Compliance Zen

Data Mining and FDA: What's Missing?

The FDA recently awarded Johns Hopkins University a three-year contract to develop advanced analytical strategies to mine the data residing within multiple FDA databases.  The goal is to find ways to allow drug and diagnostic firms access to anonymous premarket data (from submissions, failed clinical trials, etc.) related to safety and efficacy for specific patient subpopulations.  The project will, as FDA's Dr. Seyfert-Margolis notes, allow the agency to use "data mining with an eye towards sub-stratification of patients for efficacy and toxicity predictors."

Meta-analysis and data mining is actively encouraged in other product development fields outside of the life sciences. New product development specialists even have a term for such endeavors, "bookshelving." The intent is to flag previously gathered data from past products, experiments, failed innovations, consumer feedback, and so on, in order to take one of three possible actions:  skip portions of the development process, avoid dead-ends, or better target a product toward a specific set of consumers. In my book, Get to Market Now! Turn FDA Compliance into a Competitive Edge in the Era of Personalized Medicine, I walk readers through how to incorporate this type of meta-analysis and data mining in preclinical and clinical development, as well as include it in quality by design implementation and submissions.

A study published by the Tufts Center for the Study of Drug Development found that less than half of pharmaceutical and biotechnology firms today are pursing personalized medicine projects in their pipeline. Given the slow - admittedly steady - progress of the FDA to publish guidelines associated with various aspects of personalized medicine development and commercialization, it is a testament to the industry's belief in personalized medicine that so many projects are underway without firm FDA rules in place.

Unfortunately, FDA's contract with Johns Hopkins University does not also cover all the postmarket data in FDA's possession.  While some postmarket data is available already publicly, there is little doubt that the agency has access to a great deal more.  And to realize the greatest return on investment in data mining, bookshelving and personalized medicine development, as much data as possible needs to be included in any meta-analysis.  Forcing firms to seek out other individual postmarket databases will not only slow their meta-analysis, it will jeapordize the integrity of any results.  Afterall, what if the one postmarket database containing critically relevant information is ommitted from the data mining? How will firms know?

Until the FDA can make all of its premarket and postmarket personalized medicine-related data available, firms may need regulatory affairs data specialists, adept in finding, collating, synthesizing, analyzing data across multiple sources - but do such experts exist?

Building Compliance in India

This Spring I was invited to an International Informatics summit in Hyderabad, India with the aim of discussing global harmonization as a means to a competitive edge, especially when it comes to lab informatics. Hosted by the Waters corporation out of Germany, the two-day summit was an enlightening experience in which to participate and observe the sharing of knowledge about FDA-regulated data integrity inspections, informatics best practices, and the challenges faced by laboratories and manufacturers in an increasingly globalized marketplace.

Waters kindly distributed my latest book on turning FDA compliance to competitive edge to all the attendees as I gave the keynote address. My talk turned on how to take advantage of FDA’s increasing reliance on regulatory harmonization with the ICH, GHTF and PIC/S.

I noted how the FDA and the EMA have begun a pilot program to coordinate their reviews of quality-by-design submissions. Set to last until 2014, the pilot program is designed to ensure regulatory reviewers have calibrated their review criteria. If successful, companies can expect two things:

1. FDA will require quality by design-based submissions by 2015 or so; and
2. Companies will then need only compile one core submission (quality by design-based) with minor additions to meet both FDA and EMA requirements for marketing authorization for a new drug or biologic

Thus, given the time the required for a new drug to wend its way through the pipeline, now is the time to start collecting the data in the labs and in pilot plant manufacturing to enable such a harmonized submission.

To understand how important this simplified submission will be, a number of the speakers from local Indian pharmaceutical firms discussed their challenges when it came to informatics in their labs – both nonclinical setting and in manufacturing quality control.  Which data rules are important? If a test fails, some regulatory authorities allow a certain number of retests; others allow none. Which to abide by? Going by the most stringent would seem to be the most prudent, but it is also the most costly. And cost is a critical consideration given the revenues of most Indian pharma firms have fallen more than 30% since the worldwide economic struggles began in 2008. With no end in sight to economic malaise in the Western world, Indian pharmas are slowly turning their attention to the developing world and emerging economies of Latin America, Africa and the rest of Asia.

Informal discussions with Indian pharma CEOs and directors made me realize that this shift does not bode well for European and US Big Pharma dreams of entering and dominating these new regions. Indian pharma firms are much better positioned from a cost standpoint and an intuitive understanding of operating in up-and-coming economies than their Western counterparts. And given that most India pharmas are already manufacturing both brand name drugs and their low cost alternatives, the idea of Big Pharma – with its big costs, big overhead, big bureaucracies and 20^th century business practices – competing successfully in 21^st century emerging markets against the more lean, more hungry Indian pharmas must be met with some degree of skepticism.

To succeed, pharmaceutical firms in the US and Europe will need to take a page or two from India. The enthusiasm of Indian pharmaceutical executives, managers, and line workers is palpable. There is a tremendous desire in India to catch up with (and surpass) the West, and to stay at least one step ahead of the Chinese. This double pressure perception, from the top and the bottom, manifests itself in Indian pharmas aggressively scanning the horizon for every advantage they can grab – from new cutting-edge laboratory equipment to simplified, streamlined SOPs designed for ICH, GHTF and PIC/S compliance.

That said, Indian pharmas may – in some instances – be outrunning their compliance infrastructures. The May FDA Warning Letter to Aurobindo Pharma Limited found that environmental monitoring controls and finished product packaging and labeling operations were “inadequate.” While the FDA has few inspectors in India, that the agency can so readily find such inadequacies indicates that Indian pharmaceutical firms still have some ways to go to surpass their US and European counterparts.

From what I saw in Hyderabad, however, such a time is not far off. Indian pharmaceutical firms are taking advantage of India’s decades-old expertise in software development and innovation to re-apply quality lessons learned from IT into drug and biologics innovation.  And just as the Indian government provided tremendous subsidies and IT-based R&D tax benefits to Indian firms in the 1980s and 1990s, the Indian government has begun to offer similar such benefits to Indian firms and startups such as the Translational Health Science Technology Institute (THSTI). The THSTI was established in 2009 to speed the development of new drugs using a strategy taken directly from my book:  a collaborative drug development strategy, fostering collaborations among healthcare providers, hospitals, academic researchers and biotech companies. This 21^st century development collaboration is already gaining tremendous funding and support from healthcare foundations around the world, the most recent being from the Gates Foundation.

As Big Pharma struggles to shed layers of overhead and redundant sales forces while desperately casting about for ways to invigorate stale pipelines, Indian pharmaceutical firms are racing to succeed in the 21^st century, embracing quality by design, new laboratory equipment, cutting-edge software and lean compliance techniques. I look forward to watching their progress.