Medical Device Daily Washington Editor

WASHINGTON — Thanks to Starbucks and the makers of Mr. Coffee , caffeine junkies across the globe have forgotten by now the big splash made by freeze-dried coffee several decades ago, but the underlying process, known as lyophilization, has made another splash in modern medicine.

Based on a Greek term that translates roughly as “made solvent-loving,” lyophilization has made vaccines and large-molecule hormones such as human growth hormone cheaper to keep and ship and, hence, more available to the masses. Here at the 2007 edition of the annual meeting of the Society for Nuclear Medicine (Reston, Virginia), AnazaoHealth (Tampa, Florida) reported that it can take lyophilization a step farther with a June 12 patent from the U.S. Patent and Trademark Office for a process for stabilizing and lyophilizing radiopharmaceutical agents.

A number of biologics are lyophilized and reconstituted for the end user, such as human growth hormone (HGH), an example of which is Humatrope, made by Eli Lilly (Indianapolis). However, lyophilizing a radiopharmaceutical is much more complicated because in order to produce a stable and sufficiently potent radiopharmaceutical to last for any time at all on a hospital shelf, the process has to work much more quickly.

Robert McKenzie, senior VP, brachytherapy and nuclear products, said in a statement that the “novelty in the invention is centered on the rapid cooling and removal of ambient vapor, then ultra-cold removal of [remaining] ambient vapor when the potential of explosive liquid oxygen is eliminated.”

This process renders a product that “requires no further cold or refrigerated storage subsequent to stabilization, and can be delivered nationally overnight,” McKenzie said.

One of the more interesting aspects of radiopharmaceutical manufacturing is that it allows a company to produce a radiopharmaceutical for the individual patient rather than by large-batch production, making the company a compounding pharmacy rather than an FDA-regulated maker of a drug.

“I have [to deal with] every regulatory agency except FDA,” chairman/CEO Jacob Beckel told Medical Device Daily.

While not having to deal with the FDA may make him the envy of many firms, Beckel said Anazao has “a different set of hurdles,” including having to comply with Nuclear Regulatory Commission regulations.

Brooke Schum III, a partner in the practice of Daneker, McIntire, Schumm, Prince, Goldstein, Manning & Wildman (Baltimore), said that the speed of water removal is indeed the critical feature, a process that runs three to five hours for Anazao vs 12 hours for conventional lyophilization.

The radiopharmaceuticals the firm will process will be stable enough to store on site for several days, which means the patient can miss the appointment and the hospital does not have to eat the cost of the substance as long as the patient can reschedule shortly after the original appointment.

Because room-temperature storage is appropriate for these products, the end user does not need to heat the radiopharmaceutical, which cuts down on any damage to the tagged ligand in the substance. This process is effective for radiopharmaceuticals tagged for alpha, beta and gamma emitters, many of which the company’s patent references.

For on-site use, technicians need only reconstitute with a diluent that is appropriate in volume to obtain the desired concentration per each use.

Beckel said that this was not done before because “it was not needed.” Other firms that manufacture and ship radiopharmaceuticals are located near major centers because their products will decay quickly, which in the past has left hospitals in rural locations out of luck.

That has changed.

Beckel declined to project the company’s sales or market potential, but he did indicate that the prospects for this line of products are good.

“We’ve priced this at or below the cost of the conventional product,” he said, which when added to the shelf life, significantly lowers the cost to the end user.

“The lead product for us is MIBG,” or meta-iodo-benzyl-guanidine, Schumm said, which is indicated for detection of neuroblastomas, a cancer typically originating in the adrenal glands and most often diagnosed in children.

While the cancer is aggressively metastatic, any shut-down of the adrenal glands can quickly be fatal because the loss of cortisol production would mean that any inflammatory processes, whether due to disease or trauma, would go unchecked and result in a deadly state of inflammation of any affected organs.

The firm lyophilizes MIBG as isotopes bearing atomic numbers of 123 and 131, with the former serving as the detection agent for neuroblastomas and the latter acting as an agent of treatment. Both can be injected simultaneously, thus offering doctors a chance to locate and treat neuroblastomas in one procedure.

Schumm said that Anazao’s plan “is to license these substances to up-and-coming companies.”

While the first attempt to license the MIBG failed when the licensee opted to not exercise its license, the firm’s executives like the future for their products.

The exhibit floor at the 54th annual meeting of the Society of Nuclear Medicine (Reston, Virginia), offered a range of big machines with grand designs, but one of the more interesting offerings was found in the modest kiosk operated by the U.S. Department of Energy , which is still producing radioisotopes for clinical and research use. Much of this matter is extracted from weapons-grade radioactive substances left over from nuclear weapons research, the ultimate act of turning swords to plowshares.

The agency says that its stores of thorium 229 are increasing largely due to the normal decay of uranium 233, which the agency has had in storage at the Oak Ridge National Laboratory since the 1960s and 1970s. Some of the DOE inventory of thorium 229 is from direct extraction.

However, DOE has suspended its extraction of thorium 229 from the uranium pending a decision on how to dispose of the uranium inventory and wants industry to know that while these products are available now, it cannot hold on to the uranium forever.

Two by-products of thorium 229, actinium 225 and bismuth 213, can be used to treat ovarian cancer and acute myeloid leukemia, respectively.

Any interested parties are invited to contact the Oak Ridge National Laboratory.

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