A drug can be approved for marketing in either a centralized or
decentralized way. For the centralized procedure of approval, the European
Medicines Agency (EMEA) was established in 1995, which controls the
evaluation and supervision of medicines for human and veterinary use.
Once a drug is considered to be safe, of high quality, and efficacious, a single
market authorization is granted for the product for the entire EU. In the
decentralized procedure, an application for drug marketing is made to one
member state that approves or disapproves it after review. The applicant
state can then present the authorization to other member states for regis-
tration to market the drug in those states.
Directive 91/356 EEC establishes the principles of good manufacturing
practices (GMP), which apply to drug manufacturing at the industrial level
as well as compounding in hospitals. These guidelines are parallel to those
of the CGMP of the USFDA. For each approved radiopharmaceutical for
marketing, a summary of product characteristics (SPC), equivalent to
package inserts in the United States, must be included.
The European Pharmacopoeia specifies the characteristics of all radio-
pharmaceuticals in monograph forms, regarding radionuclidic and radio-
chemical purity, pH, sterility, pyrogenicity, and so on. It is mandatory in drug
product manufacturing in the entire EU and equivalent to the USP in the
United States.
Within the EU, it is the responsibility of the radiopharmacist to ensure
the quality, safety, and efficacy of a radiopharmaceutical if it is intended for
human administration. Similarly, the nuclear physician is responsible for the
administration of a radiopharmaceutical to the patient and the clinical care
of the patient for any adverse reactions thereof. Claims may be made
against any adverse reaction for up to 10 years after the event, therefore
the patient’s and preparation’s records must be maintained for this length
of time.
Clinical trials are conducted by qualified clinicians based on protocols
approved by an ethics committee in each institution. Data are collected on
pharmacokinetic characteristics, clinical efficacy, safety, and the like for a
particular indication of a disease, which are then submitted for marketing
authorization. Any modification in a product or its administration requires
a new clinical trial.
The radiation aspects of radiopharmaceuticals are regulated by directives
from the European Atomic Energy Community (EURATOM). Initial
Directives 84/466 EURATOM, and 84/467 EURATOM were based on the
recommendations of the ICRP, and mandate regulations for radiation pro-
tection for patients, radiation workers, and the public. Because the ICRP
revised the basic standards for radiation protection in 1996, Directive
84/467 EURATOM was repealed and substituted with Directive
96/29/EURATOM. Upon further revision of the basic standards by the
ICRP, Directive 96/29/EURATOM has been amended by 97/43
EURATOM, and finally Directive 84/466/EURATOM was repealed. These
296 16. Radiation Regulations and Protection