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Mr Fenton-May is All-Wales quality control pharmacist at St Mary's Pharmaceutical Unit, Cardiff |
The Clinical Trials Directive 2001/20/EC was brought into UK law through
the statutory instrument SI 2004/1031 on 1 May 2004. This brings into
force the controls on the preparation and testing of clinical trial materials,
now known as Investigational Medicinal Products (IMP).
It may surprise many that this is the first time that any legal controls
are imposed on the preparation of trial materials, which are used to
judge whether or not a licence is granted for the marketing of medicinal
products. Such controls are to be welcomed — it is 35 years since
controls were placed on the manufacture of medicines. It is only now
that the fundamentals behind the marketing of licensed medicines are
to be controlled.
All clinical trials products will now have to be made under a Clinical
Trials Authorisation (CTA) in a licensed site, with a manufacturer’s
authorisation for investigational medicinal products (IMP[MA]), issued
by the Medicines and Healthcare products Regulatory Agency (MHRA) and
released by a Qualified Person (QP). The trials will have to be under
the control of a named sponsor whose responsibility it will be to ensure
that all the regulations are complied with. The gains that will be accrued
should easily outweigh the hassle of the inevitable bureaucracy, which
is designed to ensure the quality of IMPs and the protection of patients
on the trial and future users of medicines.
The increasing sophistication of modern medicines requires an approach
to validation of trial data and materials which is suited to the 21st
century rather than the 19th century. It is this data, based on the trial
products, which goes to justify the marketing and use of the medicine.
We are all aware of what happens when the foundations of any structure
are faulty.
Initial concerns regarding the future viability of non-commercial trials,
due to the difficulty surrounding the definition of a potential sponsor
particularly for multi-centre trials, has been overcome by a healthy
dose of good British compromise. Where responsibility can be apportioned
between involved bodies then multiple sponsors can be named. The continuance
of these multi-centre, non-commercial trials is essential to the future
health of the public. It was only through public funding that the health
gains of aspirin in heart disease prevention, magnesium sulphate in pre-eclampsia,
the complex multi-product regimens from different companies used to treat
cancer and HIV, and many other non-profitable, or non-company specific,
medicines are known.
On the introduction of the statutory instrument there is an allowance
for the creation of QPs in the hospital pharmacy via the “Grandparent
Clause”, however, future QPs will be required to qualify via the
permanent provisions. Unless those provisions are changed to allow experience
in the preparation of IMPs to be recognised as a basis for QP qualification,
then the NHS will be unable to release IMPs in the future. This issue
will need to be addressed as a matter of urgency if we are serious about
the continuance of non-commercial trials in the NHS.
As an interim it is incumbent on all who comply with the “Grandparent
Clause” to register as a transitional QP under the existing statutory
instrument. It must be noted that these rights will expire in two years.
Registration now will safeguard the near future and give breathing space
for the arguments to develop on the evolution of future QPs in the health
service. This is a problem unique to the UK. Our European colleagues
are automatically eligible, as pharmacists, to become QPs.
Take the lead
All these trials are concerned with the use of medicines, and pharmacy
must take a lead role in advising on the implementation of the law. There
are strategic alliances to be formed with the research and development
leads and the ethics committees, both of which are given strength in
the new law. But hospital pharmacists, who are charged with the keeping
of all investigational medicinal products in hospitals, and have the
experience of the regulatory authorities through their licences with “specials”,
are in a commanding position to take a lead on advising on the supply
and handling of the trial materials. Guidance on the interpretation of
the statutory instrument and the basis of a good practice guide is available
on the Department of Health sponsored website, www.ncchta.org
There is a degree of foreboding within the multi-professional groups
looking after clinical trials due to the added bureaucracy that is now
being introduced. Many fear that it is the death knell of the local entrepreneurial
researcher and that all but the largest commercial clinical trials will
now cease. This is not the aim of the directive, nor the subsequent statutory
instrument, and it is the responsibility of hospital pharmacists who
have experience in the preparation and handling of “specials”,
and the incumbent bureaucracy, to assure other health care colleagues
that this statutory instrument is to be welcomed and not regretted.
It is to be hoped that the regulations are seen as nothing more than
good practice which is currently being implemented by the majority of
sites, but will now have to be monitored and validated. The good clinical
practice inspections, against the International Conference on Harmonisation
Good Clinical Practice (ICH GCP) guidelines, are new but we are privileged
to be served by a practical, supportive regulatory authority and compliance
will not be an issue to the majority.
In summary we are now entering a new phase in the assurance of the quality
of medicines. The quality of the test substance is to be controlled,
the circumstances in which it is used will be controlled and each trial
will be registered (Pharmaceutical Journal 2003;271:618–22), and
an outcome noted, whether it be good, bad or indifferent. This is not
before time, bearing in mind the current complaints in the press regarding
the lack of reporting of clinical trials information. As quoted in the
BMJ, “there have been some one million clinical trials since 1948
but the results of only half have ever been published”. Even though
the European database is currently only available to regulatory authorities
it will be an improvement on the current situation. We can now be assured
that the information will be made available to those making decisions
on awarding licences for the marketing of medicinal products. |
Hospital Pharmacist