Mindset Change Needed to Drive Continuous Manufacturing Adoption

Conferences focused on continuous solid-dosage manufacturing aim to spread the word about technical capabilities and alleviate perceptions of regulatory uncertainty.

Continuous manufacturing of pharmaceuticals could reduce the inefficiencies found in batch manufacturing. It creates an opportunity to implement more modernized manufacturing processes, which lead to better quality end products. This technology could also help prevent drug shortages through faster and more responsive supply chains. Continuous technologies offer the potential to replace the outdated "quality by testing" regime currently employed by the industry with a more robust "quality by design" system, which is possible because of the improved process understanding and  robust control strategies gained through continuous processing, said Bayan Takizawa, co-founder and chief business officer at CONTINUUS Pharmaceuticals, at a conference session on continuous manufacturing at INTERPHEX on March 21, 2017.

Industry, academia, and regulators have spent significant time and money over the past decade to develop pharmaceutical continuous manufacturing, and commercial approvals have been the fruit of this labor. Many other companies have developed the required technical capabilities and are poised to implement them, but seem to be in a “wait and see” mode, commented Doug Hausner, associate director at the Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), at the INTERPHEX session. Most of the technical barriers have been overcome by the industry as a whole, he noted, but having the right people, knowledge, and equipment at an individual company can be a challenge. A “big picture” mindset, rather than evaluating the advantage of the new technology on a product-by-product basis, is needed to promote high-level support for capital expenditures, said Hausner. The perception of regulatory uncertainty, particularly in large, important markets, such as Europe, is another limiting factor.  

Regulatory agencies offer support
FDA has been quite clear on its support of continuous manufacturing over the past several years. FDA’s message has been consistent that it sees no regulatory hurdles for implementing continuous manufacturing, it supports the implementation of continuous manufacturing using a science- and risk-based approach, and it sees continuous manufacturing as consistent with FDA’s quality initiatives (1,2).

Other regulatory bodies have perhaps not been as vocal in their support of continuous manufacturing as FDA has been, but the European Medicines Agency (EMA) has begun to express support and recently clarified its position, providing further technical specificity. At the 3rd FDA/PQRI Conference on Advancing Product Quality (March 22­–24, 2017), EMA’s Dolores Hernan noted that the current regulatory framework allows continuous manufacturing, and although specific guidelines are not available, the existing ones are supportive of this approach (3).

Both FDA and EMA recommend communicating with the agencies early in development (2,3). “The toolbox is out there, and EMA and FDA want you to come talk with them to show them you understand these new tools as you go to use them,” notes Hausner.

Focused conferences spread the word
Several conferences in 2016, such as the International Society for Pharmaceutical Engineering (ISPE)’s Continuous Manufacturing Conference, the FDA-American Institute of Chemical Engineers (AIChE) Workshop on Adopting Continuous Manufacturing, and the 2nd International Symposium on Continuous Manufacturing of Pharmaceuticals organized by the Massachusetts Institute of Technology (MIT) and the Continuous Manufacturing and Crystallization Consortium (CMAC), have worked to increase understanding and to promote adoption of continuous manufacturing.

In May 2017, the global International Institute for Advanced Pharmaceutical Manufacturing (I2APM) is hosting the Emerging Pharmaceutical Manufacturing Summit, May 8–9, 2017 in Malta, to bring together first- and second-wave technology adopters, regulators, and academics. C-SOPS, one of the founding groups of I2APM and one of the event organizers, hopes that European regulators, in particular, will benefit from seeing the examples of commercially approved implementations of continuous manufacturing.

The United States Pharmacopeial Convention (USP), in collaboration with C-SOPS, hosted a workshop in the US in 2016 on continuous manufacturing, one of the outcomes of which was a new expert panel that is now working to standardize terms and characterize materials specific to what it is calling PCM [pharmaceutical continuous manufacturing]. USP and C-SOPS signed a memorandum of understanding in February 2017 as part of their commitment to collaborate and work to make PCM more widely available (4). USP is hosting a workshop in India on May 16–17, 2017 to introduce PCM to Indian pharma companies, particularly generic drug companies.

References

  1. S. Chatterjee, “FDA Perspective on Continuous Manufacturing,” Presentation at IFPAC Annual Meeting (Baltimore, Jan. 2012).
  2. D. Hernan, “Continuous manufacturing: Challenges and opportunities. EMA perspective,” 3rd FDA 3rd FDA/PQRI Conference on Advancing Product Quality 22-24 March 2017. 
  3. USP, “Exploring Continuous Manufacturing Technology and Applications in the Pharmaceutical Industry,” (March 13, 2017), http://qualitymatters.usp.org/exploring-continuous-manufacturing-technology-and-applications-pharmaceutical-industry  accessed March 24, 2017.
  4. J. Woodcock, “

” Presentation at MIT-CMAC ISCMP (Cambridge, MA, May 20, 2014).