Biopharmaceuticals are drugs derived from living organisms. They are usually complex molecules and are therefore more difficult to consistently manufacture, quantify and purify. Biopharmaceuticals can be classified based on technologies used to produce them as given below:
- Bioengineered vaccine, introduction of recombinant material from a pathogen (virus or bacteria) to induce or increase immune system response (recombinant hepatitis B vaccine)
- Recombinant drugs, recombined fragments of DNA from two or more molecules, to augment, replace or inhibit function of natural proteins (Epoetin alfa)
- Monoclonal antibodies, produced by immune system & bind with specificity and affinity to antigens and removed from the immune system, (Rituxan, Remicade etc.)
- Cell therapy, the use of cell to regenerate or replace dead/damaged cells and tissues (transderm and autoderm tissue engineered skin)
- Gene therapy, the treatment by replacing, manipulating or supplementing malfunctioning genes delivered using a weakened virus (none in the market, but Allovectin 7 & P53 gene therapy in clinical trials)
- Transgenic products, these produced from transgenic organisms (none in the market but Lactoferrin in phase II for GI track infection)
A number of first-generation biopharmaceuticals, which has come off patent or lose marketing exclusivity (first in Europe, then the USA), including alpha-interferon, erythropoietin, human growth hormone, human insulin etc. have opened the door for the manufacture of generic biopharmaceuticals otherwise called biogenerics.
According to some industry estimates, sales of five major therapeutic proteins exceeded US $ 22 billion 2002 and is expected to grow up to $ 42 billion by 2007. With as many as 125 new products reaching market in the next five to seven years and with more than 370 biotech therapeutics in clinical trials, the field of biopharmaceuticals is becoming very crucial. Biogenerics of course will be a follow up activity. Amongst these, first three categories are co-developed by the biogeneric companies worldwide including Indian companies such as Human insulin, Filgrastim, Interferon beta 1a, Interferon alfa 2B, Imiglucerase, Alteplase, Somatropin, Palivizumab, Etanercapt etc.
The most critical issue for the pharmaceutical generic market is the lack of a clear regulatory framework, which makes it very difficult to estimate generic market.
The regulatory need to demonstrate "essential similarity" for biogenerics to a reference product is huge hurdle for the developers unlike small molecule generics.
The complex patent environment surrounding biologics represents a big barrier to the development of biogenerics. The unique aspect of biotechnology patent law and its complex cities certainly represent a futile ground for biopharmaceutical innovators to hinder the development of biogenerics, providing problems to biogeneric producers. In April 2004, the US FDA announced that its policy and legislative guidelines, which will layout the basic scientific framework for biogenerics will be available by the beginning of 2005, which would apply to majority to majority of the biologics marketed under BLAs (Biologics License Applications).
The most important obstacle perhaps is the availability of bulk active biopharmaceuticals through non-patent infringing routes. Many reliable sources are emerging worldwide as contract manufacturing companies such as Boehringer-Ingelheim, DSM biologics, Lonza etc but their focus has been mainly on exclusive custom manufacturing of new biologicals under development by biotech or biopharmaceutical companies. Given the current capacity shortage particularly for mammalian cell culture, the strategy that these contract manufacturing companies remain committed towards the innovator biopharmaceutical companies then hurdle for biogeneric companies will not get reduced at least in the near future.
In addition, the advancement of analytical methods will also play a major role as technologies in this field may allow a more accurate characterization of macromolecules, opening new frontiers in terms of demonstration of equivalence or even essential similarity.
There is no reason to think that biopharmaceuticals will enjoy indefinite monopolies just because they are difficult to make and regulatory processes are lacking. As health costs continue to rise, biogenerics could offer an attractive source of savings for governments and consumers alike. Companies already working on generic biopharmaceuticals include Cangene (Canada), GeneMedix (UK), IVAX (USA), Microbix (Canada), Rhein Biotech (Germany) and Teva (Israel). Several Indian companies are also gearing up to take up this newly emerging challenge. Though success in chemical based generics for Indian companies are well known yet the fate of biogenerics by Indian players will be interesting to watch in the near future.
- (The author is chief scientific officer, Shasun Chemicals and Drugs Limited, Chennai)