CPhI Worldwide experts propose new FDA Quality metrics system and recommend Critical Formulation Attributes

SUMMARY of part i:

Girish Malhotra President at EPCOT International:

• The pharmaceutical industry’s biggest shortcoming is a lack of manufacturing innovation
• Continuous manufacturing needs a proper definition, and is very unlikely for nearly all APIs (as volumes are too low) and the business case is not justified
• Contract Manufactures, with similar chemistries, will be first with continuous manufacturing

Ajaz Hussain, Insight, Advice & Solutions LLC

• Human factors need to be more closely considered in designing manufacturing processes – using behavioural economics will help improve practices Industry is often trapped in a “file first, figure it out later mindset” and simply try’s meet standards not improve quality
• 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.
• Continuous manufacturing of injectables is a major opportunity to overcome the risk of drug shortages.
• There is a key need to advance educational and training programmes in India and China to advance PAT and continuous processing here

Prabir K Basu, Consultant, Mt. Prospect, IL, U.S.A. & Thomas Friedli, Professor, Institute of Technology Management, University of St.Gallen, Switzerland

• Metrics used to measure the performance of a pharmaceutical operation should be systems oriented – and not lagging indicators measuring symptoms (e.g. batch failure rate etc)
• The important components of a true operational excellence program (OPEX) are continuous improvement, management commitment, and employee involvement. In principle, there is an excellent match of the key components of OPEX and those of an ideal quality system. Therefore, it makes tremendous sense to develop and integrate the metrics for OPEX implementation with an appropriate metrics for “Quality” for pharmaceutical manufacturing operations
• Team proposes new metrics that 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 Open Innovation at FMC

• All excipients are potentially critical,especially when subject to cumulative changes throughout the product lifecycle
• A quality culture will seek to control excipient-related special cause variation before an out of specification excursion. Most excipient-related impact on manufacturability will not be known at time of filing.
• 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.

Amsterdam, September 27, 2016: CPhI Worldwide, (#cphiww) organised by UBM EMEA, today announces the findings of part i of the 2016 CPhI Annual Report on potential new approaches to improve quality and manufacturing process in pharmaceutical production ahead of CPhI Worldwide 2016 in Barcelona. Five World-renowned experts – Ajaz Hussain, Girish Malhotra, Brian Carlin, Pabir Basu & Thomas Friedli – propose improved methods to how we evaluate and consider quality in the pharmaceutical industry, making a number of key recommendations.

The overall findings reveal there are a number of improvements industry and the regulators can and should make to shift the industry from just meeting standards towards instilling continuous improvement and quality cultures across the board – which the panel predict will vastly improve overall quality and reduce manufacturing errors.

Prabir Basu, independent consultant and Prof Thomas Friedli of the University of St Gallen 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, state that 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’.

Furthermore, Brian Carlin, Director of Open Innovation at FMC warns that excipient risk cannot be fully assessed during development, as 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 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’.

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 LLC states that the “file first, figure it out later” mindset is a fundamental part of the problem. He believes that 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.’

Ajaz believes 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 and we should expect more progress over the next three years. However, he argues the ability to manufacture continuous, while significant, is, in fact, a business decision.

Similarly, Girish Malhotra, President at EPCOT International, suggests that whilst there is much excitement around continuous processing, we must better define what it is we mean by continuous – as in terms of APIs, very few products have the scale to be manufactured truly continuously. There simply isn’t the volumes needed and the industry greatest shortcoming is its overall record of manufacturing technology innovation. He commented: ‘All said and done each company producing APIs or their 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. 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 with in the companies rather than outsiders.’

Chris Kilbee, Group Director Pharma at CPhI: “The findings in this report will be disused further at CPhI Worldwide during the CPhI annual report media debate, but what is clear is that whilst 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. What’s really exciting is that over the next few years we should see a shift towards harmonised standards and more advance 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.”

For a copy of the full articles in the CPhI Annual Report 2016 – released at CPhI Worldwide in Barcelona (4-6^th October) – please visit http://www.cphi.com/europe/cphi-annual-report

Corporate Comm India(CCI Newswire)