HIGHLY POTENT APIS
containment , such as a downflow booth , should be used . These are typically equipped with inlet and outlet HEPA filtration , and they use airflow to drive any airborne powders or aerosols containing hazardous material away from operator breathing air space . This secondary level of protection is also beneficial when offloading the media from the chromatography system . The media itself should be contained , but also has the potential to retain potent compound residue . Therefore , the methods and processes used for unpacking and disposal should take this hazard into consideration . As with any method of purification and manufacturing , the waste generated by chromatography will need appropriate management . Incineration is the preferred means of disposal ; the return on investment when purifying waste solvent is negligible relative to the risk of carryover and the low limits required to be considered acceptable for reuse . Although the cost of chromatography columns used for purification can be high , it is possible to regenerate and reuse them across multiple batches of the same product to reduce their direct impact on a product ’ s cost of goods . Compound-specific flushing protocols can be developed to remove residual impurities , but they do not need to be subject to the low product carryover limits when dedicated to a single process . In general , the benefit of retaining multi-purpose process equipment that is dedicated to HPAPI processes is that the cleaning limits will be less prohibitive . Allowable carryover limits are determined based upon an acceptable daily exposure ( ADE ), which will be low for compounds considered to be highly potent . However , when the next product is likely to be a low maximum dosage by virtue of being highly potent as well , it means there is less potential for an amount that exceeds the ADE to be present in a single dose of the next product . At the end of the column ’ s useful life , the medium would be treated in the same way as any other solid waste : packed out under containment and directly incinerated . There will be occasions when chromatography purification is not appropriate for an HPAPI . Crystallisation or precipitation will ultimately be required in order to obtain isolated product for long-term storage and stability . If the solid state characteristics of the HPAPI are important , then the classic considerations of morphic control are necessary , and powder analysis techniques like X-ray powder diffraction , differential scanning calorimetry , particle size distribution analysis and scanning electron microscopy will require specialised containment solutions . As HPAPI drug products are commonly formulated as liquids , this limits the potential for polymorph or other solid-state characteristics to be deemed as critical quality attributes . While every process chemist strives to achieve a ‘ dumpstir-filter ’ process design , even highly selective chemistry steps give rise to by-products , or contain reagents that result in the need for product purification . Within the scale and complexity of HPAPI production , chromatography provides an effective , well-contained and materialconservative approach . •
References
1 : https :// www . marketwatch . com / press-release / high-potency-api-hpapi-market-to-record-a-robust-growth-rate-for-thecovid-19-period-during-2025-2020-09-21
2 : https :// www . prnewswire . com / news-releases / hpapi-and-cytotoxic-drugs-manufacturing-market-3rdedition-2020-2030-301057435 . html
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