The roadside signs what used to be Bayer HealthCare Biological Products Div., in Clayton, N.C., now proudly bear the name of Talecris Biotherapeutics.

As of mid-April, you had to look closely to see that the Talecris name is on plastic sheets stretched over the old signs.

On April 1, Bayer, the German health care giant, spun off its blood plasma business to a group of investors who formed Talecris. The new company will continue to make plasma-derived therapies used to treat a variety of rare disorders, including immune-system disorders and alpha-1 deficiencies. The people behind Talecris are hoping to leverage improvements in processing and efficiencies in packaging, especially secondary packaging, into success in a demanding industry.

And make no mistake: Plasma products are as demanding as medicine gets. The proteins in the plasma that make up antibodies–and, thus, are the target of plasma processing–are fragile and easily denatured. Most important from a packaging standpoint, the cold chain must be preserved all the way from production to use.

It isn’t easy

“The plasma industry as a whole isn’t an easy industry,” says Lacy McMahon, Talecris’ manager of communications. “It’s very complex and requires a lot of resources. It’s not like making standard pharmaceuticals like aspirin or ibuprofin.”

Talecris markets 10 plasma-derived medications. Its flagship is Gamunex, an intravenous immunoglobulin (IGIV) used mainly to treat two conditions:

* Humoral immunodeficiency disease, a congenital inability to make immunoglobulin, the protein that forms the basis for antibodies that fight disease;

* Idiopathic thrombocytopenic purpura, a malfunction of the immune system that leads it to attack the patient’s own red blood cells.

The Food and Drug Administration approved Gamunex in August 2003 as a replacement for a long-established IGIV called Gamimune. Gamunex was the result of an entirely new approach to the production of IGIVs, says Wytold Lebing, a research fellow with Talecris.

“With Gamunex, we started with a clean slate approach,” Lebing says. “We had Gamimune, which was a highly successful product, and we said, if we were going to start from scratch, how would we do it?”

The key difference between the two products, Lebing says, is in the way the protein that makes up the antibodies is handled. Under the Gamimune method, the protein was “precipitated out” by filtration–a process that could lead to damage. However, the process for Gamunex leaves the protein dissolved in the plasma. Another key improvement is the addition of caprylate, a substance that inactivates viruses for added safety. It’s an integral part of comprehensive pathogen safety that includes plasma screening.

Some of the packaging requirements for Gamunex and other Talecris products are shared by all forms of medication; others are unique to plasma-derived medicine.

As with all high-value medications, plasma products are liable to counterfeiting and tampering. This point was brought home in 2002 when Bayer HealthCare discovered that 13 vials of Gamimune had been diluted with saline. Although no adverse responses were reported, Bayer recalled two lots of Gamimune and announced the tampering to the FDA, the healthcare community and the press. The incident led Bayer to introduce tamper-evident seal tabs on all Gamimune cartons. A couple of months later, Bayer added tamper-evident shrink bands on all its vials.

The primary packaging for Gamunex, glass bottles to be used on IV stands, combines tamper evidence with practicality. A plastic band pulls away from the label to hang on the IV stand. Another portion of the label is a tracking tab that can be completely removed and attached to a patient’s medical chart.

Cold challenge

Gamunex and other Talecris products also face the ongoing challenge of cold-chain distribution. Plasma-based medications are extremely sensitive to heat. If they are exposed to temperatures outside specified ranges at any point in the distribution chain, it can compromise their efficacy.

Cold-chain distribution is especially daunting because of the huge variety of shipments Talecris must make. Talecris products go all around the globe, by truck, sea and airplane, in shipments ranging from a few vials to pallet loads. About one-third of all products shipped from the Clayton plant are shipped outside the U.S.

“For domestic sales, we needed to develop a range of solutions for customer orders ranging from one or two vials to full truckload shipments,” said Jim Bacon, Talecris’ director of global demand planning and customer operations.

Secondary packaging has to ensure that handling beyond the company’s control–often, beyond the ocean–won’t break the cold chain. In most cases, the allowable range of temperature is 2[degrees] to 25[degrees] C. (about 36[degrees] to 77[degrees] F.). Other distribution dynamics come into play: Product must be labeled in different languages and, in some cases, re-tested according to local regulations.