Investigational new drugs for PET imaging and human microdosing

¶ … safety as prescribed by the FDA

Extended single dose toxicity testing using rats for PET drugs and Requirements and 2) compliance for using microdosing / Electronic Investigational New Drug Application (eIND) mechanism.

The timing of the study is important (U.S. Department of Health and Human Services Food and Drug Administration et al. 2004). When applying this drug to a human, it is best to administer the new drug in initial low doses in order to assess effect (U.S. Department of Health and Human Services Food and Drug Administration et al. 2004) and to administer it via a physiological route where minimal adverse effects will be felt (ibid.). The drug will be calculated and administered by standardized methods such as that described by the MIRD committee and by the ICRP (U.S. Department of Health and Human Services et al., 2006). The amount of radioactive material administered to human subjects will be the smallest radiation absorbed dose that is practical to perform the procedure whilst providing an adequate diagnostic examination of results for the physician. In other words, (since usually infrequent does to the same patient are ineffective) a repeat-dose pattern (e.g. Of 14-28 days duration; although exploratory studies usually demand 7 days dosage) will be applied where patient will be monitored frequently. Since biological imaging products are often immunogenic and since repeat-doses can generate antibodies which may alter the pharmokinetics, safety, and/or imaging as well as biodistribution properties other agents, the FDA recommends that the particular study or studies incorporate other stated data, such as human anti-mouse body, human anti-humanized antibody and so forth. Calculations will be performed and listed throughout for various reasons including the precaution of anticipating possible changes in dosimetry that may occur due to presence of diseases in organs (U.S. Department of Health and Human Services et al., 2006).

3) cGMP requirements

In order to ensure total safety and efficacy of manufacturing product, the FDA recommends that consideration of biological, physical, and effective half-lives be incorporated into the research design (U.S. Department of Health and Human Services Food and Drug Administration et al., 2004).

Since each product is unique, sponsors are expected to consult with FDA before attempting their product and that numerous studies be conducted on animals / rodents first in order to assess the effects of large mass dose and volume and other effects on tissue and cellular functions as well as all related chemical, and physical effects and so forth. Presenting of study to FDA must include detailed report of study and results that occurred when drug was applied to rodent. Information on anticipated risks must be noted as well as chemistry, manufacturing and controls information that will be employed in Phase 1 exploratory study. Information about pertinent characteristics of patient and attributives of patient as related to drug are also listed. Description of candidate product (all its ingredients) is summarized, as well as intended route of administration, dosage, grade and quality of ingredients, method of preparation of the product, quantitative composition of the product, and brief description of the test methods used to ensure reliability and stability of all constituent elements of the product (U.S. Department of Health and Human Services et al., 2006). This first study will involve limited human exposure and extreme caution.

Most significantly, the study itself has to be based on sound scientific principles with a thorough knowledge of the properties of the chemical, and the potential results on the human subject. Standard clinical safety evaluations will include serial assessment of patient symptoms, physical signs, and clinical laboratory tests amongst other tests monitoring possible adverse effects. These tests will be of sufficient duration in order to catch potential negative effects. Safety hazards for patients and health care workers during and after administration of the radio labeled product will also be identified, evaluated and appropriately managed.

Finally, as prescribed by Section 505(d) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 355(d)), adequate tests must be taken on the drug first before applying to a human individual. The drug must be FDA approved, before sponsor is allowed to proceed.

4) micro dosing: its benefits.