Non-clinical Post-Marketing Commitments for newly licenced pharmaceuticals.

摘要

There are clear minimum requirements for non-clinical (toxicology) studies which are needed prior to human exposure to a potential new pharmaceutical and additional studies are needed in an ongoing manner to support clinical development and marketing [ICH, 2009. ICH M3(R2) Non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals (CPMP/ICH/286/95). Adopted June 2009, effective December 2009.] The pharmaceutical industry is under increasing pressure to reduce costs and reduce, refine and replace the use of animals, as far as possible. Hence any increase in regulatory requirements for non-clinical safety data could have a significant impact both on the economic and ethical considerations of drug development. It is, therefore, of interest that further non-clinical studies are required by the Regulatory Authorities for a small but increasing proportion of drug product applications at the marketing approval/data review stage. These studies are known as Post-Marketing Commitments (PMCs). Available information on non-clinical PMCs was collated using drug product information from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA), resulting in a combined data set of 162 studies. Non-clinical PMCs comprised 9.8% and 6.5% of total PMCs for products authorised by the EMEA (Centralised Procedure) and FDA, respectively. Non-clinical PMCs increased with increasing date of approval, despite increased regulatory information available to guide Applicants. Furthermore, the increase reflected an increased proportion of applications with non-clinical PMCs, not an increase in overall numbers of applications. There was no clear correspondence between the publication dates of relevant guidelines and increases in specific non-clinical PMC study types, when the data were analysed by non-clinical study category, target population/indication or compound class. Possible exceptions were some photocarcinogenicity and juvenile toxicity studies. For many non-clinical PMCs relevant guidance existed in the concurrent regulatory information. Hence these PMCs could have been predicted based on known pharmacology, indication and route/duration of administration. Conclusion. Some increases in non-clinical PMCs were attributed to increased non-clinical data requirements from the Regulators. However, strategic deferrals by the Applicant, unintended omissions due to poor regulatory intelligence and overall differences in risk perception between Regulators and Applicants account for a significant proportion of the non-clinical PMCs.