Radiopharmaceutical Production Product Release STOP
The finished product should be held in quarantine while it is being tested for conformity to pre-determined specifications. When all the necessary requirements of quality assurance for adherence to GMP are demonstrated, the batch is released for patient use. The manufacturer should designate clearly the finished product release authorization (either a designated person or a position). Contents General Aspects of Product Release Authorized Person Example of simple FDG Batch Record Example of detailed FDG Batch Record Transport of the Radiopharmaceutical Product Release STOP
General Aspects of Product Release A product failing to meet the established specifications or other quality criteria (e.g., non-compliance with GMP) must be rejected. Circumstances leading to failed product should be carefully evaluated. The cause of failure should be investigated, and procedures should be established for systematic evaluation of a failed product (a written and approved SOP should be available). Reprocessing may be performed in some instances, but only as per previously written and approved procedures. The reprocessed product must conform to all the specifications prior to approval for release. Frequency of reprocessing must be absolutely minimal. Excessive reprocessing represents a poorly validated process and loss of control in the system. A representative sample(s) of the batch must be set aside for retrospective testing in case of a customer complaint or query related to the product quality. Reserve sample consists of at least twice the quantity necessary to perform all the tests required to determine product quality. The duration of reserve sample retention varies among various GMP guidelines but most require 1 year.
General Aspects of Product Release The final product may be released by the Authorized Person for use once all the following conditions have been met. These conditions are recommended but may not be required. • All the pre-release QC tests on the batch record have been completed and the product meets all the specifications, • The chemist who performed the QC tests has initialed and dated the “performed by” section in the batch record, • The tests results have been verified and the “verified by” section of the batch record has been initialed and dated by a chemist who did not perform the tests, but witnessed the entry. • The Authorized Person has reviewed the document and signed off on the Release Approval lineand entered the date and time in the appropriate place on the batch record. Under certain circumstances, the chemist who performed the synthesis can also act as the authorized person.
Authorized Person • In any GMP laboratory, there must be at least one person who has the authority to release the product for human use (qualified person, authorized person). This is the person who is ultimately responsible to ensure the product conforms to the required quality specifications and is safe to use. This person should have a degree in physical, chemical, pharmaceutical or biological sciences and be familiar with all aspects of GMP and quality management. The qualified person ensures that manufacturing and testing was performed in compliance with GMP standards and the national pharmaceutical manufacturing regulations. The facility management must have confidence the Qualified Person will perform his/her duties responsibly. The qualified person will usually perform other job functions (such as, management of the facility) and is not restricted exclusively to product release. • The qualified person should have: • Formal training in GMP • 2 years practical experience working under GMP license • Authorization by the facility to release radiopharmaceuticals. This may require that the person be a certified Nuclear Radiopharmacist or Pharmacist depending on location and regulations
Simple FDG Batch Record • This is a simple FDG batch record where the FDG is being produced on a commercial FDG synthesizer. The list of materials and supplies is rather short and the specific step by step instructions are contained in a separate SOP for the synthesis of FDG. There is just a checklist for the operator to be sure that everything has been done to start the synthesis. • The last page of the batch record is a blank page where the print out from the synthesizer is pasted. This page is kept with the batch record in storage. • The see the batch record, click on the link. BATCH RECORD
Detailed FDG Batch Record • In the more detailed FDG batch record, there are two sections. The first is the instructions for the procedure in more detail than we saw in the first example and then there is a separate section with the QC tests. These tests must be completed prior to the release of the product with the exception of the sterility test which is done after the fact. • The see the batch record, click on the link. BATCH RECORD • To see the QC test sheet, click on the link. QC TESTS
Transport of the Radiopharmaceutical The transport of the final product will be covered by local regulations. A summary of the IAEA standards for transport of these materials can be found in the following publication. IAEA Publication 1225