A Biotechnology Industry Organization task force is developing a policy on generic biologics with the goal of presenting it to the BIO board ahead of the association's annual meeting at the end of June.

The BIO task force is led by MedImmune Chairman Wayne Hockmeyer, PhD. The group includes scientific representation from large, medium and small biotech companies, BIO VP & General Counsel Stephan Lawton told a UBS Warburg conference May 22 in New York City.

BIO will "probably have a board vote on it at the San Diego annual meeting" June 25-27, Lawton said.

BIO does not currently have a board-adopted policy on generic biologics. When Sen. Hatch (R-Utah) began discussions about a possible reopening of the Waxman/Hatch Act in 1999, BIO took the position that generic biologics should not even be raised.

Hatch, however, continues to emphasize his view that generic biologics will inevitably be debated as the federal government's role in pharmaceutical purchasing increases under a Medicare prescription drug benefit (¹ [A#00630220023]).

In crafting a position on generic biologics, BIO will need to balance the interests of larger members, who may view the issue primarily as a threat to established products, against smaller start-ups who may see an abbreviated approval process as a shortcut to market.

"I think it is fair to say that it is the position of most, if not all, members of the biotechnology industry that" there is no "such thing as a generic biologic," Lawton said. "There is certainly no such thing as a generic biologic under Sec. 351 of the Public Health Service Act. The ANDA provisions apply only to new drugs."

"In addition, I think it is also fair to say that, as a general rule, the scientists at [FDA's Center for Biologics Evaluation & Research]...are extremely cautious, and shall we say extremely conservative, over the concept of allowing a follow-on version of a multi-source biological product on the market in the absence of clinical trials," Lawton said.

He cited remarks by CBER Director Kathryn Zoon, during a recent Food & Drug Law Institute meeting.

Zoon told the April FDLI session that "I don't believe the agency has changed its position" on the issue since former FDA Commissioner Jane Henney, MD, declared during her confirmation process that "there will not be generic biologics."

"Clearly Congress is evaluating this area and is looking for a variety of advice regarding biological products and their ability to be looked at in the context of this program," Zoon said. "I think the agency will continue to speak to the scientific issues and the health and safety of patients receiving these products."

"There are many, many scientific concerns the agency has identified," Zoon said.

"Because of the nature of biologics, you have concerns about the whole production process," Zoon said. "With small molecules, one can know where every atom is," but "with biological products, you don't really have a homogeneous product. You have a defined range of biological components, in which you find consistency in a particular biological outcome."

"The problems with immunogenicity of biological products, especially for therapeutic biologics, are considerable," she said. Zoon cited as an example a manufacturing change for a human growth hormone product that led to increased immunogenicity until the process was revised.

Zoon's comments were also cited by Genentech Director-Government Affairs Heidi Wagner during a recent Schwab Washington Research Group healthcare conference in Washington, D.C.

"The science of biotechnology is really very different than the science of what we think about in terms of traditional pharmaceutical products," Wagner told the May 9 Schwab WRG session.

"Biotech products are very largely defined by the process which it has taken to actually produce a product," Wagner said. She cited the six-week long production process for the breast cancer therapy Herceptin (trastuzumab).

"It is not just a recipe for what Herceptin is....It is not just a matter of the components that go into Herceptin, it is actually how you cook them," Wagner declared. "The process is very particular, very specific, very unique, and it is our process," Wagner said.

"We are very much in the budding stages of this debate, and great scientific minds really do differ so far on this concept," Wagner said. "Many members of Congress do not even realize that there's a difference between a biotechnology process and regular, traditional pharmaceutical chemical-entity oriented processes."

"It is not an issue of we don't want generic products to come into the biotechnology industry as a way of eating into our profits," Wagner maintained. "It is very much an issue of the science does not exist today."

There are already six competing versions of human growth hormone on the market, Wagner noted. Although "they are not generic versions," the "competition...has actually worked quite well to keep the price of that product very affordable," she maintained.

Even if a pathway were to be established for the approval of generic biotech drugs, "there are economies of scale that you are able to take advantage of in the traditional process that really may not exist when it comes to biotechnology." As a result, "you really may not be able to procure the kind of savings that generics are able to procure on the traditional drug side."

Generic Pharmaceutical Association President William Nixon offered a different point of view during the Schwab WRG conference.

"There is no question that a number of our companies have the ability to move into this area when a regulatory pathway has been approved by Congress," Nixon said. "The technology is out there. Many of the barriers that once inhibited generic biologics have been removed over the last several years."

"It is very easy in any debate to say that the science is so complex that we can't understand it," Nixon observed. However, he maintained, "the interchangeability is already taking place within the biotech industry. They are sharing data and information. They are transporting it....The biologic industry has already shown that you can. They've moved their plants, they've changed their processes."

The ability of biotech companies to transfer production to a new plant or to a licensing partner should not be considered evidence that it is possible for outside manufacturers to produce comparable agents, Wagner responded.

"The baseline of that process is ours....It is based on original thinking and original knowledge," Wagner said. "We even have to have FDA come in and approve process changes if we want to make them, and at times we are even required to get new clinical testing done. It is very, very different from a generic company that is not privy to our process claiming to have the same end result."

"I'm not saying that at the end of the day, you couldn't have a very similar product," Wagner said. "But that is a different product. That is not a generic."

"There are already generic biologics out there," Nixon countered, citing the FDA approval of a generic version of Serono's fertility drug Pergonal (menotropins) in 1997.

Nixon noted that, before 1997, there were competing fertility hormones on the market "all within a dollar or two in price. It wasn't until the equivalent version came on the market that it dropped down $10 or $15 less than what people were paying for the brand."

Wagner suggested that there may be a basis for different regulatory structures for different types of biological products.

"I think that there is a difference between those kinds of products that are biologics but that do not involve a biotechnology...process, where the process is very important," Wagner said.

During the UBS Warburg meeting, Lawton noted that the Center for Drug Evaluation & Research, which has responsibility for hormone products like insulin and human growth hormone, is moving towards an abbreviated approval pathway for those products.

One model that CDER may be considering would be to use the approach by which Duramed's conjugated estrogens "A" product Cenestin was approved: "they would rely on what they call their 'finding' of safety and effectiveness for previously approved products, but require at least confirmatory safety studies by clinical trials," Lawton said.

The approach "has been rumored" but "does not yet represent clearly policy of FDA, but it is an issue that is being reviewed," Lawton said.

BIO Generic Biologics Task Force Hopes To Complete Proposal In June

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