Chromatography in API purification
Adam Kujath , EVP and site head at Sterling Pharma Solutions , looks at an alternative production method for HPAPIs
The highly potent API ( HPAPI ) market is growing rapidly and , according to Kenneth Research , is forecast to be worth $ 33.15 billion by 2025 , more than doubling in size since 2016 . 1 Over 25 % of the total drugs worldwide are currently classified as highly potent , making this one of the most prominent segments of the pharmaceutical industry . 2 This growth has been driven by the potential HPAPIs have in the treatment of serious or chronic conditions , including therapies for cancer , cardiovascular diseases and diabetes . Advanced therapeutics containing HPAPIs can have a significant advantage over standard ingredients and elicit a more targeted pharmacological effect at a lower concentration than traditional alternatives . For the patient , this makes treatment regimes easier to adhere to by reducing the dosage size and minimising potential side effects . For the API manufacturer , it means that the amount of drug substance needing to be produced is significantly less ; however , specialised and dedicated facilities are required for manufacturing .
Handling HPAPIs
The challenges around handling and manufacturing of HPAPIs are well documented . For companies that undertake these activities , an effective containment strategy to protect both the operators and the wider environment is vital .
Engineering controls for containment form the primary safety solution during HPAPI handling but unit operations should also be designed to integrate within multiple layers of protection . This requires specialised air handling and continuous monitoring to ensure that the risk to personnel within a facility is minimised . For companies that manufacture multiple products within the same facility , extensive and effective cleaning and analytical methods are also necessary to reduce the risk of contamination between products , as the permitted carry-over levels are very low . Waste from HPAPI processes also needs to be treated with care to ensure that there is no risk of contamination from a process being released . Again , containment and testing strategies are fundamental to ensure the integrity and safety of operations .
Purification of HPAPIs
In API manufacturing , the preferred method of purification is by using crystallisation , whereas chromatography would be seen as a last resort because it uses prohibitively large volumes of solvent that have to be purified for reuse or disposed of . The equipment needed also has to be large enough to enable the necessary throughput . Alongside the waste solvent , substantial quantities of spent medium will also need to be disposed of .
However , for HPAPI processing , the manufacturing scale is very different . Even for a commercial product , it will be much less than those that are common for a standard API . Batch sizes can be on a gram scale , so the option to use processing techniques like chromatography are more viable , as the volumes of solvent and media , as well as the size of equipment , are all greatly reduced . At every step of a process involving HPAPIs , the risk to operators within the manufacturing facility is a primary concern . Using chromatography means that the highly potent compound is not being handled in powder form and remains in solution throughout . This greatly reduces the risk that it poses to operators , while also minimising material loss . By comparison , even a reasonably efficient crystallisation can result
22 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981