Development report

 

The development report is a document that systematically and comprehensively presents the development history of a medicinal product, and which explains the deliberate, organised process in the development of a medicinal product to any external observer (for example the regulatory authorities or inspectors). Nowadays, it is no longer acceptable that medicinal products are developed purely intuitively or by chance and have optimal characteristics at the first attempt. Instead, a logical chain of experiments, investigations, and optimisations must be demonstrated that provides a traceable thread through the sometimes labyrinthine paths of development. It must also be made plausible why, for example, the formulation or manufacturing procedure of the commercial product is comparable with the formulation and manufacturing procedure of the clinical samples.

Although the development report under this name is currently not a legal requirement in the EU or in the US, the authorities expect that "a formalised system exists for collecting the information obtained during development". Independently of the regulatory requirement, with the involvement of industry associations and organisations, it has become standard procedure to summarise this information in a development report shortly before marketing authorisation (see figure 16.F-1).

The development report must contain a list of all the clinical batches used for clinical trials together with a comment on their comparability in terms of formulation, process, specifications, etc. The "history of specifications" must list and justify all changes to the specifications.

It is important to highlight the pivotal studies and the investigational drugs used in these studies. It must also be scientifically justified and proven with data to what extent these clinical samples can be compared with the commercial product, and therefore the extent to which the clinical results are transferable.

If the clinical investigations were performed using a different galenical formulation (for example, capsules) to that intended for the commercial product (for example, tablets), a bioequivalence test is required. In this clinical study, the bioavailability of the commercial formulation is compared directly with the bioavailability of the clinical samples. Particular emphasis is attributed to the quality of the planned commercial product. The batch used for the bioequivalence test is known as the biobatch, and must fulfill certain requirements: The biobatch must be manufactured using the production equipment and, for solid oral forms, must have a minimum batch size of 100,000 tablets or capsules, or 1/10 of the production batch size.

If the commercial product has the same galenic form as the clinical samples, this clinical batch is known as the biobatch, with which the most important clinical study for this product was performed (for example, absolute bioavailability or dose-effectiveness study).

The composition, manufacturing process, analysis data, and stability results of the biobatch are usually in particular demand by the authorities and must therefore be described and commented in detail in the development report.

Although there is no regulatory obligation to compile a development report, the FDA at least still has an idea of what the content of a development report should cover (see figure 16.F-2).