CPhI Worldwide Report States The Current Drugs Pipeline Is Discouraging And Slowing Simple Manufacturing Innovations

Experts predict PAT/QbD and CM adoption may take ten years, with smaller generic players to drop out of the market if unable to innovate in time

Amsterdam, 19^th October 2017: CPhI Worldwide – held in Frankfurt, October 24-26 and organised by UBM – announces the findings of part ii of the 5^th edition of the CPhI Annual Report, which focuses on the immediate and long-term trends in pharmaceutical manufacturing and ingredients.

The second part of the report is being launched ahead of CPhI Worldwide, taking place next week (October 24-26, 2017), with the full report unveiled to more than 42,000 executives during the event. Three manufacturing and ingredients experts have given their perspectives on both the near- and long- term trends – Emil Ciurczak, President at Doramaxx Consulting; Brian Carlin, the excipients iconoclast, and Girish Malhotra, President at EPCOT International.

The overall findings reveal that the trend towards the increased use of modern manufacturing processes and quality systems is occurring very slowly – with the current small molecule drugs pipeline not yet possessing the economic models and incentives to stimulate faster adoption (e.g. changing to continuous processing is expensive and may not deliver advantages over batch for certain drug classes). A lack of excipient innovation and multivariate analysis are also identified as a potential growing risk. Collaboration to develop new excipients will be needed, however, biologics are the most likely to support the development of new excipients, given the high product value and susceptibility to excipient impact on quality.

Girish Malhotra, President of EPCOT International, feels that the global pharma industry is now at a critical point in its history and needs to adopt new business models for the next century. “The current approach of developing new drugs for rare and orphan diseases, and for only the most affluent patient cohorts, is actively discouraging manufacturing innovation” he warns. Adding, “these newer drug are produced in smaller qualities and often feature high margins and profits – meaning the incentive to improve manufacturing processes is not there.” Malhotra presents a number of methods whereby big pharma can sustain long-term profits, open up access to emerging markets by improving manufacturing efficiencies, and therefore reduce their total costs. Most importantly, this will increase the number of patients that can benefit.

“Making drugs affordable is the best long-term way to improve the total sales in the developing countries. Because of the income differences between developed and developing countries, the differences in drug processes will remain for the foreseeable future. Economies of scale and better manufacturing technologies can make drugs more affordable and increase sales. However, to achieve all of this will require a business model review and substantial change. This is not an easy task for an industry that has not aggressively embraced change and innovation. Their focus has always been on new drug development and marketing – drug affordability is an unknown area”, commented Malhotra.

Emil Ciurczak, President at Doramaxx Consulting forecasts that it might take as long as a decade for the industry to see the full potential of its impact – but resistance is futile and, ultimately, only those that adopt QbD/PAT and continuous manufacturing (CM) will survive. However, should the regulators (EMA and FDA) harden their positions and force the industry to work towards a QbD and PAT deadline, we will see rapid purchasing of new equipment, with a race to compete like has happened with serialisation in the last few years.

“Large companies will naturally be the first movers, followed in parallel by their strategic outsourcing partners, and this will become an established practice over the next three-years. For generic companies, and particularly smaller ones, there is an existential debate pending. Do they A, close; B, merge with or acquire other small companies to have the critical mass to invest; or C, as is happening now, partner with the larger Pharma companies to produce their off-patent, older (but still in-demand) brands. In ten years, the market will be made of fewer, but larger companies, and the profit generators will be the ones that understand and properly implement QbD”, commented Ciurczak.

Brian Carlin, Excipient Iconoclast, echoed Emil’s thoughts and warned that the industry needs to move to smarter control of its processes, and increased use of PAT, if excipients (amongst other factors) are not to introduce critical and often unforeseen risks into products. He argues that the industry as a whole must now embrace multivariate control over the next couple of years, as current practices are not predictive and will yield passing results until sudden failure. “Investment in PAT and data mining will involve additional costs, but this must be balanced against the increasing Cost of Poor Quality (COPQ) associated with regulatory initiatives on quality metrics and quality culture” added Carlin.

Biologics, he argues, may be the exception to the rule and is the area most likely to support the development of new excipients. Overall, Carlin believes regulators need to provide approval mechanisms for excipients, as the current indirect route of approval via incorporation in a finished product is inimical to innovation. Instead, collaboration between users and the excipient developers must be sought to reduce the commercial risk of new excipient development.

Orhan Caglayan, Brand Director Europe, UBM EMEA: “As the industry’s annual meeting point, the discussions next week at our eponymous global event will be vital in furthering development throughout the industry. From the experts’ point of view, long-term success is dependent on companies adopting modern manufacturing processes, including QbD and PAT, to reduce inefficiencies and excipient risks. We produce this report each year to help our exhibitors and the wider industry to stay ahead of trends and prepare for change, opportunities, and threats. It also helps our attendees to be better informed during discussions with partners at CPhl Worldwide.”

For a copy of the full articles in the CPhI Annual Report 2017 – released at CPhI Worldwide in Frankfurt (24-26^th October 2017) – please visit http://www.cphi.com/europe/cphi-annual-report

-ENDS-

Appendix

Girish Malhotra, President, EPCOT International

• Based on the sales increase from 2008 to 2016, we can speculate that the projected 2022 sales will mostly come from the developed countries, rather than the developing countries. Orphan drugs (less than 200,000 patients per disease) are going to be an ever-increasing source of revenue and as a result
• Brand pharma have shifted their focus from drugs for the masses, to orphan drugs. It is well known that orphan drugs increase revenue dramatically as they are very highly priced and also highly profitable. New drugs are being introduced continuously but most are only marginally better than the drugs already on the market and are equally expensive.
• FDA’s application, review and approval process of NDA and ANDA is based on analysis and re-analysis of the application, and this process is similar to a manufacturing process. FDA and regulators have suggested that companies should incorporate QbD (quality by design) practices in their manufacturing processes. Perhaps the regulators should show the industry how incorporating QbD practices in their own workings will improve application approval quality leading to reduced approval time and associated costs.
• Command of processes produces quality products from the start rather than producing products through repeated analysis (aggravation)
• Continuous improvement effort is needed. The industry should not be told to improve their practices, the effort should come from within (quality by desire) as they reduce drug approval time.

Emil W. Ciurczak, President at Doramaxx Consulting

The industry cannot just jump to continuous manufacturing without “prior knowledge” of PAT principles, which lead to QbD concepts (including lifecycle concepts, supply chain control, LEAN, six sigma). Continuous Manufacturing is the peak of the pyramid and, like the roof of a building, it needs the proper foundations

The chief driver for continuous manufacturing adoption will actually be cost drivers, coupled with stricter regulation (meaning corner cutting alone will not achieve desired profit results)

Regulatory reform could facilitate rapid change – i.e. if the US FDA and EMA were to announce that they would enforce the two parts of cGMPs (PAT/QbD) by 2022

• Larger companies will move to 1) their own QbD/CM processing or 2) outsource to CMO’s that are QbD/CM capable in the next three years.
• Smaller/generic companies may have difficulty engaging the personnel/technology needed to move to successful QbD/CM manufacturing, so they will have three options: 1) close (there is no law forcing them to stay in business), 2) merge with one or more small companies, so they can afford/support QbD/CM, or 3) (happening now) the larger Pharma companies engage and support one or more smaller companies to produce their off-patent, older (but still in-demand) brands.

Only the companies making a substantial profit will be the ones who understand and be able to properly implement QbD.

Brian Carlin, Excipient Iconoclast

• The future is multivariate continuous monitoring. The current practice of univariate change control is not predictive and will yield passing results until sudden failure. Future use of multivariate continuous monitoring requires the ability to capture and analyse relevant data, consistent with the trend towards greater use of Process Analytical Technologies (PAT)
• It is hard to predict when there will be a consistent global regulatory approach to science/risk based quality. Multiple conflicting requirements from various jurisdictions will continue to add uncertainty and cost in the near term
• Biologics is the area most likely to support the development of new excipients given the high product value and susceptibility to excipient impact on quality
• The industry needs new excipients to be developed but this will require regulatory approval mechanisms other than the current indirect route of incorporation in a finished product incorporation, and collaboration between users and the excipient developers to reduce the commercial risk.
• Diversification of the excipient industry into two groups (‘novel’ and ‘commodity’) may be accentuated by the ability and willingness of the excipient suppliers to provide data as the information value of the excipients continues to increase

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, North America, Korea, China, India, Japan, Southeast Asia and the Middle East, and co-locates with ICSE for contract services, P-MEC for machinery, equipment & technology, FDF for finished dosage formulations, InnoPack for pharmaceutical packaging and BioPh for biopharma. CPhI provides an online buyer & supplier directory at CPhI-Online.com.

For more information visit: www.cphi.com

The UBM annual schedule of Pharmaceutical events includes: CPhI, ICSE, P-MEC, FDF and InnoPack Worldwide (24-26 October, 2017 at the Messe Frankfurt – Frankfurt, Germany); CPhI & P-MEC India (27-30 November, 2017, BEC and BKC Exhibition and Convention Centres – Mumbai, India), Pharmapack Europe (7-8 February, 2018 at the Paris Expo, Porte de Versailles – Paris, France); CPhI, P-MEC and Innopack South East Asia (27-29 March, 2018 at the Jakarta International Expo – Jakarta, Indonesia); CPhI, ICSE, P-MEC, BioPh and InnoPack Japan (18-20 April, 2018 at the Big Sight Exhibition Centre – Tokyo, Japan); CPhI, ICSE, FDF and InnoPack North America (24-26 April, 2018 at the Pennsylvania Convention Center – Philadelphia, USA); CPhI and P-MEC China (20 – 22 June, 2018 at SNIEC – Shanghai, China); CPhI Korea (28-30 August 2018, COEX, Seoul, Korea); CPhI Middle East & Africa (3-5 September, 2018 at the ADNEC – Abu Dhabi, United Arab Emirates).

About UBM

UBM 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.