During the production of a biological medicinal product in Australia, the curren
ID: 277318 • Letter: D
Question
During the production of a biological medicinal product in Australia, the current cell culture medium has become unavailable and a new and different cell culture medium must be introduced. Discuss the effects of changing cell culture conditions and the potential impact on the biological production process. Would this be of concern to a regulator? What might be needed to adequately characterise the first step of the biological production process? What could be the consequent impact on the clinical trial product and the clinical trial endpoints
Explanation / Answer
There are several concerns, first of all if the groth medium is changed there may be minor problems or no problems at all. If the expression host is changed there will be a definite huge problem. As per the question and my understanding it is asking more of a change in the growth media rather than change in the expression host.
If the medium is definite known synthetic medium or its complete compostion is known and which is similar to earliar medium used then there wont be any problem. If the media componants have changed a little bit definitely expresson host starts behaving differently. For example if the media componants changed the folding and glycosylation patterns may change which adversely affect the functionality of a given protein drug. If the media componants have changed we may have to change our entire harvesting, down stream processing, purification processes and analytical techniques. Sometimes we have to reinvent some of the process to exactly produce the molecule as with the earlier media componant system.
Yes regulators definitely object for new media change, they will ask for entire clinical trials to be redone or produce data which proved to be safe production with new media componants. To adequetely charecterise the production process the first step we need is completely charecterising the new media componants, test and ascertain its compatiblity or compare with the earlier line production process. Additionally we have to check wether the given molecule production is safe, compatible and properly produced as per earlier standards. This is nothing but reinventing the entire process. Structurally if any thing changed in the molecule like its folding pattern, peptide compostion, glycosylation, its half life, its immunogenecity, its efficacy and many other componants definitely show an effect on clinical trials. If any of the parameters have changeg we may have to do entire clinical trial process again, many parameters of clinical trial endpoints may change, for example if aminoacid composition of a given peptide changes (eventhough functionally same), it may affect pharmacology of that peptide and may have sideeffects, these all processes are time consuming and financial burden on the company and competetors may outcompete by the time we reenter the market again.
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