Drug product thresholds

Threshold Maximum daily dose of drug product Threshold limit based on total daily intake (TDI)... 

TABLE 8 Thresholds for Impurities in a Drug Product According to ICH Q3B... 

U.S. Food and Drug Administration (FDA), Extra 6 Safety thresholds and best practices for extractables and leachables in orally inhaled and nasal drug products, PQRI Leachables and Extratables Working Group, available http //www.pqri.org/pdfs/ LE Recommendations to FDA 09-26-06.pdf. 

Table 3.1. Various ICH Thresholds Regarding Degradation Products in New Drug Products as Stated in the Current ICH Guidelines Q3B(R)...

Table 8.1 ICH guidelines for reporting, identification, and qualification thresholds for impurities in drug substances and drug products [7, 8]...

In general, the detection and identification of impurities present in API and formulations play an integral role in the drug development process and methods need to be developed to adequately resolve these species and quantitate them. The International Conference on Harmonization (ICH) [3] has published a guidehnes on impurities in new drug substances and new drug products (see Table 8-1). The acceptable limit of the impurities in drug substances is dependent upon the maximum daily dose and the quahfication threshold however, lower thresholds are sometimes deemed necessary if the... 

Table 2 ICH Q3B(R) reporting and identification thresholds for impurities in drug product...

THRESHOLDS FOR REPORTING OF DEGRADATION PRODUCTS IN NEW DRUG PRODUCTS... 

In ICH Q3B(R) (see Appendix), the thresholds for the drug product for reporting, identification, and qualification of the degradation product are specified. The suggested thresholds are shown in Tables 9-11. 

The terminal half-life is a hybrid parameter, and its determinants need to be acknowledged. It is either a hybrid PK parameter determined by both clearance and distribution of the substance or, when there is a flip-flop, a PK characteristic of the drug product depending on bioavailability factors (rate and extent of absorption). In this latter case, the terminal half-life does not reflect the intrinsic rate of substance elimination. Whatever the biological factors controlling the terminal half-life, T1/2 should be considered to select an optimal interval between dose administrations. This is clear if one considers a threshold plasma concentration required for AMD efficacy a long terminal half-life will result in a longer time for plasma concentrations to decline to the threshold concentration. 

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