New EC GMP regulations for radiopharma
The updates to the annex are intended to make it compliant with GMP Part II, which laid out additional requirements for actives substances used as starting materials.
In addition the EC has sought to bring the regulations up-to-date with advances in the manufacture of radiopharmaceuticals.
An initial draft was published for public consultation in December 2006. This process has now been completed and companies have until March 1 2009 to become compliant with the new requirements.
The regulations are broken down into subcategories including quality assurance, personnel, production and documentation. These are intended to provide the necessary regulation to prevent cross-contamination, the spread of radioactive material and ensure the quality of the product.
Quality assurance is particularly important in the manufacture of radiopharmaceuticals as the half-lives of some mean they need to be administered shortly after production. Consequently there is not enough time to test the product.
To maintain high standards the regulations insist on rigorous record keeping and for the principles of qualification and validation to be applied, details of which can be found here.
A sizeable proportion of the regulations are to ensure that radioactive material does not spread beyond its confines. These provide guidance on the use of air filters, equipment and the appropriate level of environmental cleanliness for the type of operation.
Underlying all the regulations is the need for accurate, up-to-date documentation of procedures. Manufacturers must establish specifications for raw materials, labelling and packaging materials, critical intermediates and the finished radiopharmaceutical.
Specifications must also be put in place for any piece of equipment that could critically impact on the quality of the finished product.
The cleaning, sanitisation, sterilisation or maintenance of equipment should be documented to show the product name, batch number, date and time of the activity and signature for the persons involved in these activities.
Documents must be kept for a minimum of three years, unless a different timeframe is specified by national laws.
Retention to ensure accountability extends to keeping sufficient samples of each batch of bulk formulated product for at least six months after expiry of the finished medicinal product.
Samples of starting materials, excluding solvents gases or water used in the manufacturing process must be kept for at least two years after the release of the product. This period can be shortened if the material has a period of stability of less than two years.
Annex 3, the complete document covering GMP requirements for the manufacture of radiopharmaceuticals, can be found here.
