Biogenerics

Will they ever materialize and what will their potential impact be on outsourcing?

Biogenerics actually do exist in some regions (China, India, Eastern Europe), but their widespread introduction into major pharmaceutical markets remains some way off. In January 2006, the European Medicines Agency (EMEA) adopted a positive opinion for Sandoz’s generic growth hormone product Omnitrope. The Sandoz product was described as having demonstrated comparable quality, safety and efficacy to Genotropin, a reference medicinal product already authorized for use in the EU.

There is no doubt that the EMEA’s decision concerning Omnitrope was a major step forward for biogenerics, but this development didn’t herald an immediate breakthrough for biogenerics, as the regulatory process is still being developed to cope with future applications. The FDA also followed a similar line in approving Omnitrope, but it has indicated that it will evaluate follow-on biopharmaceuticals on a case-by-case basis.

It’s the regulators that are going to decide this one, so it will be interesting to see how they react to the pressure exerted on them from all sides. Nevertheless I imagine we’ll be seeing major movement in this area in the next five years. Biogenerics can’t be blocked forever now that the consumer groups have heard about them and expect lower prices. The interest in the cost angle was illustrated in the ongoing biotech patent between Amgen and Transkaryotic Therapies over Amgen’s anemia drug Epogen (Epoetin alfa). In January 2003, the US Court of Appeals for the Federal Circuit upheld a previous ruling that Transkaryotic’s rival drug Dynepo infringed two Amgen patents. Interestingly, the Consumer Federation of America and the National Organization for Rare Disorders backed Transkaryotic in its appeal against the ruling, as they believed that the public will benefit price-wise from the availability of a rival product to Epogen.


Biogenerics — also often referred to as biosimilars — are already a reality outside both the EU and the U.S. Scores of me-too versions of biopharmaceuticals — such as erythropoietin, interferons, Hep B vaccines — are on the market in China, India and South America. Companies like Pliva, now part of Barr Laboratories, have registered their own preparations of erythropoietin in the countries that were part of the former Yugoslavia. In fact the main barrier preventing the advent of biogenerics/biosimilars in the EU and the U.S. is represented by an unclear regulatory and legal framework. However, recent developments on both sides of the Atlantic suggest that the situation is evolving, biogenerics being likely to become a reality in a three- to five-year horizon! At least initially the impact of the advent of biogenerics in the EU and the U.S. is unlikely to have a major impact on the outsourcing space, as a substantial share of the likely developers and marketers of this type of products are firms such as Barr-Pliva, Sandoz, Teva-Sicor, which are extensively backward integrated.


I definitely see biosimilars materializing in both the U.S. and European markets. Recent developments in Congress have gained momentum, which will lead the way towards the development of regulatory requirements for biosimilar approvals. Since the cost of goods will not be significantly less than the innovator products, the impact on outsourcing will be minimal, as the market will be served by a small number of companies that can afford to develop the infrastructure or outsourcing relationships to launch their biosimilar products. Many of these companies have already made such investments or have existing fill/finish facilities to satisfy their manufacturing needs.


Biogenerics will exist. The government wants them. Henry Waxman and Charles Schumer are sponsoring, in the House and Senate, respectively, the Access to Life-Saving Medicine Act. In the small molecule field, the generic version is chemically identical to the brand name. In biogenerics this is not required; the bills talk about “comparable” and “interchangeable” versions. They need to be “essentially identical” and “highly similar.” The biotech products are so complex, some containing many amino acid units, that very similar chemicals may have the same effect and be interchangeable.

Outsourcing opportunities may develop along with new alliances. The manufacturer of a biogeneric would certainly be in a stronger position vis-a-vis the generic company than in the small molecule field, where a generic firm may have a choice of several manufacturers for a specific drug. Issues of exclusivity would come into play: would the generic company agree to let the manufacturer sell to competitors?

Of course, there is an argument against allowing biogenerics, because the generic companies do not have to go through the same studies to prove safety as the discoverer. Some argue that this creates an unlevel playing field.


Biogenerics seem to always be just on the horizon, and my prediction that there should be rules shortly has yet to come true. There is certainly more pressure to move in that direction given the current Congress, but no indication that a set of meaningful guidelines will appear any time soon.

If biogenerics were to be approved, it might have a significant impact on outsourcing. The outsourcing capacity for biologics manufacturing has never been large. The possibility of using contract manufacturers to help with the manufacturing would likely rapidly put substantial stress on the system. It would certainly give the biologics outsourcing field a new look.


The evolution of biogeneric drugs is bringing with it considerable controversy, but it appears that the pathway to numerous future approvals is being constructed. With the U.S. Congress moving towards introduction of enabling legislation that is designed to impact prescription drug laws for biogeneric inclusion, and other legislation moving forward to grant substantial periods of exclusivity, FDA-defined product class guidelines will likely take shape. The appearance of “biogenerics” in greater numbers will be inevitable if the products meet “bioequivalence” concerns with defined safety and efficacy. Whether this introduction of a new approval process is a speedy process remains to be seen. Uniformity of definition is still a problem in some sectors but products that technically fit under the “biogeneric” rubric are already on the world market.

How the definition of “biogeneric” is ultimately arrived at will require great care — since the terms in use now don’t necessarily make it clear if we are concentrating on chemically exacting structures, production processes, and/or the product sources. Add to that the questions of therapeutic equivalence and each product will come under considerable scrutiny.

As products become more numerous, and exclusivity issues are addressed, the possibility of contract driven outsourcing for bulk drug, “equivalent” formulations, and identification of “impurities” can be expected to eventually work their way into the testing/production/distribution equations of the future.