Quality control tests radiopharmaceutical

The quality control tests have been categorized for PET radiopharmaceuticals into two groups those with nuclides with ty2 > 20 min and those with nuclides with ty2 < 20 min. In the case of the former, each production on a given day is considered a batch while in the latter group, a batch is defined as... 

In the above section, requirements for compounding of PET radiopharmaceuticals have been presented. In this section, the methods of quality control tests for these products are briefly described below. Since PET radiopharmaceuticals are short-lived, some lengthy tests cannot be performed prior to release for human use and so they are performed within a short time after the release. 

The manufacturing and handling of radiopharmaceuticals is potentially hazardous. The types of radiation emitted and the half-lives of the radioactive isotopes are parameters contributing to the level of risk. Particular attention must be paid to the prevention of cross-contamination, to the retention of radionuclide contaminants, and to waste disposal. Special consideration may be necessary with reference to the small batch sizes made frequently for many radiopharmaceuticals. Due to their short half-life some radiopharmaceuticals are released before completion of certain Quality Control tests. In this case, the continuous assessment of the effectiveness of the Quality Assurance system becomes very important. 

One of the inherent problems in the production of short-lived radiopharmaceuticals is the (X)nsistent delivery of usable amounts of labeled product. In a clinical cardiac study using the PETT system and relabeled palmitic acid, 20-25 mCi is normally injected into a patient. The amount of activity injected depends on the patient s physical characteristics and the desired scan time. The lower limit of usable amount of activity is 15-17 mCi however, this amount of riC-palmitate often produces borderline statistical information and makes determination of the infarct size diflBcult. Animal studies usually require lower amoxmts of labeled product however, in the case of some dog studies, the amount of activity required is the same as for a human preparation. In our experience covering over 220 syntheses for patient and animal studies during the past two years, C-palmitic acid has been prepared in usable amounts in over 85% of the cases. Several modifications and additional quality control tests have been added to the previously described synthesis to increase the reliability of the procedure (32-34). 

Table 3 Quality control tests required for radiopharmaceuticals manufactured by different methods...

The quality control of radiopharmaceuticals labeled with short-lived radionuclides has to rely on indirect methods for the identification of the compound. Direct methods such as nuclear magnetic resonance (NMR) and infrared spectroscopy cannot be used. Some tests, such as measurement of pH and LC-analysis, can be performed before the radiopharmaceutical is released for use. The radiopharmaceutical is mixed with authentic reference substance and if... 

The quality control of the final product must be carried out before release of the batch (except for the sterility and the endotoxin tests for extremely short-lived radionuclides). Consequently, all procedures must not only be very fast but also very accurate, and in all cases it is very important to have a properly established quality assurance system that might permit parametric release of the produced batches. The quality control assays that must be carried out in the radiopharmaceutical includ the following ... 

All quality control procedures that are applied to nonradioactive pharmaceuticals are in principle applicable to radiopharmaceuticals. In addition, tests for radio-nuclidic and radiochemical purity must be carried out. Furthermore, since radiopharmaceuticals are short-lived products, methods used for quality control should... 

In contrast, ACR emphasizes the quality control, calibration of the equipment, and technology used in the procedures, and accordingly has developed three modules - module 1 for oncology, module 2 for brain, and module 3 for heart. A PET center must apply for all modules that are performed at the facility. For accreditation, the facility is required to submit information on the quality control and quality assurance program, data collection, reporting, radiopharmaceuticals procedures, and laboratory safety, along with chnical and approved phantom images. So, all equipment in a PET center is required to be calibrated and tested for accurate functionahty for accreditation by ACR. 

Short-lived radiopharmaceuticals have to be manufactured, quality-tested, and dispensed within a short time, adding constraint on safety procedures. In order to comply with the strict requirements of GMP, special methods for synthesis and in process quality control have been developed, assuring high quality of radiopharmaceuticals, without actually testing sterility and apyrogenicity before dispensing the labeled product. 

Due to the short half-life of certain radiopharmaceuticals it may be necessary to despatch the products before all the tests are completed. This does not reduce the need for a formal recorded decision to be taken by an authorised person as to whether or not the product should be released based on the production and quality control data available at the time. Specifications should define at which stage of testing a decision on release may be taken. 

In some situations, for example with very short-lived radiopharmaceuticals, conditional release before all QC tests are performed is necessary. As a consequence, process validation is important An immediate recall procedure must take place, when product quality is found to be insufficient Stock preparations usually undergo an extensive analytical control (see Sect. 34.9.2) and remain in quarantine until the QC is fuUy completed (see Sect. 34.9). The release is based on the assessment of the document control in combination with the analytical quality controls. During release, final reconciliation takes place. For certain preparations (e.g. aseptic preparations) also the results of monitoring of production conditions are included. 

QC on Ready-for-Use Products from a Manufacturer. These radiopharmaceuticals are to be administrated to the patient without further preparation. As the manufacturing is inspected by competent authorities in order to ensure a high quality of the production process, the QC in the hospital in most cases can be reduced to control of transport documents, labels, and radioactivity. Tests on radionuclidic or radiochemical purity are normally not required. 

---