The European Medicines Agency (EMA) made the statement in a reflection paper intended to clarify the variability allowed when sourcing starting materials and intermediates from living organisms.
“Variability in sourcing and initial manufacturing steps has traditionally been allowed in contrast to the well characterised biotechnological products of recombinant origin for which the declared manufacturing process starts from a unique and well identified cell bank system”, the EMA wrote.
Before allowing such variability the EMA wants details of the manufacturing processes. Companies should list and justify any different purification steps, process conditions, and equipment used by suppliers.
The EMA uses heparin as an example. “The marketing authorisation dossier should cover the whole manufacturing process starting from the sourcing of the mucosa. Aspects with potential impact on product quality and safety needs to be presented in sufficient detail”, the EMA wrote.
Details requested by the EMA include species and country of origin, traceability from abattoirs, and confirmation that the animals used are fit for human consumption. The other examples given by the EMA are urine- and plasma-derived products.
Variable suppliers
While acknowledging the need for “some flexibility within the 'one process = one product' paradigm” the EMA wants to define what is acceptable. By allowing some differences the EMA hopes to make it easier for manufacturers to find multiple suppliers and minimise the risk of drug shortages.
“These first steps of collection, testing and pre-treatment of the starting material may be carried out by different suppliers who could apply different processes to obtain an 'early intermediate'”, the EMA wrote.
When using suppliers with different processes manufacturers should make sure their own production steps are robust enough to ensure the drug is the same, regardless of the intermediate used.
“It should be shown that comparable products are consistently obtained in terms of relevant quality attributes irrespective of the process applied. Discernible differences in quality attributes should be discussed and justified in terms of product quality”, the EMA wrote.