Makers of “substitute” blood products have found no easy road to commercialization, and last week one of those companies found another roadblock in its way.

Under fire from an advocacy group criticizing a scheduled closed-door meeting this past Friday of an advisory panel, to discuss a trial for Hemopure, a blood substitute/oxygen therapeutic being developed by Biopure (Cambridge, Massachusetts), the FDA on the eve of that meeting abruptly cancelled it.

The agency said it would reschedule the meeting but did not provide an alternate date.

Biopure was on tap, along with the U.S. Navy, to discuss human testing of Hemopure in trauma subjects, a trial the FDA had put on hold over concerns about its safety, with a backstory of criticism concerning the ethics of the study.

The study is designed to treat patients in ambulances, a situation in which the patient is often unable to provide consent, or in a condition in which understanding of consent would be difficult. But the lack of informed consent is an ethical hurdle that has served as a magnet for criticism of Biopure and other companies relying on such a protocol.

Cancellation of the meeting appears as a response to a lawsuit filed by the advocacy group Public Citizen (Wash-ington), which argued that the meeting should be open to the public.

Biopure, the FDA and the Navy said the meeting was closed in order to protect trade secrets related to the product. Biopure said it had not signed a waiver enabling the meeting to be open, since that would have required additional time to prepare.

In its lawsuit, Public Citizen argued that the FDA had not followed proper protocol in establishing the meeting as closed-door.

It said the agency violated federal rules requiring that every meeting of an advisory committee shall be open to the public unless the head of the agency determines that a portion of the meeting may properly be closed, and that this determination is made in writing, with the reasons for closure explained. The group pointed to a Federal Register notice of the meeting that gave no description of the topics to be discussed.

Sidney Wolfe, director of Public Citizen's Health Research Group – which monitors the safety of medical devices, blood products and drugs – noted also that the FDA had previously rejected plans for the Navy's study in trauma patients. He said: “The public has a right to know what happens at this meeting, and I should have a right to attend and to participate in the discussion concerning the testing of this product.”

He further disputed BioPure's claim that the information to be discussed consisted primarily of trade secrets.

In its statement canceling the advisory meeting, the agency said that it had done so because of “significant public interest in the proposed study and the benefit of public discussion.” It said the rescheduled meeting would include “information [that] can be shared with the public.”

The statement further said: “The complexities involved in the development and evaluation of the safety and effectiveness of such products can raise many unique scientific issues.”

The meeting, the FDA said, was intended to include a discussion of “development plans for [Hemopure] and provide the FDA with additional independent expert input,” and that such meetings “are frequently closed to public participation because confidential commercial information is central to the discussions.”

“Given the level of public interest in this matter, the parties will work toward greater public involvement at this early stage,” the agency said. “The development of safe and effective treatments that could substitute for blood holds significant public health promise and could potentially save many lives.”

Public Citizen reacted to the cancellation by calling it “de facto admission that the meeting, had it been held in its closed format, would have violated the Federal Advisory Committee Act.”

The proposed trial is seen as an attempt, by the Navy, to find a blood substitute that is easier to store on ships than blood itself. It has proposed testing Hemopure in more than 900 patients – non-Navy personnel – around the country.

Another blood substitute developer that has run up against the lack-of-informed-consent barrier is Northfield Laboratories (Evanston, Illinois). That company has been the target of stories by the Wall Street Journal focusing on the waiver of consent using its Polyheme product in a trauma study and deaths in an earlier trial (Medical Device Daily, March 16, 2006), and drawing critical comments by Sen. Charles Grassley (R-Iowa) regarding what he termed “urgent ethical concerns.”

Northfield responded by citing its adherence to FDA regulations allowing a waiver of informed consent “when patients are in a life-threatening situation” and “when current therapy is unproven or unsatisfactory.” It acknowledged deaths in the earlier trial but said these were apparently the result of “fluid management issues” rather than the “pharmacologic effect” of Polyheme.

Last week, Biopure also felt compelled to defend itself against what it termed “imbalanced perspective” in recent WSJ articles, issuing a lengthy statement defending its protocol as “valid when there are patients at risk who, data suggest, may benefit from Hemopure.”

It explained that the trial could proceed only if the FDA lifted a “clinical hold” and “the Department of Defense and the institutional review boards of participating hospitals” gave their final authorization. It noted also that if the trial were allowed to go forward, trial details, including its risk and benefits “for the out-of-hospital treatment of trauma patients with acute blood loss would be made publicly available through a clinical trial web site and extensive community notification activities.”

Another problem Biopure has dealt with is charges by the Securities and Exchange Commission (SEC) that it attempted to pump up its stock price by claiming in a press statement that Hemopure no longer required tests from the FDA. The SEC charged that those statements implied the FDA gave the drug candidate positive reviews while it had actually asked for a hold on some clinical trials over safety concerns.

In March, the company agreed to an injunction against future violations and consented to retaining an independent consultant to review and make recommendations about its disclosure procedures (MDD, March 15, 2006).

In April, the SEC filed a civil action against Carl Rausch, former vice chairman of the board and senior technology officer for Biopure, for his role regarding the misleading statements. Without admitting or denying the allegations, Rausch consented to a judgment enjoining him from violating federal securities laws and ordering him to pay a $40,000 penalty.

Early last week, Biopure also reported a submission to regulatory authorities in the UK seeking approval for the use of Hemopure to treat anemia (MDD, July 12, 2006). The product already has been approved for sale in South Africa.