EMEA Issues Guideline on Biologic Production Changes
A new European Medicines Agency (EMEA) draft guideline details factors taken into consideration when the agency determines whether clinical studies are necessary to evaluate a biologic drug product after its manufacturing process has changed.
The guideline, which will take effect in November, replaces the EMEA’s previous draft guideline on the comparability of biotech products, known as CPMP/3097/02, the agency said.
“If a manufacturer can provide evidence of comparability through physicochemical and biological studies, then nonclinical or clinical studies with the post-change product are not warranted. In other cases, additional nonclinical and/or clinical data will be required,” the EMEA said.
Under the new draft, the need, extent and nature of nonclinical and clinical comparability studies will be considered on a case-by-case basis, based on various factors, including:
- Process complexity, the nature of the change, the potential impact on the molecule structure and on the final product profile;
- The nature and extent of differences demonstrated by the physicochemical and quality-related biological characterization, including product-related substances, impurity profile, stability and excipients. Thus, well-characterized differences may provide a background for a rational and focused approach with respect to the need for nonclinical and clinical studies; and
- Product complexity, including heterogeneity and higher order structure, and the availability, capabilities and limitations of analytical tests. If the analytical procedures used are not sufficient to discern relevant differences that can impact the safety and efficacy of the product, additional nonclinical and/or confirmatory clinical testing may be necessary.
The new draft, “Guideline on Comparability of Biotechnology-Derived Medicinal Products After a Change in the Manufacturing Process: Non-clinical and Clinical Issues,” can be accessed at www.emea.europa.eu/pdfs/human/biosimilar/10169506enfin.pdf.