The pharmaceutical industry and the regulators need to make a number of improvements if they are to make the shift from just meeting standards to instilling continuous improvement and quality cultures across the board, finds the first part of the CPhI 2016 Annual Report.
Five experts recommend how the industry can improve overall quality and reduce manufacturing errors in the report, which has been published ahead of next week's CPhI Worldwide, which takes place in Barcelona from 4–6 October.
Independent consultant Prabir Basu and Professor Thomas Friedli of the University of St Gallen, Switzerland review a new systems based approach to quality metrics in their article – following the University receiving an FDA grant to undertake this.
The goal is to recommend a measurement system based on St Gallen’s Operational Excellence model, which encourages improved quality rather than lagging indicators that measure symptoms.
The team, which also includes the Dublin Institute of Technology, said these new metrics will ‘help the FDA to establish a clear standard for review and inspection, allowing for a risk-based regulatory approach, transforming quality oversight from a qualitative to a quantitative risk-based process’.
Brian Carlin, Director of Open Innovation at FMC, warned that excipient risk cannot be fully assessed during development, since product and process changes, including scale-up, have the propensity to change the risk profile.
Excipient 'criticality' may be dependent on variations and process changes that occur during manufacturing, which will be unknown at the time of filing, he said.
He added: ‘Continuous monitoring of impact from all excipients throughout the lifecycle is more important than a one-off arbitrary binary classification during development.
'The importance of all attributes and parameters should be evaluated for impact, and re-evaluated as new information becomes available.'
Ajaz Hussain: 'The 'file first, figure it out later' mindset is a fundamental part of the problem'
Emphasising the panel’s concern regarding the need to shift towards quality cultures and away from binary measures of product failure, Ajaz Hussain, CEO at Insight Advice & Solutions, said the 'file first, figure it out later' mindset is a fundamental part of the problem.
He said companies that implement QbD and PAT early in development will see the greatest benefits and have the capabilities to 'file first'.
He added: ‘Broader adoption of PAT-based continuous manufacturing system by brand and by a couple of major generic and CDMO’s should be more prominently evident in the next three years.’
Hussain said the industry is now at a ‘tipping point’ with the first adopters of continuous processing having been included in NDAs, and an excellent opportunity now exists for the manufacture of injectables.
More progress in this area should be expected over the next three years, he said.
However, he argued that the ability to manufacture continuous, while significant, is, in fact, a business decision.
Similarly, Girish Malhotra, President at EPCOT International, said the pharma industry's biggest shortcoming is a lack of manufacturing innovation and while there is much excitement about continuous processing, it must better define what is meant by continuous.
Girish Malhotra: 'The industry must better define what is meant by continuous processing'
In terms of APIs, very few products have the scale to be manufactured truly continuously, he said.
‘Each company producing APIs or its formulations has to justify and use the most cost efficient technology (batch, campaigned batch or continuous) to produce products that are economic and deliver the same quality all the time,' he said.
'Regulators can only regulate and assure product quality. They can suggest the technologies and methods companies should consider for their products. However, companies have to justify use of such technologies. Excellence comes from within companies rather than from outsiders.’
Malhotra suggested that contract manufacturers with similar chemistries would be the first to adopt continuous manufacturing.
The report findings will be discussed further at CPhI Worldwide, said Chris Kilbee, Group Director Pharma at CPhI.
'But what is clear is that while the industry is making significant improvements to overall quality, our experts believe that continuous improvement programmes and on-going analysis are more important to instilling a quality culture than simply striving to achieve minimum regulatory standards,' he said.
'What’s really exciting is that over the next few years we should see a shift towards harmonised standards and more advanced manufacturing.
'By implementing the recommendations from our panel, the pharma industry will advance more quickly, develop better and safer drugs and realise the full potential of lower cost and higher quality manufacturing.'
