Therapeutic hormones - Pharmaceutical Biotechnology: Concepts and Aapplications - page 324

Box 11.6

Product case study: Ovitrelle

Ovitrelle (tradename in EU, sold as Ovidrel in the USA and also known as choriogonadotropin
alfa) is a recombinant hCG approved for general medical use in the EU and USA in 2001. It is
indicated for the treatment of female infertility due to anovulation and for patients undergoing
assisted reproductive technology. It is used to trigger fi nal follicle maturation and luteinization
after follicle stimulation.
The glycoprotein hormone, consisting of an -subunit, displays an identical amino

acid sequence and very similar glycosylation detail when compared with native hCG. It is pro-
duced in an engineered CHO cell line and, after cell culture, the product is purifi ed from the
media by multistep chromatography, ultrafi ltration and nanofi ltration. The fi nal product also
contains mannitol, methionine, poloxamer188 sodium hydroxide and ortho-phosphoric acid
and is presented in either vials or pre-fi lled syringes. The product is administered subcutane-
ously. Following s.c. administration, maximum serum concentration is usually witnessed after
12-24 h and the product is eliminated with a mean terminal half-life of approximately 29 h.
Absolute bioavailability is of the order of 40 per cent.
Pivotal pre-approval safety and effi cacy was assessed in a randomized, open label, multicen-
tre study of infertile females undergoing in vitro fertilization and embryo transfer. The primary
effi cacy parameter was the mean number of oocytes retrieved, which (at 13.6) was similar to
the number retrieved when urinary-derived hCG was used. Serious potential side effects can
include ovarian over/hyper-stimulation, sometimes with pulmonary or vascular complications.
The product is marketed by Serono Inc.

α - and a β

recovered from the animal (either surgically or, more usually, non-surgically), and are often main-
tained in cell culture for a short period of time. A single embryo is then usually reimplanted into
the donor female, while the remaining embryos are implanted into other recipient animals, who
act as surrogate mothers, carrying the offspring to term.
This technology is most often applied to valuable animals (e.g. prize winning horses, or high
milk-yield dairy cattle) in order to boost their effective reproductive capacity several-fold. All the
offspring will inherit its genetic complement from the biological mother (and father), irrespective
of what recipient animal carries it to term.
Gonadotrophins usually utilized to induce a superovulatory response include porcine FSH (p-FSH),
porcine LH (p-LH) and PMSG. p-FSH is extracted from the pituitary glands of slaughterhouse pigs.
The crude pituitary extract is usually subject to a precipitation step, using either ethanol or salts. The
FSH-containing precipitate is normally subjected to at least one subsequent chromatographic step.
The fi nal product often contains some LH and low levels of additional pituitary-derived proteins.
p-LH is obtained, again, by its partial purifi cation from the pituitary glands of slaughterhouse
pigs. Although the target recipients are almost always cattle or horses, in both cases a porcine
source is utilized. The use of a product derived from a species other than the intended recipient
species is encouraged as it helps minimize the danger of accidental transmission of disease via
infected source material (many pathogens are species specifi c).