PHARMACEUTICALS
‣ Next to a reliable process , a reliable supply chain for all of the registered starting materials must be established . There have been numerous efforts to decrease the attrition rate of drug projects on their way to launch , but it has remained high , putting all development efforts or investments dedicated to the manufacture of a specific drug at considerable risk . Regulatory bodies like the US FDA have recognised that the risk to product quality and its own workload of regulatory oversight is linked to the conservative production methods of the pharmaceutical manufacturers . In 2004 , the FDA started to exhort the industry to modernise its manufacturing methods and in 2017 , the Centre for Drug Evaluation and Research edited a guideline on the advancement of new technologies . 5 , 6 The European Medicines Agency installed an ‘ Innovation Task Force ’ to foster development of new technologies in pharmaceutical development and manufacture . 7 In 2021 , the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use published Guideline Q13 on continuous manufacturing . 8
New manufacturing technologies
To be successful , technologies typically employed by a CDMO must support :
• Fast process development
• Scale-up with minimal process changes
• Quick , well-controlled manufacturing
• Fast , accurate product characterisation The rise of continuous manufacturing technologies ( continuous reaction , continuous work-up , all monitored and controlled by continuous analytics ) over 15 years has been marked by numerous publications but comparatively few implementations . Given the seemingly striking advantages of continuous processing that have been reiterated in the technical literature , one has to invoke non-technical reasons for CDMOs to be reluctant to develop and apply them . There are many . In the view of those who have invented a new drug candidate , new , ‘ unproven ’ technologies like this may :
• Pose a risk to reliable material supply
• Limit the choice of CDMOs and increase the risks associated with transferring production to other manufacturers
• Pose a risk of the CDMO applying its own IP rights in producing the material , thus limiting the ability of the innovator to have the material produced at a chosen location
• Complicate the technical documentation of the manufacturing process in their filing documents CDMOs , in their turn , have pointed to the following hurdles to implementation :
• The physical existence of conventional processing equipment and the knowledge and skills developed by manufacturing staff to set up , clean and operate equipment
• An overwhelming majority of recipes and procedures in the literature perform chemical reactions in batches . With few exceptions , library syntheses are also performed in batches 9
• Perceived additional efforts in time and money to develop a process , set up and operate a continuous manufacturing unit So , while there have been numerous examples of innovations related to ‣
New APIs act at low doses , calling for proper containment to handle them in a safe way
18 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981