note in the logbook which brand is being used and the Lot #. Product recalls are issued by Lot #. If there should ever be a recall, manufacturers work with all appropriate regulatory authorities, distributors and other customers to ensure any affected product is returned to the company. It is also a good idea to get on the Patient Notification List of the PPTA, so that you receive notice of a recall if one is issued. Call 1-888-UPDATE -U, or check the Website: patientnotificationsystem.org/about.asp

The manufacturers' commitment to protecting the integrity of their products extends from the plasma centers to the manufacturing plant to the packaging line and into the product distribution channel to hundreds of hospitals and medical institutions, for the benefit of thousands of critical care patients all over the world. The entire system of checks and balances - of where the plasma comes from and where it goes - assures the safety and efficacy of the MG patients receive.