Draft guidelines come six years after a drug manufactured in transgenic goats, ATryn (antithrombin [recombinant]), gained approval in Europe. Since then regulators on both sides of the Atlantic have approved similarly produced drugs but the European Medicines Agency (EMA) still wants vigilance.
“Since experience with the technology is relatively limited when compared to the longer established methods, applicants are advised to be appropriately vigilant towards transgenic system-specific aspects such as development genetics…and their impact on product reproducibility”, the EMA wrote.
Producing proteins in transgenic animals creates new quality challenges, such as husbandry issues, as well as those common to cell-based expression. In some areas these differences will make ‘classical’ GMP (good manufacturing practices) difficult to apply and as such the EMA allows some flexibility.
“Whether performed in accordance with GMP or with a defined quality system…the early steps of the manufacturing process should be well controlled by the application of suitable in-process controls [and] provide a well-defined starting material suitable for subsequent processing”, the EMA wrote.
It is these early manufacturing steps that are most alien to traditional methods of drug production and the EMA devotes much of the document to generating and maintaining the animal population.
“Impact on animal health due to expression of the recombinant protein should be considered since expressed recombinant proteins may have potent effects on the production animals”, the EMA wrote.
Once the animal has expressed the active pharmaceutical ingredient (API) the downstream process is similar to traditional manufacturing, although certain contamination concerns are more pronounced.
“Steps should be taken to minimise the bioburden associated with [microbial] contaminants and they should be removed or reduced to inconsequential levels as soon as possible after the start of downstream processing. Monitoring for them will be required”, the EMA wrote.
The EMA is accepting comments until November 30.