For the tradition-bound biopharma industry, resisting change is no longer an option

“For nearly half a century the pharmaceutical industry has lagged other industries in terms of productivity, efficiency and, some might argue, innovation,” wrote Bikash Chatterjee. “The excuse was that, as a regulated industry, any flexibility to implement improvements is limited, and compliance is of paramount importance.”

Chatterjee, president and CSO of Pharmatech Associates, made these remarks in the CPhI Annual Industry Report, a collection of expert essays released in conjunction with the CPhI Worldwide conference, held recently in Frankfurt, Germany.

Reluctance to change was a common undercurrent in numerous essays in this year’s compilation. As Chatterjee and several other commentators observed, however, not changing is no longer an option. Instead, pharma companies must embrace change to succeed whether that means  figuring out commercial models to sell into emerging markets, improving manufacturing efficiencies/continuous manufacturing, or embracing six sigma.

Chatterjee in his essay, “An Argument for Change – The Promise of the Next Decade,” highlighted a number of paradigm-changing events that are driving the pharma industry’s evolution:

  • the rise of emerging markets, with both positive impacts (sizeable new market opportunities, access to educated but inexpensive labor) and negative ones (quality issues);
  • regulatory compliance convergence, including PIC/S (the Pharmaceutical Inspection Co-operation Scheme) which should lead to increasing awareness between compliance and product quality;
  • the adoption of the elements of risk management throughout the development and commercial process which should allow the industry to move away from a framework focused on documentation and traceability to one based on the understanding of the product and process;
  • the transformative impact of data and data analytics;
  • the rise of e-clinical platforms, diagnostics and digital health opening up new routes for clinical trial design and speeding up go/no-go decisions.

Economics driving change

Digging deeper into the topic of economics driving change, Girish Malhotra, president at Epcot International, explored what combination of sales of new innovative drugs and generics would be required every year to sustain a 6.5% CAGR for the pharma industry into 2022.

A key point in his essay,” An Alternate Look at the Pharmaceutical World and Drug Affordability,” was  that companies have tremendous opportunities to increase their sales if they can figure out how to make their drugs affordable for patients in emerging markets.

Malhotra looked at a number of options available to cut costs without cutting quality, including lower manufacturing and regulatory costs and improvements in manufacturing technologies.

“Economies of scale and better manufacturing technologies can make drugs affordable and increase sales,” he wrote.” However, to achieve all this will require business model review and change. It is not an easy task for an industry that has not aggressively embraced change and innovation.”

Minzhang Chen, CEO, and Sam Tadayon, executive director, both of Sta Pharmaceutical, explained in their essay, “Continuous API Manufacturing – It’s Time Pharma Went with the Flow,” that the surge in interest around continuous processes in the pharma industry emanates from a number of factors. These include the availability of more expertise in the area of flow chemistry over the last decade and the need for the industry to develop safer, faster and more sustainable processes, with higher quality and less expensive products.

The industry is running two broad types of continuous processing, in finished formulation and API manufacturing, they observed. While noting that continuous processing in finished formulations with the potential of on-demand dosing is “extremely exciting,” they specifically looked at the improvements that flow chemistry can make in the area of developing and manufacturing of active ingredients.

They explained that when transitioning from batch to flow, timing matters. Limited changes can be made to APIs currently produced at the commercial stage due to regulatory issues. Similarly, switching at phase III would likely result in approval delays. For flow chemistry to deliver on its huge promise, pharma and CDMOs need to build the platform into the phase I process R&D of innovative API programs, they wrote.

Brian Carlin, excipient iconoclast, foresees a significant evolution in the excipient industry. He argued in his essay, “Commodity Inactive Ingredients? Not So Fungible, Not So Inactive,” that the future is in multivariate continuous monitoring. “The current practice of univariate change control is not predictive and will yield passing results until sudden failure,” he said.

Carlin also wrote that the industry needs new excipients to be developed but that this will require regulatory approval mechanisms “other than the current indirect route of incorporation in a finished product.”

Lessons from Amgen’s journey

In his essay, Ajaz Hussain, of Insight, Advice & Solutions, explored what is required from companies to succeed on their transformational journey. He pointed out in “Self-authorship of Performance Standards is Necessary to Break the Pharmaceutical 2-3 Sigma Barrier” that a few companies in the pharma-biopharma sector are already at or very close to six sigma 3.4 dpm (defects per million). He shared key lessons from the experience of one such company, Amgen.

Exploring Amgen’s journey, Hussain drew parallels between adult human development and change within companies. He explained that leaders at Amgen worked to overcome organizational and individual immunity to change. Ultimately, the company progressed on its journey to 3.4 dpm using the following steps:

  • analytical characterization of raw materials, manufacturing processes and products (both in development and commercial settings);
  • the will of management and their involvement to identify, track and control variation via process capability assessment;
  • continuous monitoring to ensure robust analytical methods, manufacturing processes and products;
  • training, qualification, certification and mentoring support to ensure flawless execution;
  • a sharp focus on supply chain.

‘An entirely different looking industry’

In “What changes are in the Future of Pharma?”, Emil Ciurczak of Doramaxx Constulting underscored the point that ultimately economics is the largest driving force for change. In today’s environment, companies are facing price controls and are under tremendous pressure to make less expensive drugs. Yet cutting quality is not an option.

Ciurczak encouraged companies to adopt PAT (process analytical technology) even if they are currently heavily invested in traditional batch manufacturing. Even small steps, such as qualitative examination of all incoming raw materials (both excipients and APIs), can pay big dividends, he said, whether by allowing the operators to better estimate the mixing times or by saving time in the QC lab.

He predicted that larger companies will move to their own QbD/CM processing in the future or outsource to CMOs that have QbD/CM capabilities

Smaller companies and generic companies may have no choice but to shut down, merge with others so that they can afford/support QbD/CM, or ally with a larger pharma company in the production of off-patent brands.

Ultimately, he predicted that “there will be an entirely different-looking industry in a decade: there will be fewer companies and the only ones making a profit will be the ones who understand and properly implement QbD.”

For additional insights from CPhI Worldwide, including a copy of the author Kate Kuhrt’s presentation, “API Sourcing & Manufacturing Update,” click here.