33 An Industrial Perspective: Practical Stages in Model Development

Ferdie Rombout

N.V. Organon, 5340 BH, Oss, Netherlands

There are differences in the implementation of the population approach in industry when compared to the population approach in an academic setting. These differences range from the time pressure to the regulatory requirements. This presentation describes the process involved within our company to design, evaluate and report population pharmacokinetic and pharmacokinetic/pharmacodynamic studies. A phase IIa study will serve as an example.

Some of the items presented are

Population approach and GLP/GCP

In N.V. Organon the population approach is the responsibility of the Department of Drug Metabolism and Kinetics which is subjected to GLP. Population approach and GLP means defining the complete data acquisition, evaluation and reporting process at forehand.

Population approach and time compression

Due to the nature of population analyses, the evaluation is almost always on the critical path. This means that there are problems to be solved. These problems are mainly related to the hardware, software, logistics and the evaluation process (model development).

Scientific versus industrial needs, a constant balance

Studies are not always performed because of scientific interest, this means that especially due to lack of time, scientific interest can not always be satisfied. This also means that if a population approach is performed, somewhere there should be point to be satisfied with the results of model building. For this reason clear objectives should be stated.

From data acquisition to reporting: Practical stages in model development

In view of the above mentioned reasons, the stage of data acquisition to reporting should be as short as possible, without loosing interesting/important facts. Standardization (although seemingly impossible for the model development) should be a goal. All the steps starting with writing the protocol via data checking, structural model building, covariate model building, validation, reporting and review are all of same equivalent importance and should be well documented.

Population approach and regulatory requirements

Regulatory requirements for the process of population analyses are not well defined, neither is the place of population approach within the requirements for a new drug approval. This might be partly due to the nature of population approach itself, standardizing the process will increase its regulatory possibilities.