PIC/S to spread process validation and QbD. Brian Carlin emphasises need to build flexibility into design to manage impact of raw material variability through product lifecycle.
SUMMARY of part ii: Emil Ciurczak, President at Doramaxx Consulting:
• Continuous processing: the greatest benefits will be felt by generics firms and those investigating orphan drugs
• Timescales: leaders will continue at the one to two products per year pace for the next several years, then move on to only submitting NDAs with CM at the heart. After that, at first, we will see one or two of the larger generic firms. With success (and having purchased the equipment already), I see more and more getting into the act. Within 10 years, the question will be 1) why did we ever do batch production? And 2) what ever happened to those that didn’t switch?
• Savings: If they “only” use CM for production, I would estimate a 25-35% savings, to be conservative. Expanded to formulation (and clinical trials) to obviate the pain of scale-up, the combined savings could top 50%
• The idea of CM can be merged with 3-D printing and making variable dosage forms, so that is another plus. The “process signature” of a single production stream will also help identify counterfeits and tighten the Supply Chain
Brian Carlin, Director Open Innovation at FMC
• A demonstrated quality culture, however quantified, is a better indicator than compliance with minimum standards
• The potential exists for companies to use their metrics and quality systems to promote themselves in terms of a favourable risk ranking. They might not only have fewer inspections, but, more importantly, they could gain favourable reporting categories for post-approval manufacturing changes
• FDA quality metrics initiative will drive greater scrutiny of the impact of excipient variability
• Supplier QbD may not always be congruent with pharmaceutical product QbD, especially if the pharmaceutical usage is only a small proportion of the market
• Many people fail to understand that fixing everything under their control only makes them more sensitive to raw material variability. The incoming variability will feed forward to finished product quality in the absence of any compensatory mechanisms
• A DOE for filing must be complemented with multivariate monitoring throughout shelf-life. As we move towards a more metrics-driven regime some measure of user-supplier joint due-diligence should be included
Bikash Chatterjee, President and CSO, Pharmatech Associates
• Contract Development and Manufacturing Organizations (CDMOs) whose business model is geared toward partnering with virtual drug development companies are likely to be the first to embrace the core tenets of QbD
• Contract Manufacturing Organisations (CMOs) and Contract Packagers whose primary business model is commercial manufacturing support will be more resistant to the principles of QbD
• The adoption of the Annex 15 guidance by countries subscribing to the PIC/S compliance philosophy means that this new approach to process validation will become the standard for a majority of the world markets
• It is likely larger drug manufacturers in the emerging markets which have the financial bandwidth to absorb the required increase in infrastructure and non-conforming products will be the first to incorporate QbD
Amsterdam, 30 September 2015: CPhI Worldwide, (#cphiww) organised by UBM EMEA, today announces the findings of part ii of its 2015 annual report (entitled: ‘Quality, metrics and continuous processing’) ahead of CPhI Worldwide 2015 in Madrid. Three World-renowned experts – Bikash Chatterjee, President and CSO, Pharmatech Associates; Emil Ciurczak, President at Doramaxx; and Brian Carlin, Director Open Innovation at FMC – look at the implications of QbD, continuous processing, excipient criticality, and process validation on pharma manufacturing.
The overall findings reveal there is clearly now a global commitment to move forward with the principles of QbD, however, the rate of adoption remains highly uneven. At the advanced end of the spectrum there are a limited number of Western manufacturers that are moving towards continuous processing. However, underestimating the complexity of both raw materials and finished products will continue to breed Black Swans, which could be particularly detrimental to continuous manufacture with real time release.
Emil Ciurczak believes that within 10-years all manufacturing globally will be continuous and it is only inertia and the fact that big pharma can still largely charge what they want in the USA that is preventing faster implementation – he warns that those manufacturers that fail to implement change early enough wont see out the decade. The rate of adoption is now accelerating and he states we will see the industry’s leaders producing one or two products per year pace for the next several years, before only submitting NDA’s that include Continuous Manufacturing. He argues it will be at this point that we will see the biggest game changer however, as the largest generics companies (Teva and Sandox perhaps) start purchasing equipment. Following in their lead, the remainder of the market will quickly start investing. Overall, this could bring the cost of drug manufacturing down by as much as 50% if started at the development stage. He concludes that generic and orphan drug companies will see the greatest benefits.
Bikash Chatterjee outlined that, in particular, the gradual integration of QbD principles is going to be transformational over the next few years as companies strive to implement guidelines from the EMA and FDA. In Europe and the US, Contract Development and Manufacturing Organizations (CDMOs) whose business model is geared toward partnering with virtual drug development companies are likely to be the first to embrace the core tenets of QbD. However, contract manufacturers may lag a little in implementation, as they are not forced to embed these processes with new drugs. Now that EMA and FDA guidelines are synergising, PIC/S rollout to 55 countries by 2023 will be transformational in terms of global adoption. In emerging markets, larger drug manufacturers with margin to build in these systems will be first to move across and will benefit from sales into the USA and Europe. For the remainder, we will see an uneven implementation similar to that of GMP in China over the last decade.
Both Emil and Brian Carlin feel the situation with regards to excipients is more complicated, Emil states that continuous processing will not be a factor here and Brian warns of the residual risk from excipient complexity even when using QbD principles. For finished product quality it is the multivariate balance of properties, not just each property separately, that must be controlled. Excipient variability must be addressed. Paradoxically, with fixed formulae and processes, the risk from raw material increases if there are no compensatory mechanisms to stop variability feeding forward. Without joint due-diligence from users and suppliers pharmaceutical ‘black swans’ will continue to impact products.
The experts agreed that global harmonisation, greater raw material understanding, QbD and continuous processing trends will continue. Emil argues in the longer term, this will lead to remarkable innovations such as variable dosage forms when combined with 3D printing. Additionally, the unique “process signature” of a single production stream will also help identify counterfeits and tighten the Supply Chain further – lowering cost, individualising patient dosage forms and improving safety.
Chris Kilbee, Group Director Pharma at CPhI: “Regulation, metrics and quality controls across the pharma industry are evolving, and over the next few years, our experts show that we will be working towards harmonization, improved standards, and in continuous processing, some fairly revolutionary manufacturing techniques. At CPhI Worldwide, we want to make sure we are central to the debate around how pharma is changing and we encourage our experts to use this forum to drive the industry forward. The annual meeting is now a place to not only do business, but also debate how we can partner and improve. By implementing the recommendations from our panel, the pharma industry will advance more quickly, develop better and safer drugs and usher in a new age of lower cost and modernised manufacturing.” The full article will be featured within the CPhI annual report (parts i-iv), which is to be released at CPhI Worldwide 2015 in Madrid, October 13-15th. For more details or to review part ii of the annual report online, please visit http://www.cphi.com/europe/networking/cphi-pharma-insights
Please also join the debate on Twitter and look out for our live tweet chat at CPhI Worldwide 2015 using the hashtag (#cphichat2015) – which will be displayed throughout the event.
-ENDS-
Notes to editors
About CPhI
CPhI drives growth and innovation at every step of the global pharmaceutical supply chain from drug discovery to finished dosage. Through exhibitions, conferences and online communities, CPhI brings together more than 100,000 pharmaceutical professionals each year to network, identify business opportunities and expand the global market. CPhI hosts events in Europe, Korea, China, India, Japan, South East Asia, Turkey and Russia and co-locates with ICSE for contract services, P-MEC for machinery, equipment & technology, InnoPack for pharmaceutical packaging and BioPh for biopharma. CPhI provides an online buyer & supplier directory at CPhI-Online.com.
Help employers find you! Check out all the jobs and post your resume. For more information visit: www.cphi.com The UBM EMEA annual schedule of Pharmaceutical events includes; CPhI Korea (7-9 September, 2015 at the COEX Hall D- Seoul, South Korea); CPhI, ICSE, P-MEC and InnoPack Worldwide (13-15 October 2015, IFEMA- Feria de Madrid, Spain); CPhI, P-MEC, ICSE and BioPh India (1-3 December, 2015 at the Bombay Convention and Exhibition Centre, Mumbai, India); CPhI, P-MEC and Innopack South East Asia (06-08 April, 2016 at the Jakarta International Expo- Jakarta, Indonesia); CPhI, ICSE, P-MEC, BioPh and InnoPack Japan (20-22 April, 2016 at the Big Sight Exhibition Centre- Tokyo); CPhI Istanbul (1-3 June, 2016 at the ICC Istanbul Congress Center, Istanbul, Turkey); CPhI China and P-MEC (21-23 June, 2016 at SNIEC, Shanghai, China). About UBM EMEA UBM EMEA connects people and creates opportunities for companies across five continents to develop new business, meet customers, launch new products, promote their brands, and expand their market. Through premier brands such as TFM&A, Internet World, IFSEC, MD&M, CPhI, Cruise Shipping Miami, the Concrete Show, and many others, UBM Live exhibitions, conferences, awards programs, publications, Websites, and training and certification programs are an integral part of the marketing plans of companies across more than 20 industry sectors.
