HIGHLY POTENT APIS in the loss of 10 % or more of the product to the mother liquor , as well as mechanical loss on the surface of the filter . For low-volume , highvalue compounds like HPAPIs , this loss means additional handling problems for the waste streams and the need to clean hazardous material from the equipment . Many classes of compound that are determined to be HPAPIs are challenging to crystallise and may be amorphous , leaving no alternative but chromatography . In antibody-drug conjugate development , a cytotoxic synthetic warhead is bonded to the linker molecule . These long-chain conjugates can be of relatively large relative mass , resulting in a sticky , oily compound that will not crystallise . Similarly , large metal complexes including platinum or palladium can also be difficult to crystallise .
Chromatography is often more effective in removing free residual metals from the product . It has the versatility in application for a wide variety of molecules , and does not depend on physical morphology and large differentials in solvent solubility . Chromatography processes have the ability to be highly selective , with a clear separation while affording high recovery . This is paramount when dealing with HPAPIs where the value of the material is high and handling high volumes increases the risks . Liquid chromatography methods used in purity analysis of an HPAPI during development will generally provide a good starting point to develop the solvent and column conditions for the separation . Because the HPAPI is in solution , handling is far less complex than when dealing with solids , limiting hazardous powder transfer steps . The use of process analytical techniques ( PAT ), such as inline ultraviolet detectors , on the column outlet should be employed to further reduce the risk of containment loss , which can occur with discreet sampling methods . Ultimately , obtaining highly purified fractions of product , a final crystallisation can be designed to maximise product recovery and focus on isolation performance only .
Additional considerations
The chromatography system itself is generally considered to be contained , as the equipment is to be closed and under pressure . However , to ensure safety in the potential event of a breach in containment resulting in liquid aerosolisation , secondary
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