UK Drugs
The Medicines Healthcare Products Regulatory Agency (MHRA) safeguards public health by ensuring that all medicines on the UK market meet appropriate standards of
safety quality efficacy
Safety aspects cover harmful effects; quality relates to development and manufacture; and efficacy measures of the beneficial effect of the medicine on patients.
The Agency achieves its objective through:
- a system of licensing before the marketing of
medicines;
- monitoring of medicines and acting on safety concerns after they have been placed on the market;
Licensing of medicines
Medicines, which meet the standards of safety, quality and efficacy, are granted a marketing authorisation (previously a product licence), which is necessary before they can be prescribed or sold. The MCA examines all the research and test results in detail, before a decision is made on whether the product should be granted a marketing authorisation.
Is it a medicine?
A medical product is either a medical device (CE marked) or a medicine ( has a PL ). A medicine is defined as (Directive 65/65 EEC)
"Any substance or combination of substances for diagnosing, treating or preventing disease that changes physiological functions."
Medicines can be solids such as lozenges, pastilles, tablets and capsules or lotions, creams, ointments, skin patches, aerosols, eye drops, suppositories and injections.
Appliances, instruments and materials, for example, punctal plugs and contact lenses, are devices not medicines and require CE certification from the Medical Devices Agency (MDA)
Contact lens lubrication fluids are however medical devices (CE marked) since they are accessories. Corneal lubrication fluids are medicines.
The main consideration between a product being a device or a medicine is in its indications for use. CE marked products are governed by the MDA (Medical Devices Agency). Products that require a product licence ( drug registration ) are governed by the MCA (Medicine Control Agency). There are occasions when the two bodies confer in borderline cases where a CE marked device has medicinal applications over and above its intended use. (for example Hylo-Prompt with specific dry eye lubrication for Sjogrens syndrome). The Drug Tariff has been set up for such CE marked devices to enable access to patients via prescription and reimbursement for the supplier. Products migrated to the Drug Tariff are listed in Mimms and BNF which are specifically for POM/P reference.
Most medicines are clearly identifiable as such and are subject to EC marketing authorisation procedures. However, some products, for example, food supplements, are not so easy to distinguish a medicine from. These are known as "borderline products".
Dietary supplements, containing such familiar substances as vitamins, amino acids or minerals, are generally subject to food safety and food labelling legislation rather than medicines control. This is the case for Pure Focus Spray.
However, if the product contains a pharmacologically active substance or make medicinal claims; then it would fall within the definition of a medicinal product and be subject to medicines control.
Exemptions from licensing
Medicines whose active ingredients are entirely herbal ( consisting of plant extracts only with water or other inert substances) are EXEMPT from licensing.
Herbal remedies can be only be supplied to a patient
after a consultation
made on
the premises
no written recommendation as to its use
no commercial name is given
to it
Herbal medicines combined with vitamins or minerals are NOT exempt and require a marketing authorisation just like other licensed medicines. A list of herbal ingredients which are prohibited or restricted in medicines exists on the MCA website.
When seeking a licence for herbal medicines, many companies have difficulty proving product efficacy. This arrangement protects the public but tends to restrict choice.
Special needs
Some patients may have special clinical needs that cannot be met by licensed products. For these individuals the law allows the supply of
"Specials" and imported unlicensed medicines
These cannot be supplied if an equivalent licensed product is available which meets the individual patient's needs.
Specials can be made to a doctors/dentists prescription on their direct personal responsibility for named patient "off-label" use. It cannot be advertised or branded.
Importation of an unlicensed medicine.
An importer must hold a wholesale dealer's import licence issued by the MCA and must notify the MCA on each occasion that they intend to import the product. Importation may proceed unless the MCA objects within 28 days. The MCA may object because it has concerns about the safety or quality of the product, or because there is an equivalent licensed medicinal product available and it is not satisfied that there is a "special need".
Legal status of medicines
The Medicines Act 1968 and EEC Directive 2001/83 control the sale and supply of medicines. The legal status of medicinal products is part of the marketing authorisation (MA) and products may be available either on a doctor's or dentist's prescription only (POM), or available in a pharmacy without prescription, under the supervision of a pharmacist (P) or on general sale (GSL).
Criteria for switching from POM to P
New medicines are usually authorised for
use as prescription only medicines (POM). After some years' use, if
adverse reactions are few and minor, it is possible that
the medicine may be safely used without a doctor's supervision and be reclassified for
sale or supply under the supervision of a pharmacist (P).
Before a medicine can be switched from POM to P, the MCA must be satisfied that it
a) is unlikely to present any danger to health, even when used incorrectly, without medical supervision.
b) doesn't has an effect that needs monitoring.
d) is not normally prescribed for injection.
Criterion for switching from P to GSL
Pharmacy medicines which have been
safely used for several years may be suitable for general sale. Before a medicine can be switched from P to
GSL, the MCA
must be satisfied that it "can with reasonable safety be supplied
without supervision of a pharmacist".
Reclassifcation procedures
Reclassification normally follows a request from the company which holds a marketing authorisation for it. However, requests can be made by any interested party, such as a professional body, or be initiated by the MCA.
Applications are evaluated by the MCA, with advice from the Committee on Safety of Medicines (CSM). Where it is considered that the proposed reclassification is safe, the proposal is placed on the MCA website for wide consultation.
Advice is sought from the CSM only if a new safety issue is raised during consultation. Following a successful reclassification any other products with the same active substances needs to make a separate application to follow suit.
The 1995 European Licensing System
A European Community marketing authorisation last 5 years and allows medicines marketed in one EC country to be available throughout the European Union.
The system is based around the "centralised" and "mutual recognition" procedures.
European bodies involved in licensing
The European Agency for the Evaluation of Medicinal Products (EAEM) is based in Canary Wharf (London) and co-ordinates the scientific evaluation of the safety, quality and efficacy of medicines throughout the EEC.
The Committee for Proprietary Medicinal Products (CPMP) - is part of the EAEM and pools the scientific expertise of the Member States to give opinions on the marketing of medicinal products.
The centralised procedure
Compulsory for medicinal products derived from biotechnology and optional for other innovative new medicines.
To get a European Community marketing authorisation drug companies submit applications directly to EAEM, who pass it to the CPMP. The CPMP contracts out assessment work to experts in one of the Member States chosen by the applicant.
The CPMP has 210 days to pass an opinion on whether to recommend authorisation to EAEM which in turn has 30 days to forward it to the Commission who makes the final decision on the granting of the European Community marketing authorisation.
The mutual recognition procedure
This applies for all other human medicines and is based on mutual recognition by EU Member States of their respective national marketing authorisations.
To get an existing authorisation recognised across Europe an applicant must submit identical applications to chosen Member States and notify the other Member States that this has happened.
As soon as one Member State decides to evaluate the medicine it then becomes the Reference Member State (RMS) and notifies the other Concerned Member States (CMS) who received the application.
The RMS then sends a decision based on the evaluation to all Member States who have 90 days to recognise it. If the original national MA cannot be mutually recognised by another Member State, the points in dispute are referred to the CPMP for arbitration. The CPMP opinion is forwarded to the Commission who make the final decision.
Once the Commission decision is taken, it is binding on all the CMSs. Other Member States not directly concerned at the time of the decision are also bound as soon as they receive an MA application for the same product.
Monitoring the safety of medicines
No matter how extensive the pre-clinical work in animals, and the clinical trials in patients, certain adverse effects may not be detected until a very large number of people have received the medicine.
The MCA with advice from the Committee on Safety of Medicines (CSM), monitors the safety of marketed medicines by pharmacovigilace.
Pharmacovigilance
Pharmacovigilance is monitoring medicines to identify previously
unrecognised adverse effects to optimise their safe and effective use.
Information from many different sources is used for pharmacovigilance including The Yellow Card Scheme, clinical and epidemiological studies, world literature and the General Practice Research Database.
The MCA/
Committee on Safety of Medicines run the UK's spontaneous adverse drug
reaction reporting scheme (called the Yellow
Card Reporting Scheme) which receives reports of suspected adverse
drug reactions from doctors, dentists, pharmacists and coroners. New
medicines are labelled with a black triangle (
)
symbol.
Optometrists have been contributing to the Adverse Drug Reaction scheme via "yellow cards" since January 1999. These reports which include ocular adverse reactions are collated by the MCA who input the information into a computer system called the Adverse Drug Reactions On-Line Information Tracking (ADROIT). Data collected on ADROIT allows the early identification of ADRs that had not been previously recognised. With this information the MCA can restrict the dose in which a drug can be used or issue special warnings or precautions for use.
The MCA publishes a quarterly bulletin, "Current Problems in Pharmacovigilance" which is sent to all doctors, dentists and pharmacists but not optometrists. This provides extremely useful information on ADRs including ocular adverse reactions and is available on the MCA website at http://www.mca.gov.uk