General regulatory requirements for biopharmaceuticals

A full discussion of the general regulatory requirements for biopharmaceuticals is beyond the scope of this work but clear guidelines have been laid down in the FDA Points to Consider documents and in the European Community guidelines (Table 6.1), and these documents should be consulted for detailed information on the relevant test programmes.

In general the regulatory bodies call for

• full characterization of the starting materials: gene, genetic construction and host cell.

• full details of the establishment of the banks of production cells, of procedures used for their maintenance and of their stability.

• full details of the production process and the stability of the production cells during the process.

• full details of extraction, purification and characterization of the product.

• evidence of consistency of manufacture.

The guideline documents expand on these requirements and propose techniques that are acceptable and how these should be operated and the results interpreted.

Specific safety issues with animal cells

One of the risks of using cells for the production of biological products is that because they share many of the same biochemical capacities as the patients who will eventually receive the products they are also subject to some of the same pathological events including infection by viruses and the development of oncogenic changes. In principle, the agents causing such events could be transmitted from the production cells to the patients receiving the bioproduct. For this reason, in the early days of the use of cells as substrates for vaccine production, the FDA ruled that only normal cells derived from normal tissues could be used.