EMA says biologics developers need to be extra vigilant

The European Medicines Agency (EMA) stressed the importance of checking if biologic drugs provoke a damaging immune response in pharmacovigilance recommendations​ issued this week, explaining that such products pose more of a risk than traditional chemical medicines.

“Due to their much more complex nature, biologicals pose a greater potential risk of immunogenicity compared to non-biologicals and require specific consideration​” the agency said, adding that extra monitoring may be required and this should be reflected in the associated risk-management plan.

While the agency acknowledged that most biologic induced immunogenicity is short lived and not likely to impact the product’s risk benefit profile it said that “on some occasions, immunogenicity could result in serious and life-threatening reactions.”​

Manufacturing changes​

The guidelines are designed to be read in conjunction with existing pharmacovigilance guideline according to the EMA, which said that the idea is to highlight the additional challenges faced by developers of biologics medicines.

To that end the agency also stressed that, because they are produced in cells rather than being synthesised chemically, any changes to how a biologic could have an impact on its immunogenicity which cannot be predict.

“Most manufacturing changes should result in a comparable product, and the need, extent and nature of non-clinical and clinical comparability studies will be determined on a case-by-case basis​.”

“However, it will not be possible to predict immunogenicity based on physico-chemical/analytical and biological assays alone, and supportive clinical studies will not always be able to detect rare consequences of any altered immunogenicity before approval of a manufacturing change​.”

The EMA advised developers to factor the likely need for additional data in the event of manufacturing changes into product risk management plans.