Linda Anderson: MHRA welcomes new directive on herbal products |
Most herbal products in the UK are unlicensed. One problem with
this is that there is little or no information for patients regarding
indications
for use, use in pregnancy and lactation, and potential interactions
with conventional drugs, said Linda Anderson, of the Medicines and
Healthcare products Regulatory Agency. The greatest problem is that
the MHRA has no knowledge of the products or their ingredients and
there is no requirement for these products to meet any safety or quality
standard.
The European Commission started work on new legislation in 2002 to regulate
herbal products and the Directive on Traditional Herbal Medicinal Products
2004/24/EC was adopted on 31 March this year. Member states must have a
registration scheme in place by October 2005, and all products legally
on the market now can remain so for seven years. Dr Anderson explained
that the new legislation will simplify the system and remove regulatory
hurdles. It is only for minor conditions where no medical intervention
is needed and will only apply to oral, external and inhalation products.
The product must have been available for 30 years in the EU, or 15 years
in the EU and 15 years in other specified territories.
Dr Anderson highlighted the advantages of the system: it will ensure the
quality of herbal products via the same rigorous process undertaken for
licensed medicines; the composition will have to be declared; all contraindications
and guidance for use will be identified and products will have a patient
information leaflet and a label; and a warning that if symptoms persist
patients should consult their doctor will be a legal requirement. Pharmacovigilance
and adverse drug reaction reporting will be the same as for authorised
products.
In contrast, the disadvantages of the system are that products have to
demonstrate “no evidence of risk”, which is not the same as “evidence
of no risk”, said Dr Anderson. In addition, the onus is on the competent
authority to identify the risks and request further data. There is no requirement
for clinical trial evidence — the directive is based on long-standing
use of the product — so the question of efficacy will remain.
However, Dr Anderson said that the MHRA welcomes the directive. She said
that it puts in place public health safeguards and ensures consumer choice. “The
pros outweigh the cons,” she added. “It offers considerable
advantages to patients and there is a major benefit for pharmacists in
advising patients on choices.”
A participant at the conference said that control should be with pharmacists
rather than untrained staff in health food shops. Dr Anderson replied: “Most
products that register under the scheme will be seeking general sale list
status ... it is difficult legally to prevent this while a GSL category
exists.” That is why patient information is so important, she added.
Natural products key to drug discovery
Plant-derived drugs have been the source of a large number of extremely
important compounds, said David Newman of the National Cancer Institute,
Bethesda, Maryland.
The intellectual underpinnings of over 70 per cent of drugs discovered
between 1981 and 2002 came from the natural world.
Only 28 per cent of all approved anti-tumour agents are synthetic, said
Dr Newman. Plant-derived drugs currently in use in the treatment of cancer
include taxol, podophyllotoxin, the vinca
alkaloids and camptothecin.
Despite what pharmaceutical companies might say, statins started from a
fungal product. “These are the highest selling products in the world
... they are made in a laboratory but the intellectual input came from
mother nature,” said Dr Newman.
Peter Houghton, King’s College London, and chairman of the session,
asked why funding for natural product research is lacking.
Dr Newman replied that there was a perception that it was a long-term process. “Up
until 2000, that was a true statement. However, with the advent of hyphenated
techniques it is now feasible to go from a microbial or plant extract to
a structure in less than three weeks.” But a huge budget would be
needed, he added.
Trial design for herbal products
When extrapolating data from clinical trials, it is dangerous to talk
about the efficacy of herbs in terms of generic monographs, said Peter
de Smet,
from the Scientific Institute of Dutch Pharmacists, the Netherlands. “We
can only talk about the efficacy of specific herbal products and then
only if the batch to batch variation is within acceptable limits.”
Clinical trials usually concentrate on determining whether the product
works, ie, is it better than placebo? “In my view it is more important
to find out how well it works relatively,” said Dr de Smet. To do
this, the minimum important difference needs to be defined and then the
number needed to treat can be calculated.
In the 1990s there was a trend of conducting trials that compared herbal
products with synthetic drugs. “This is not always enough,” said
Dr de Smet. He explained that if the endpoint of the study is a rating
scale then it is important to have a three-arm trial of herbal versus synthetic
drug versus placebo, in order to determine whether the assay being used
is sensitive in the study population.
It is also important to determine the add on value of herbal products by
comparing synthetic drug plus herbal versus synthetic drug plus placebo. “We
know that in many cases herbal products are used in addition to conventional
products,” said Dr de Smet. Moving on to safety issues Dr de Smet
said that there can be indirect health risks involved with the use of herbal
products due to their modest effect size. For example, using a herbal product
may replace or retard the start of a well proven conventional treatment.
Another problem highlighted by Dr de Smet was the inadequate control of
access to herbal products. Products that have been banned are still available
on the internet, said Dr de Smet.
The addition of undeclared substances to herbal products is a further problem.
In the past well known pharmaceuticals have been added to herbal products. “But
now we see a new trend of derivatives being added to the herb,” explained
Dr de Smet. For example, a sildenafil-like compound has been found in Hua
Fo. This raises additional safety issues.
In summary ...
Peter Houghton concluded the session by emphasising
that there is no difference between natural products and synthetics — they both
have the benefits and problems that all medicines have. “As
pharmacists, we have to be scientific about this and educate
and inform our fellow health professionals and the public that
these
things are medicines, they have risks and benefits, so they can
make an informed decision.” |
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