Below are some examples of where and why having a broad knowledge base from the very outset of product development is significantly helpful in plotting the most efficient route to gaining solid information about the product.
In terms of the product, prior knowledge about the cell line used for manufacture and the possible structural features that gain importance on this basis is significant. For example, biopharmaceutical products and biosimilars engineered in an E. coli cell line require in vitro re-folding through disulfide bridging and therefore the disulfide bridge pattern of such products gains particular importance.
Also important is knowing that that certain excipients can interfere with analytical methods. This can range from the obvious (e.g. amino acids in formulation buffers will need to be removed prior to amino acid analysis) to the less obvious (e.g. polysorbates and antifoams can interfere with chromatography-based analyses).
Correct method choices
Knowledge regarding which methods can be applied to analysis of a particular product to gain the required information is also very helpful in providing data in an efficient manner. In practice, the list of applicable methods chosen for analysis of any product should be data-led rather than decided theoretically.
At BioPharmaSpec ,we generally apply a range of methods (i.e. all those required by ICH Topic Q6B) to a product during an initial Pilot Study and subsequently choose the most appropriate applicable methods for the product based on the data obtained. We know that there are knowledge-based generalities that apply and can help with efficiencies. For example, secondary and tertiary structure analyses generally require product in concentrations of >1mg/mL. Therefore, for products such as Erythropoietin where the Final Product is formulated at ~35µg/mL, it is not possible to get such data for the Final Product. Analyses of these molecules would have to be performed at the Drug Substance stage.