Principles that guide us in our Process Development programs:
Select a solid form (salt or neutral) of the target substance that offers the desired solubility, stability and solid state properties early on. Such a selection process involves a salt and a solid state screen of selected salt/neutral.
Prioritize the development of the final process stages early on. Later process stages are more likely to impact heavily on the products impurity profile and other critical quality attributes (CQA), such as solid state properties.
Identify impurities found in the target substance and trace these back to their points of origin. This information provides guidance in the process development work, which is aimed at controlling and reducing these critical impurities (early part of QbD). In later stages of the development program these critical process parameters are formally identified and acceptable process ranges are set. This is the basis for Quality by Design (QbD).
Often speed of delivery is a priority in the beginning of the development program. Producing the early clinical supply using a first manufacturing process and later on a switching to a more effective manufacturing process is often a preferred strategy. When such a switch is planned for it is important to avoid changes in the target substance qualified impurity profile and solid state properties. Changes in the earlier parts of the process are often possible without affecting the CQA’s of the product (se bullet 2).
Principles that guide us in our Analytical Development programs:
Assign assay (strength) of a well characterized reference standard. Use 1H NMR assay determination for comparison of assigned (calculated) assay.
Early on, develop and validate a suitable analytical method for quantifying related substances and determination of assay.
Work closely with the process chemist and identify impurities in target product and track these to their origin.
Identify critical impurities in key raw materials that may carry to target product such as homologues and isomers and set relevant specifications limits.
A forced degradation study provides pathways for degradation of the target product. This information is used in the development of analytical methods as well as gives important clues to likely process impurities in the target product. Also the information is useful in the development of suitable packaging methods for the target product.
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Coulometric Karl-Fischer Titrator
Phone: +46 8 554 422 50
SE-151 02 Södertälje
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SE-151 38 Södertälje
Phone: +371 67 490 881
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Syntagon Baltic SIA
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