Advancing Collaboratively in Changing Times

"Collaboration," "Innovation," "Quality," "A new way of doing"...these were all buzz words that spanned most sessions of the three-day PDA/FDA Joint Regulatory Conference, held Sept. 8–10 in Washington, D.C.

Keynote speaker Stephen Ostroff, MD, Acting Chief Scientist, U.S. FDA, kicked off the conference, stating that this is a period of “rapidly expanding discoveries and opportunities” with scientific breakthroughs happening at an extremely rapid pace. This in turn, is driving—at unprecedented speed—innovation and the development of novel medical products. Furthermore, since FDA is charged with the regulatory oversight of medical products, this rapid period of change calls for continuing adaptation of the Agency’s role in bringing innovative medical products to market. He then cited a few examples of such cutting edge technologies: the application of genomic sequences to diagnose and treat health conditions, development of 3-D printing to facilitate personalized medical care, application of stem cells in regenerative medicine, and biomonitoring with cell phones and other mobile devices.

The Agency, Ostroff further said, is going through a period of transformation in which innovation, collaboration and the global nature of business are key considerations. FDA’s goal, he said, is to facilitate bringing to market innovative medical products that can benefit the public, as rapidly as possible. Breakthrough therapy (BT) designation, fast track designation, accelerated approval and priority review designation are examples of the Agency’s expedited review programs for drugs and biologics (1). In addition, FDA and the Centers for Medicare & Medicaid Services (CMS) recently established a pilot program for concurrent review (2) to expedite patient access to safe and effective medical devices.

These new approaches at the FDA, he explained, require a collaborative mindset for bringing together expertise from the industry, academia, government and elsewhere. Although this is not a traditional model for the Agency, he indicated that the Office of the Chief Scientist is uniquely positioned to facilitate such collaboration and innovation through public/private partnerships.

Prior to Ostroff’s talk, PDA Chair Hal Baseman, Chief Operating Officer, ValSource, PDA President Richard Johnson and meeting co-chair Monica Caphart, Deputy Director, Division of Human Resource Development, Office of Regulatory Affairs, FDA, opened the event. Their remarks reiterated the overarching theme of the conference and the pharmaceutical world’s current state of affairs. That is, assuring total product lifecycle quality with customer-focused outcomes using innovative approaches and state-of-the-art science and technology as scientific discoveries and innovation happen at incredible speed.

This theme was expanded upon in the session following Ostroff’s talk, “Analytics & Manufacturing of the Future.” Madhu Balachandran, Executive Vice President, Amgen, presented certain perspectives on next generation manufacturing (NGM) and how NGM can play a role in avoiding drug shortages. He walked the audience through a NGM approach used at Amgen to mitigate a drug shortage. The approach included four main elements— Prevention (through a Quality System), Technology (to minimize damage to product), Inventory (to protect against surprise variations) and Diversification (to avoid single point of failure). [Editor’s Note: For more on Balachandran’s perspective, please see p. 36 of the full PDA Letter].

Mansoor Khan, PhD, Director, Division of Product Quality Research Programs, CDER, followed Balachandran’s talk with a presentation on some quality considerations for parenteral drug products, from a CMC perspective. He provided an overview of field alert reports and recalls on parenteral drug products during recent years and highlighted factors that were common to many recalls. Khan also pointed out the establishment of CDER’s Emerging Technology Team (ETT) to assist innovative manufacturers better navigate the regulatory process. This team, he said, would facilitate the inspection and review of manufacturing facilities where novel pharmaceutical product development and production approaches are involved.

Continuing the focus on quality, on the second day of the conference Maria Crowe, President, Lilly Manufacturing, Eli Lilly, presented an example of Eli Lilly’s “quality journey” as the company prepared to achieve its “safety first, quality always” motto. She discussed how Lilly applied a comprehensive framework for their manufacturing and quality management system—establishing integrated standards to document expectations, and define business processes for delineating how the work gets done are key components of this framework. The Lilly quality journey, said Crowe, has led to a focus on “continuous improvement, integration, and sustainability.”

This was followed by a presentation from Janet Woodcock, MD, Director, CDER, who talked about how pharma’s evolving landscape has warranted changes within the FDA. Some of the drivers of this change include increasing global manufacturing, expansion of contract manufacturing and just the sheer increase in volume of new drug products. She also talked about the progress of the “quality culture” at FDA. It aims to meet the needs of the evolving pharma landscape paradigm and enable the industry to stay the course on their quality journey of shifting from a “compliance-driven” to a “quality-driven” approach of doing business. Woodcock cited the recent implementation of expertise-based team reviews at CDER and the establishment of CDER surveillance programs as examples.

The last day of the conference gave a human element to the often high-level concepts discussed with a patient perspective from Terri Sarisky, Director, Quality Systems and Compliance, Merck. She walked the audience through her journey following her mother’s diagnosis of glioblastoma multiforme (GBM). Sarisky said that it “took a village” to enable her mother’s recovery stressing that the collaborative approach from doctors, nutritionists, medical radiologists and other caregivers was key for her mother’s survival.

The conference attracted 852 participants. It gave ample opportunity to attendees for professional networking and also for hearing from a diverse group of stakeholders including regulators, the regulated industry and patients, all steps in the pathway to working together collaboratively to tackle a changing industry.

References

1. Guidance for Industry Expedited Programs for Serious Conditions – Drugs and Biologics, U.S. Food and Drug Administration: May 2014 www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM358301.pdf
2. U.S. Food and Drug Administration. “FDA-CMS Parallel Review.” www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/ucm255678.htm (accessed Oct. 3, 2014)

About the Author

Geetha Jayan, PhD, is a Senior Science Health Advisor at FDA’s Center for Devices and Radiological Health. Views/opinions presented in this article represent the author’s and not the FDA’s.

Industry, Regulators Share Insights and Look to the Future

The PDA/FDA Joint Regulatory Conference proved to be a valuable opportunity for learning and information exchange regarding the key issues facing our industry, the initiatives championed by the U.S. FDA, and solutions emerging from the ranks of PDA membership. From the opening remarks on Monday, the stage was set for attendees to gain insight into many topics, starting with a look at how rapid scientific advances are driving the need for new manufacturing capabilities and analytical models.

Stephen Ostroff was the first plenary speaker, addressing the direction of the agency as we stand on the cusp of innovations in personalized medicines and genomics. He also addressed the range of new biological, chemical and radiologic threats requiring industry/government and academia to collaborate. The Medical Countermeasures Initiative is a front line defense to not just terrorist threats, but also natural disasters such as the current Ebola outbreak. “Extraordinary challenges bring great responsibility,” he said, invoking J. Robert Oppenheimer and his memorable quote regarding “heroic days,” giving attendees a call to action to use the scientific approach to address the great challenges of our time.

The second plenary session covered “Analytics & Manufacturing of the Future,” with valuable perspectives from both Amgen and CDER. Next generation manufacturing and its role in preventing future drug shortages was discussed. Against a backdrop of increasing market and supply chain complexity, drug shortages have increased fourfold in the period of 2005–2011. Quality, capacity, and raw materials were cited as the key drivers. Regardless of cause, the resulting patient impact is unacceptable. Madhu Balachandran introduced the audience to concepts being used at Amgen to ensure supply interruptions are minimized, and described how, in concert with Next Gen Manufacturing techniques, variation can be reduced and six sigma performance achieved. Balachandran enlightened the group regarding the Amgen approach to ensure supply: linking the four pillars of prevention, technology, inventory, and diversification. In an interesting analogy, he discussed how the U.S. Nuclear Navy’s “Defense in Depth” program—which provides a systemic approach to deliver highly reliable operations in an incredibly risky field—might serve as a model to pharma.

Mansoor Khan shed light on the concerning number of Field Alert Reports (FARs) resulting from particulates, and their connectivity to drug shortages. Khan discussed the myriad reasons for these incidents, ranging from operator training to filter issues, impurity/degradation products, and API coming out of solution. He challenged the industry to consider the application of Process Analytical Technology (PAT) to improve product quality, and gave a lyophilization example relating to the use of in-process measures such as temperature to prevent later particulate formation.

In a session addressing the Cost of Poor Quality, attendees gained perspective from industry and regulators regarding the critical nexus between quality investments and business success. The cost of fixing quality issues continues to increase, and funds can be better invested in continuous improvement driven by risk assessment and scientific rigor. In the emerging paradigm of Quality Culture, compliance must follow from thorough product and process understanding…not vice versa. This becomes even more critical as breakthrough therapies will rely on advanced manufacturing initiatives. Strong leadership is critical to develop and maintain a true culture of quality. Manufacturing needs an equal seat at the table with the R&D and commercial organizations as pharmaceutical companies determine how to allocate spending—and there is opportunity as an industry to promote the “business case” behind proactive risk management and quality investment.

Besides the plenary sessions, there were a range of concurrent sessions to choose from. Quality by Design was a recurring theme in some of these sessions. Chris Stevenson, Sr. Manager, Quality innovation & Lifecycle Management, discussed the implementation of QbD on legacy products at Baxter, highlighting how the application of QbD to multisite products has allowed them to identify and benchmark optimization opportunities. Jeffrey Baker, PhD, Deputy Director, CDER, confirmed that while CDER is seeing increasing use of QbD in submissions, there are some differences. Good science abounds, but there are a range of approaches to translating that understanding to control strategies. He also debunked a few misconceptions, such as that there is no such thing as a “QbD” or “nonQbD” submission, and no such thing as too many or too few controls. QbD is not a program, brand, or deliverable; it is about understanding the significance of data—Baker likened it to comparing a pile of bricks (data) to a house (QbD).

The advent of continuous production was discussed by Gordon Muirhead, PhD, Vice President Oral Solid Dosage Forms, GlaxoSmithKline. Such processes are very amenable to QbD in comparison to batch processes. PAT provides the right metrics to reduce variability—enabling companies to measure more meaningful parameters than blending time, for example, and focusing instead on properties indicative of blend thoroughness. On the flip side of “manufacturing of the future,” the dilemma of aging facilities was covered. The reasons to update facilities are myriad: high process variability, improper or outdated analytics, equipment age and resulting issues obtaining spare parts, to name a few. Maik Jornitz, President, G-Con, discussed the important efforts of PDA’s Aging Facilities Task Force, which has subgroups dedicated to facilities, processes, and analytics and seeks volunteers. Ghada Haddad, Associate Director, Engineering, Merck, shared her experience and challenges in ”renovating and innovating” an existing facility, to upgrade equipment and processes (isolators and VHP) while increasing capacity.

Marla Phillips, PhD, Director, Xavier Health, Xavier University, brought unique insight to pharma/supplier relationships. A Xavier study revealed that contrary to popular belief, lack of reliability of incoming materials was not due to “poor supplier performance,” but was more attributable to issues caused by manufacturers themselves; Xavier continues their work with industry to develop and codify Good Supply Practices (GSPs).

Plenary sessions on the final day were kicked off with a compelling “Patient Perspective” session, in which Terry Sarisky shared the personal story of her mother’s fight against brain cancer, and the critical role that innovation and clinical research can play in saving and improving patient lives. Various FDA leaders then participated in panel discussions regarding Compliance and Center Initiatives. Following the reorganization of FDA, there are multiple agency priorities, ranging from Food and Drug Safety and Innovation Act (FDASIA) and Drug Quality and Security Act (DQSA) implementation, to quality initiatives and preparedness activities.

Overall, the event celebrated the advances of our industry, the important alliance between industry/regulatory/academia, and highlighted the fact that, despite the noble efforts we undertake, the increasing complexity of our challenges creates new risks, which require new approaches and a redoubled focus on quality.

About the Author

Erin O’Brien joined West in 2009. In her current position as Senior Director, Marketing, she leads West’s marketing efforts for the Pharmaceutical Packaging Systems Division in North America.