using biotechnology products will not be covered,
although they could be classed as biological pro-
ducts. Similarly, pluripotent stem cells are cur-
rently investigated for the manufacture of tissues
for grafting, but these are not biotechnology
therapeutics themselves.
There are approximately 1250 biotechnology
companies in the United States and Canada,
about half that number in Europe and smaller but
growing numbers throughout the rest of the world
(especially Israel, Korea and Australasia). These
companies are usually much smaller than the large,
fully integrated ‘pharmaceutical’ companies
(‘large pharma’) on the East coast of the United
States or in Switzerland. Small companies’
research activities may be restricted to the precli-
nical discovery and early-stage clinical investiga-
tion of compounds; therefore, their business
environment and practices differ from large
pharma. On the other hand, all of the less numerous
but much bigger pharmaceutical companies are
engaged in biotechnology, one way or another.
Somewhat arbitrarily, we shall use the term
‘Biotechnology Company’ rather loosely in this
chapter to mean this type of small organization.
One wag in the investment community has given a
further definition: a biotechnology company is a
pharmaceutical company without revenues! The
term ‘Biotechnology Products’ refers to the com-
pounds themselves, regardless of the size of the
organization developing them.
Before we turn to the products themselves,
however, we would like to draw attention to
when biotechnology brings special ethical aspects
to the clinical trial. As we shall see below, some of
these therapies require extraordinary procedures,
such as the deliberate immunization of normal
volunteers to foreign blood groups, or the intro-
duction of exogenous genes into patients. Ensur-
ing that consent is truly informed issine qua non,
even though, sadly, this was not the case in a
recent disaster when a patient in an early-phase
gene therapy study died. We return to ethical
issues at the end of the chapter because they
must be considered in relation to the technical
aspects of investigational biological products;
nonetheless, these should be foremost and not
afterthought.
22.3 Regulatory considerations
In most countries regulation of drug and biological
compound development and marketing has usually
derived from governmental response to crisis.US perspective
The initial legislation affecting biologics was
the Safe Vaccines and Sera Act of 1904, the
focus of which was the development of safe, pure
and potent vaccination preparations. At that time
this was the responsibility of the Department of
Agriculture. This was somewhat superceded by the
Public Health Service Act (1944), written princi-
pally with blood products and prevention of the
transmission of disease by infusion in mind.
It was not until 1972 that biological products
were brought under the same regulatory frame-
work as chemically synthesized, small molecule
drugs. TheFood andDrugAdministration(FDA), a
single branch of the Public Health Service, then
accepted the responsibility for biologics, upon
their transfer from the Department of Agriculture;
within the FDA, a designated Center for Biologi-
cals Evaluation and Research (CBER) was created.
This unified approach progressed further in 2005,
when most (but not all) biological products were
transferred within FDA from CBER to the Center
for Drug Evaluation and Research (CDER), the
latter comprising the ordinary reviewing divisions
with which readers will be familiar. Similar
historical events stimulated other models in other
countries.
In the United States and elsewhere, evidence of
this convergence of biological and nonbiological
products is evidenced by:IND regulations (there are no unique regulations
for biologics undergoing experimental study)Similar good clinical practices guidelinesVarious International Conference on Harmoni-
zation initiativesGood manufacturing practices280 CH22 BIOTECHNOLOGY PRODUCTS AND DEVELOPMENT