HOW THINGS HAVE CHANGED SINCE THE 1980S
Given that 2012 represents the 25th anniversary of Biopharm International, it seems appropriate to conclude this article by briefly considering the new biologic drug approval profiles from the 1980s,
and contextualizing them against the more recent approvals considered above.
The first ever biopharmaceutical to gain approval for general medical use was that of Humulin (recombinant human insulin)
in 1982. Throughout that decade, nine such products were approved in the US (see Table II). These products were expressed
mainly in E. coli or mammalian cell lines, with one product being produced in yeast. These expression systems remain dominant to this day.
Table II: Biopharmaceuticals approved by FDA in the US during the 1980s. This era predates the EMA centralized approval system
in the EU, although many of these products were also approved in several individual EU member states during this period. Note:
EPO is erythropoietin, GH is growth hormone, IFN is interferon, rh is recombinant human, and tPA is tissue plasminogen activator.
Products approved in the 1980s were mainly hormones and cytokines, with only one antibody based product among them. The intervening
decades have witnessed a steady increase in biopharmaceutical approval rates, and certainly in their market value.
One of the most striking changes is the current dominance of antibody-based products. During the past 5 years, for example,
one-third of all approvals have been antibody-based, 6 of the top 10 selling biopharmaceuticals globally are antibodies and
antibodies represent by far the single largest category of biopharmaceuticals currently in development. Likewise, target
indication profiles have changed. Today, cancer-targeted therapeutics dominate the market, while only two of the nine approvals
throughout the 1980s targeted this condition.
Another technical trend underlined by comparing products shown in Tables I and II is the evolution of engineered biopharmaceuticals.
The vast majority of products approved throughout the 1980s were un-engineered first generation products, displaying an identical
amino acid sequence to mainly native human regulatory proteins such as insulin and human growth hormone. The 1990s witnessed
the approval of the first wave of engineered products (e.g., fast and slow acting insulin analogues chimaeric and humanized
antibodies as well as PEGylated products). An ever-increasing proportion of product approvals are now engineered to tailor
their therapeutic properties in a predefined way. Fourteen of the 19 products (almost 75%) approved in 2010 and 2011 are engineered.
The biopharmaceutical sector has certainly matured rapidly since the 1980s. Depending on the specific year considered, anywhere
between 20–25% of all genuinely new drug approvals in the EU and US are produced by modern biotechnological means. For example,
Abbott's antibody product Humira (adalimumab), has a projected sales value of $9 billion for 2012 that will almost certainly
displace Pfizers' Lipitor and Sanofi/BMS' Plavix as the world's most lucrative drug this year.
The pace of discovery and innovation in the biotechnology research sphere continues to increase exponentially. The next 25
years will almost certainly witness the discovery, development, and approval of biopharmaceuticals that we cannot even envisage.
In 25 years time, the authors of the 50th Biopharm International special edition will have much to discuss.
GARY WALSH works in the Industrial Biochemistry Program of the Department. of Chemical and Environmental Sciences, Materials and Surface
Science Inst., Univ. of Limerick, Limerick City, Ireland, and is a member of the BioPharm International editorial advisory
1. G. Walsh, Biopharm Intl. 23 (10) 30–41 (2010).
2. G. Walsh, Biopharm Intl. 22 (10), 68–77 (2009)
3. G. Walsh, Biopharm Intl. 21 (10), 52–65 (2008).
4. G. Walsh, Biopharm Intl. 20 (10), 56–67 (2007).
5. R&D Pipeline News, Special Edition (La Merie Business Intelligence, March 2010),
6. T. Ransohoff, "Global Trends in Mammalian Cell Culture Capacity and Biomanufacturing" (2011), presentation available