Although radiopharmaceuticals have no intrinsic pharmacological actions, they are regarded as medicinal products because of their use in vivo. Accordingly, they must comply with all the requirements applicable to conventional medicinal products in addition to those specific of their nature as radioactive substances.
As a radiopharmaceutical manufacturing laboratory, IRAB guarantees all the studies and controls required to verify the quality and the safety of its radiopharmaceuticals, complying with the strictest quality and safety standards established by the national and international regulatory bodies.
In this regard, quality assurance and control constitute an integral part of overall radiopharmaceutical practice. Radiopharmaceutical controls are based on the physicochemical, biological and radiological aspects inherent to radiopharmaceutical manufacture.
Physical state of the radiopharmaceutical: Some radiopharmaceuticals are found in all three physical states (solid, liquid, gas), and in some cases the physical form is decisive for their biological behavior. The organoleptic properties may exhibit changes as a consequence of the radiation emitted by the radiopharmaceutical.
pH: The optimum pH of an injectable preparation, which is the most common form of radiopharmaceutical, is 7.4; however, this value may differ significantly according to the stability of the radiopharmaceutical preparation. Nevertheless, in radiopharmaceuticals for injection, the pH value is not of capital importance, partly because of the high buffering capacity of blood and the small injection volumes normally used.
Tonicity of injectable preparations: The isotonicity of an injectable preparation is the equality between the osmotic pressure of the solution for injection and the blood serum. The tonicity of a solution for injection can be established from cryoscopic measurements, vapor pressure measurements and conductometry methods.
Radioactive concentration: Radioactive concentration is the activity present per unit volume. This concentration is used to calculate the volume of radiopharmaceutical needed to perform a given exploratory test. The activity of the dose must be strictly that which is required to perform the test. The standard units of radiopharmaceutical activity are megabecquerels (Mbq) or millicuries (mCi). Devices called activimeters or dose calibrators are normally used to measure such activity.
Chemical purity: Chemical purity determines the proportion of molecules present in a specific chemical form. Impurities must never exceed the authorized limits. Chemical impurities might not be toxic, although when administered with the radiopharmaceutical they can modify its chemical characteristics and therefore its biodistribution. Analytical techniques such as high-performance liquid chromatography (HPLC), gas chromatography, etc. are some of the techniques commonly used for radiopharmaceutical chemical purity control.
Radionuclidic purity: Radionuclidic or radionuclide purity is defined by the proportion of total activity present in the form of the specific radionuclide. The main problem with impurities is that they unnecessarily increase the dose of radiation absorbed by the patient. The presence of radionuclide impurities is therefore very important in relation to the dosimetric safety of the patient. Radionuclidic purity control is performed by emission spectrum analysis or by controlling the disintegration half-life.
Radiochemical purity: Radiochemical purity is the proportion of radionuclide present in a radiopharmaceutical preparation in a specific chemical form (the radiopharmaceutical’s). Labeling yield refers to radiochemical purity. Factors such as manufacturing time, temperature, incubation time, oxidative processes, radiolysis, etc., can affect the product radiochemical purity. Radiochemical purity is determined using analytical methods that can separate the different radioactive chemical species.
Specific activity: The specific activity of a radioactive compound is the activity of the radionuclide of the compound in question per unit mass of the compound. In other words, it does not consider either activity caused by contaminating radionuclides different from the radionuclide of the compound in question or mass caused by the presence of other different compounds. Specific activity is expressed in units of activity per mass unit (MBq/mg, Ci/g, etc.).
Toxicity: The possible toxicity of radiopharmaceuticals is one of the parameters that must be controlled, despite the fact that these compounds are frequently inert and are used at extremely low concentrations.
Sterility: Sterility is the absence of germs and pathogens such as bacteria, fungi and other microorganisms. Sterility is an essential requirement in preparations intended for parenteral administration.
Apyrogenicity: A pyrogen is any agent capable of inducing a febrile response and/or organic shock. In this regard, radiopharmaceuticals must guarantee the absence of any possible pyrogens. Pyrogens are highly varied and include lipoteichoic acid, peptidoglycan, endotoxins and certain viral and fungal particles, steroids and enterotoxins. Sterility does not guarantee the absence of endotoxins. The apyrogenicity of products for injection is ensured by employing apyrogenic substances particularly in the water used for manufacture, as well as by taking the required preventive and control measures during the manufacturing process.