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Over the coming years, an increasing number of follow-on biotechnology
products will come onto the market as the patents on originator products
expire. Unlike generic versions of small-molecule drugs, these biosimilar
medicines will not be identical to the originator products and may have
different clinical effects.
In recognition of the fact that biosimilars are not identical to originator
products, the mechanism for gaining European approval for a biosimilar
differs from that for a generic medicine. In particular, it requires
significant clinical evaluation in order to demonstrate that a biosimilar
medicine has comparable safety and efficacy to those of the innovator
product.
The term “biosimilar medicine” comes from EU legislation
governing the approval process, but these products are also known as “similar
biological medicinal products”, “follow-on biologics” and “biogenerics”.
To date, the only biosimilars approved for use the EU have been preparations
of the recombination growth hormone somatropin and of epoetin alfa, but
several more biosimilars are currently being assessed.
The European Generic Medicines Association believes that biosimilar medicines
could improve access and reduce cost pressures on health systems. “Biosimilar
medicines now offer a major opportunity to provide greater access to
affordable healthcare for several life-saving medicines, at least equally
significant to the emergence of generic medicines over the past two decades,” it
says.
The European Medicines Agency (EMEA) has recommended that “the
decision to treat a patient with a reference or a biosimilar medicine
should be taken following he opinion of a qualified healthcare professional”.
Jayne Lawrence, the Royal Pharmaceutical Society’s chief scientific
adviser, stresses that biosimilars cannot be considered in the same way
as small-molecule generics, “They are not generics and must be
treated differently,” she says. “At this stage in the development
of some types of biologics I believe more information is needed to safely
make the decision to substitute a biosimilar product.”
A number of countries, including France, Spain, the Netherlands and Norway,
have already introduced measures to prevent substitution of biopharmaceutical
products. And last week a group of MPs, led by Brian Iddon (Lab, Bolton
South East) urged the UK Government to do the same (see Panel below).
Parliamentary review
A group of five MPs, led by Brian Iddon, conducted
a review of the issues surrounding the introduction of biosimilars
into clinical
practice, hearing oral evidence from seven witnesses. The review
was funded by biotechnology company Amgen. In the report that
followed the review (PJ, 5/12
January 2008, p6), the
MPs recommended that a number of safety measures be introduced “to
ensure that prescribing and pharmacovigilance procedures are
sufficient
to safeguard best practice and offer patient protection”.
The British Generic Manufacturers Association argues that the
evidence taken by the MPs was biased. “Though [the report] is designed
to look like an official parliamentary committee document, it is
not,” the association says. “The BGMA was not asked to
contribute to the report. Neither to our knowledge was any representative
of the biosimilars industry. The ‘evidence’ taken was
thus not balanced.” Nevertheless, a number of the MPs’ recommendations
already apply to biosimilars, the association says.
However, the Medicines and Healthcare products Regulatory
Agency has said it is considering the recommendations in the report and
that the Government will be responding to it.
Further information about the report is available from the office
of Brian Iddon, House of Commons, London SW1A 0AA or by telephoning
020 7219 2096. |
The MPs argued that biotechnology products should always be prescribed
by brand, rather than by their generic name, that patients should be
maintained on the specific medicines on which they started treatment
and that substitution of one product for another should be banned.
The Government has previously said, in response to Parliamentary questions
from Mr Iddon, that when biologics are prescribed they should be “clearly
identified and prescribed by brand name to ensure that patients receive
the exact product prescribed and that their use can be properly monitored”.
The Government has also said that the Medicines and Healthcare products
Regulatory Agency encourages manufacturers to give biosimilar products
a brand name “so that there is no possibility that the pharmacist
can substitute another biosimilar
product when dispensing the doctor’s prescription”.
Complexity
Biologics are large molecules and so complex to produce, Professor
Lawrence explains. Biologics include agents used in a wide range of therapies,
such as vaccines, blood and blood components, allergenics, somatic
cells, gene therapy, tissues and recombinant therapeutic proteins.
They can be composed of sugars, proteins or nucleic acids, or complex
combinations thereof, or in some cases may even be cells and tissues.
And their production may involve isolating molecules from biological
sources or growth in cells. The complexity of biologics means that biosimilar
products will almost certainly use different starting materials or different
manufacturing processes to those used for the originator biologic.
The characterisation of biologics is also extremely complex, Professor
Lawrence adds. A whole range of sophisticated techniques, both physico-chemical
and biological, are required to gain a picture of a biologic. In fact,
different tests may be needed for different biologics.
“The complexity of characterising biologics means it is not possible to
prove that the biosimilar is identical to the reference product,” she
says. “Therefore biosimilars can only be considered as similar
to the reference product — hence the name.
Clinical differences
“It is also possible for biosimilars to exhibit different clinical
characteristics that cannot be detected by standard physico-chemical
and biological testing
and which might lead to rare adverse events, especially immune-mediated
events. All these factors mean that more information is needed about
a biosimilar to make a substitution than is needed to substitute
a small-molecule drug”
However, Professor Lawrence points out that some biologics have been
safely substituted for years, including human growth factor and insulin.
In fact, the panel of MPs suggests that the safety of biosimilars could
be assured once sufficient clinical data exist, suggesting their recommendations
are limited to new biologics coming onto the market.
“If there is a ban on substituting biologics, I would hope that after
sufficient wide spread use of biosimilars the situation would be reviewed
to see if it were possible to substitute biosimilars,” Professor
Lawrence says. “A suitably qualified review panel would be needed
to consider the therapeutic evidence on biosimilars to remove the ban
to substitute,” she adds. |
The
Pharmaceutical Journal