CLINICAL TRIALS
T
he year 2008 marked a signifi cant granted to products developed specifi cally for paediatric research networks. In 2009 the
step forward for the development of children. agency expects to have the resources available
medicines for children when new EU The regulation appears to be having the to identify these networks, and will set up a co-
legislation bore its fi rst fruit in the form of a desired effect: by September 2008, the EMEA ordination group to take the initiative forward.
paediatric drug for serious fungal infections. had received more than 290 applications To help achieve another of the regulation’s
In September, the European Medicines for PIPs or waivers. 64% of these were for
aims – increasing the amount and quality of
Agency (EMEA) recommended the approval of
products that had yet to be authorised for paediatric information available on drugs – the
Merck Sharp & Dohme’s Cancidas (caspofungin
marketing, while 34% were for approved commission is planning to make paediatric trial
acetate) for use in children, on the basis of
products, still under patent, for which data publicly available on the internet.
clinical trials conducted in accordance with a
companies were seeking a new indication, Two types of data will be involved: pre-
paediatric investigation plan (PIP). The agency’s
pharmaceutical form or route of administration. trial protocol information, such as the trial
scientifi c committee, the CHMP, concluded
However, a mere 2% of applications, six in design and exclusion/inclusion criteria; and
that the data on quality, safety and effi cacy
total, related to PUMAs. This suggests that one results-related information, including details of
supported this extension of indication.
of the aims of the regulation – to encourage outcome measures, randomisation, adverse
The move was a small, but important,
the development of paediatric forms of older events and data interpretation.
fi rst step in the process of building up an
products – is not being achieved. The data will be drawn from the existing
armamentarium of therapies developed
Nonetheless, the EMEA’s go-ahead for EudraCT database – a public website will be
specifi cally for use in children. Over the coming
paediatric Cancidas in September marked established containing a subset of information
years many hundreds more medicines will
a real step forward. The product is already regularly updated from EudraCT.
gradually gain paediatric indications in Europe,
available for paediatric use in the US, where it
appropriate forms
refl ecting the fact that in terms of drug dosing
Another initiative launched during 2008 was
and formulation, children are not just small
In terms of drug dosing and
a draft EMEA guideline to help companies
adults.
Many medicines currently used to treat
formulation, children are not just
develop the most appropriate forms of
medicines for specifi c age groups. Some
children in European countries have not small adults
guidance is already available, covering
been studied or authorised for such use, and
physiological and pharmaceutical issues as well
market forces alone have not been enough
as the use of excipients with known effects in
to encourage pharmaceutical companies
was approved by the FDA in August for use in
humans. But the EMEA says the documents
to develop and test paediatric medicines.
children aged three months and older.
have limitations and that additional guidance is
According to the European Commission, this
The PIP for Cancidas was fi rst OKd by the
needed.
has caused a number of problems such as
EMEA in February 2008, on a recommendation
inadequate dosing information, leading to a
from the agency’s paediatric committee,
Different subsets of the paediatric population
higher risk of ineffective treatment, side-effects
and then amended slightly in May. The
– pre-term newborns, infants and adolescents
and sometimes death.
product will become available in Europe
for example – often need different forms of
The US has had legislation in place
once the commission has issued a marketing
drugs. The new guidance is expected to help all
for several years, in the form of the
authorisation (this has to be granted within two
concerned, from industry through regulators
Pediatric Research Equity Act and the Best
months of the go-ahead from the EMEA).
to patients, by introducing harmonised
recommendations on aspects of paediatric drug
Pharmaceuticals for Children Act, both of
positive mindset
development. Importantly, children themselves
which were recently re-authorised by the FDA
The EMEA itself is pleased with progress on
will see benefi ts in terms of convenience,
Amendments Act (FDAAA). But Europe has
the paediatric front so far. Its executive director,
improved safety and better compliance with
lagged well behind in this area.
Thomas Lönngren, told Scrip that the PIPs
therapy.
To fi ll the gap, the commission drafted the
submitted so far had been very satisfactory,
Unfortunately, it will be some time before
paediatric regulation, which was approved in
and that companies had a “positive mindset”
the guidance is ready, as the draft version is not
2006 and came into effect in January 2007. It
towards the requirements.
expected to be ready for public consultation
offers a mixture of incentives for conducting
Moreover, he said the agency was learning
until the fi rst half of 2009. Moreover, because
paediatric trials, together with mandatory
“step by step”, reviewing the way it operates
views in Europe on paediatric formulation
requirements.
and improving its procedures. It has updated
appear to differ widely, these will have to be
The incentives include a six-month extension
its procedural advice to companies, and issued
taken into account, so the fi nal version will
to supplementary protection certifi cates
new guidance on compliance with PIPs and a
probably not be ready until the end of 2009,
(which lengthen effective patent protection).
new version of the application form.
the EMEA estimates.
As for the requirements, companies intending
But the new responsibilities have put a
In the meantime, companies should be aware
to apply for approval of a new drug have to
strain on the EMEA’s resources. The agency
of the next major milestone in implementing
produce a PIP, which outlines the trials they
is receiving some 20-30 applications for PIPs
the EU paediatric legislation. Since July 2008,
plan to conduct in children, or otherwise seek a
and waivers each month, and in all probability
the PIP/waiver requirement has applied only
waiver or a deferral. The PIP must be agreed by
each of these will cover more than one
to new substances not yet approved in the EU.
the EMEA’s paediatric committee. The results of
indication, requiring individual review. “We also
But from January 2009, it will also apply to new
the trials must be included with the marketing
have regular meetings with industry, so it is a
indications, pharmaceutical forms and routes of
authorisation application.
lot of work,” Mr Lönngren said. The EMEA is
administration of existing drugs.
Waivers can be granted if the company
accordingly taking on more staff, and has got
shows that the product is not appropriate for
approval to recruit in both 2008 and 2009.
Ian Schofi eld is a principal
use in children (such as drugs for Alzheimer’s
analyst for Informa Pharma.
disease and certain cancers), or that giving it to better implementation
children would be unsafe.
Plans are also afoot to improve the
For older, off-patent drugs, a PUMA – or
implementation of the regulation, including
paediatric-use marketing authorisation – can be
the construction of a European system of
78
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