By: Robert M. Califf, M.D., Commissioner of Food and Drugs
India sometimes describes itself as the “pharmacy to the world” because it is a significant global supplier of affordable therapeutics, including many life-saving medicines for chronic conditions. For the U. S., where more than nine out of 10 prescriptions dispensed are generic drugs, India is a critical partner, responsible for a substantial portion of these drugs. I recently visited India with a central purpose in mind—to strengthen our collective efforts to advance the development and availability of medical products that both our countries and the rest of the world needs.
Fifteen years ago, the U.S. Food and Drug Administration recognized India’s strategic importance to the U.S.—and to the agency in fulfilling our mission—and opened one of the FDA’s first foreign offices in India. Since that time, the Indian medical products sector has continued to grow as has our reliance on medical products made in India. These were drivers for my decision to travel to India where I met with Government of India officials, pharmaceutical company CEOs, academics, clinical researchers and innovators.
Traveling to New Delhi and the Pharmaceutical Hub Hyderabad
While I had been to India many times before as a clinical cardiologist, academician and clinical trialist, this was my first visit to India as a representative of the U.S. Government. One of my key messages during my visit to the capital city of New Delhi and the pharmaceutical and technology hub Hyderabad was that India’s role in the medical product space represents both a unique opportunity and an important responsibility.
I heard about and visited firms that are doing a tremendous and reliable job. And although the Indian pharmaceutical sector is best known for its generic drug production today, the industry is also keenly interested in the development and manufacture of novel therapeutics, vaccines and digital health technologies.
For the moment, however, generic drugs are front and center, although the economics of the industry can be challenging these days. As I repeatedly heard in my meetings with India’s pharmaceutical leaders, there are many critical generic products where profit margins are thin or nonexistent, making it difficult to invest in technology and in people. And yet the U.S., and indeed the world, is relying on Indian pharmaceutical companies to make safe, effective, high-quality drugs, that can be trusted to have their intended effects and to remain consistently available. A significant part of the solution to our drug shortages in the U.S. is to create transparent quality systems that enable investment in firms that are reliable and quality producers.
Promoting Manufacturing Quality and Data Integrity in Support of Drug Applications
Going into my trip, I knew there had been global attention focused on recent serious instances of quality failures involving cough syrups manufactured in India that resulted in deaths among children, although none of these cases occurred in the U.S. And separate from these instances, I knew that our FDA investigators had identified issues in India demanding our attention relating both to quality of manufacturing systems and concerns with the conduct of clinical trials performed in support of drug applications. Throughout my time in India, I repeatedly spoke about the importance of prioritizing a culture of quality and practices that ensure the integrity of manufacturing and clinical data.
The FDA requires all manufacturers making products for the U.S., no matter where they are located, to abide by current good manufacturing practices, or CGMPs. CGMP requirements are intended to provide minimum standards for the sound design, monitoring, and maintenance of manufacturing facilities and processes. Beyond CGMP, manufacturers are encouraged to adopt a top-down, bottom-up culture of quality that allows for critical feedback from operator to manager on processes to ensure compliance as well as facilitate continuous improvement. Failing to maintain effective manufacturing quality management can result in supply disruptions and quality failures which lead to product shortages when manufacturing lines must be shut down. In fact, such failures have been a leading cause of recent shortages. We often see these quality issues when firms rely on feedback from periodic regulatory compliance inspections for appropriate corrective actions, rather than having a robust internal culture of quality that can comprehensively detect and respond to issues even in the absence of a regulatory inspection.
And before companies can turn to manufacturing certain drugs, they must get marketing approval, supported by clinical data. Not only is sound, ethical, clinical practice required by FDA regulations, it is our shared responsibility to research study participants and future beneficiaries of therapeutics that clinical studies be conducted in a way that ensures the integrity of the data and the protection of participants. This includes that study participants understand and consent to all risks, and that the clinical trials are designed and conducted appropriately so they result in actionable outcomes and protect the integrity of the scientific data generated. Best practices and ethical guidelines by industry, including contract research organizations, should build upon these requirements.
Strengthening and Harmonizing Regulatory Oversight for Pharmaceuticals
The Government of India has been engaged in efforts to strengthen their regulatory framework for pharmaceuticals, apply uniform enforcement and act on noncompliant manufacturers. In my meetings, I applauded these efforts, and encouraged further resources and strengthening of regulatory oversight to adequately support growing drug manufacturing capacity, increased engagement in international standards setting organizations, and continued partnership with the FDA and other regulators to establish an appropriate, clear, and consistent approach to quality. For example, the FDA works through its role as a Founding Member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) to develop and implement harmonized scientific and technical guidelines, and works as a Member of the Pharmaceutical Inspection Co-operation Scheme, an international organization dedicated to harmonizing inspection practices and related policies. I offered the FDA’s support to India to enable their participation in both. Such engagement is important for regulatory consistency and to enable regulators to work together efficiently and effectively. This is a key goal for the FDA with regard to India, as India has the greatest number of FDA-regulated drug manufacturing facilities after the U.S.
The discussions on my trip reflected a continued willingness and enthusiasm from the Government of India and industry alike to work collaboratively with the FDA to ensure robust quality management for safe and effective drugs. Collaborative work towards a high-quality, resilient and financially viable supply chain will be good for both countries and for the billions of other people around the world who would benefit from ample, proven generic drugs. Thus, ensuring a secure, resilient, and high-quality pharmaceutical supply chain is a high priority for the FDA, and India remains a key partner in this critical effort. Stay tuned for updates from the agency on this important topic.