Radiopharmaceuticals guidances

Changes to the final intermediates and the resulting API will be covered in the BACPAC II guidance document. Postapproval changes affecting peptides, oligonucleotides, radiopharmaceuticals, natural materials, and semisynthetic APIs are not covered by BACPAC at the present time. 

Submitting Supporting Chemistry Documentation in Radiopharmaceutical Drug Applications. Guidance for Industry. Food and Drug Administration. November 1, 1991. 

Notes for guidance on the Clinical Administration of radiopharmaceuticals and use of sealed radioactive sources, ARSAC Dec 1998. 

USP-NF monographs include assays and various analytical methods—identification, dissolution, content uniformity, etc. USP-NF also provides guidance and standards on biotechnology, radiopharmaceuticals, pharmacy compounding, and pharmaceutical waters. General chapters outline requirements for microbiological, biological, chemical, and physical tests and assays. 

The FDA also published in the Federal Register a draft guidance for industry entitled, PET Drug Applications - Content and Format for NDAs and ANDAs (March 10, 2000 65 Fed.Reg. 13010). It is intended to assist manufacturers of certain PET radiopharmaceuticals in submitting NDAs or ANDAs. Comments were solicited until a final rule is adopted. The guidance details the criteria for when to apply for an NDA or an ANDA and what to include in the application. 

Whereas readers are referred to these specific documents for details available on the Web site http //www.fda.gov/cder/fdama, some of the specifics are briefly mentioned here. The essence of this guidance emphasizes the importance of the overall quality assurance in manufacturing a PET radiopharmaceutical. All equipment and measurements used in the manufacture must be validated. The areas and hoods in which PET radiopharmaceuticals are manufactured must be run in a sterile condition. The personnel responsible for the manufacture must be well trained in the methodology, and an appropriate number of personnel are required in a production laboratory. Each step of the production must be verified and records must be maintained. The sterility and pyrogen testing of the finished product must be performed by appropriate methods. If a PET radiopharmaceutical is to be commercially distributed, appropriate containers and techniques must be adopted for safe shipments. 

Good pharmaceutical manufacturing practice applied to the hospital preparation of radiopharmaceuticals (1977) Dept, of Health and Social Security, notes for guidance issued by the Medicines Inspectorate, London... 

Radiopharmaceutical preparations are preparations containing one or more radionudides. They may be formulated in any of the pharmaceutical formulations covered in this guide and the general and specific guidance should be followed at ail times, but considerations must be given to the spedal requirements of radiation work. 

A radiopharmaceutical is a medicinal product which achieves it purpose, at least in part, by virtue of its radioactivity. It may be formulated in any of the pharmaceutical presentations covered by this Guide and the general and specific guidance given should be followed as appropriate. The radioactivity may necessitate modification of this guidance in some respects. 

In the manufacture of sterile radiopharmaceutical the need for modifications of guidance given elsewhere is likely to be most apparent. Non-radioactive components should be prepared as described in Section 9. It may be necessary to handle radioactive materials in a contained work station operated at an air-pressure below that of the room in which it is sited. Air admitted to the room should still have passed through terminal filters of appropriate porosity so that with the operator present and work in progress, the required class conditions (see Section 9) are maintained at the point of greatest risk, where products are exposed. All operations up to the stage of sterilization should be carried out in a manner which minimizes microbial and particulate contamination. 

Anyway, several guidance documents are available, which can be used as standards. The European Association of Nuclear Medicine (EANM) issued guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals [15, 16]. In these guidelines GMP and radiation safety requirements are interpreted for radiopharmaceuticals not intended for commercial purposes. 

It is not easy to interpret aU above mentimied legislatimi and to give uniform guidance for each country and each situatimi. The determination of adequate quality assurance measures, for example the GMP-classificati(Mi of the clean room, should be the result of a risk assessment [20]. Table 15.2 gives a practical overview of the applicable guidance and the appropriate quality assurance level when preparing radiopharmaceuticals. 

Table 15.2 Overview of the guidance and main quality assurance issues of the different steps in the extemporaneous preparation of radiopharmaceuticals ...

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