The first edition of this guide was published four years ago. The broader world has changed in many ways since then, as exemplified by the election of Donald Trump in the US, the Brexit vote in the UK, prosecutions of leading Brazilian officials, new governments throughout the world, strong, synchronised global growth, and extraordinary technological changes, including the increased role of artificial intelligence. Not surprisingly, regulations surrounding healthcare products have also changed, sometimes in small increments and sometimes in giant leaps. And the world has become increasingly digital. Reflecting this latter shift, the guide is now being offered exclusively in an electronic format.

While some patterns have been disrupted over the past two years, when the last edition was published, that is not the case for the adoption and utilization of healthcare products. Since the last edition was published, the importance of drugs, devices and biologics has continued to grow. The sales of these products have continued to expand.

Many different factors drive this trend. One factor is technology itself. There have been extraordinary advances in basic and applied sciences, leading to the development of new products. The deciphering of the human genome, followed by tremendous strides in understanding the basic underlying disease processes and genetic regulation, has helped pharmaceutical companies develop drugs that are targeted at specific disease-causing mechanisms, and led device companies to create more sophisticated and targeted diagnostic tools.

The technical achievements are highlighted by the first approvals of products that alter the human gene. This was the stuff of science fiction a few years ago, and now it is commercial reality. Researchers have learned to differentiate between different types of cancer based not on the site of the tumour, but on its underlying biology. The focus has increasingly shifted from where the cancer is found to its genetic make-up. In 2017, the US Food and Drug Administration (FDA) approved its first drug that was based on the cancer's genetic make-up rather than anatomical location of the tumour. That, in turn, has led to targeted therapies and the growth in diagnostic tools required to differentiate between these types of cancer. A whole range of disciplines that did not exist a few years ago (such as bioinformatics, metabolomics, epigenomics, and proteomics) are spurring the development of new therapies and diagnostics. Gene therapy is now a reality. Drug and device companies - or consortiums of companies - are racing to gather and sequence genetic information and use that data, in combination with medical records, to derive new insights for better, more specific therapies. These technological advances also enable consumers to play a greater role in managing their own healthcare, including access to genetic information and utilisation of a plethora of health-related apps.

Similarly, new technologies, new materials, greater computer power, more powerful algorithms, artificial intelligence, the rise of the cloud and smartphones, and a better understanding of human physiology have accelerated growth in the medical industry. New or improved non-invasive diagnostic devices have enhanced clinical diagnoses and improved patient management, which can in turn spur the use of pharmaceuticals. Further technical breakthroughs will occur as a result of the heightened research focus by governments, academia and industry on the functioning of our most complex organ: the brain. The results of those studies will almost surely lead to new therapies and diagnostics, as well as new regulatory paradigms to address these products, for example, what is the clinical endpoint and how to weigh benefit and risk.

Other factors have also contributed to the growth in new products. Life expectancies are increasing and global populations are aging, stimulating demand for drugs and devices. The middle class has grown dramatically in many developing nations. There is an increasing emphasis on access to healthcare in more countries, and that will stimulate global demand.

Global growth is promoted both by:

Products that can meet requirements for improving accessibility and affordability, or demonstrating significant cost-effectiveness, are particularly well positioned to partake in this growth.

Therefore, there are powerful forces that should lead to continued substantial growth in the research, development and introduction of healthcare products. There is a profound trend in favour of growth despite the existence of significant impediments, such as issues relating to cost, third party coverage and payment, regulatory uncertainty, product liability litigation, patent thickets, the increasing cost of product development, and no assurance of success, as illustrated by multiple failed, costly trials with drugs to treat Alzheimer's disease.

Another powerful force is globalisation. The healthcare market is an increasingly global market. More companies are looking to markets not just in their home country or region, but in numerous other markets. Sophisticated manufacturers are crafting strategies for multiple types of markets. Some companies try to incorporate plans for global marketing from the outset, while others take a more stepwise approach. Designing a costly clinical trial to satisfy only one country's regulatory regime can be a costly mistake, but idiosyncratic local regulations can impede conducting a study that satisfies everyone. The very concept of "home country" has changed, with companies redomiciling or opening key facilities in multiple countries. Companies are also looking at cross-border transactions, with the volume of mergers and acquisitions remaining quite healthy. Legislation and tax incentives can also influence where companies locate and how and where they spend their money. The new Medical Device Single Audit Program (MDSAP) exemplifies the breaking down of international borders, with one country's inspection helping to satisfy the regulatory requirements of other countries.

While it is easy to advocate a global strategy, executing such a strategy is tough. A company selling in the US cannot just replicate its experience in Europe and expect to succeed there, let alone in even more diverse markets, such as India and Brazil, or in smaller, less developed countries. The term "global market" is itself a misnomer; companies can sell throughout the world, but markets have very different characteristics. Partnering can help, but companies must choose partners with care, and relying on a partner without some understanding of local laws is a mistake. There are no model distribution or partnership templates that fit all countries perfectly, in part because of the difference in regulatory regimes. Global supply chains present their own sets of challenges. A hiccup with any supplier can create headaches everywhere; one variable is that suppliers must meet multiple regulatory standards.

One of the most important differences between markets is the applicable regulatory regime. Drugs, devices and biologics are not consumer products that can be freely sold. In many countries, a company cannot simply start selling a new cardiovascular drug or knee implant without first complying with some government regulatory requirements. These requirements can be extensive and complex, and costly to satisfy. In addition, the continued marketing of products must also comply with the relevant regulatory framework, including promotion, advertising and manufacturing standards. The need to tailor websites to meet the regulatory requirements at different countries underscores that marketing practices are not universal, and global harmonisation is extremely unlikely.

These regulatory regimes vary significantly from country to country. A manufacturer that assumes its regulatory experiences in one country will help guide its experiences elsewhere is very likely to stumble. Drawing false analogies between countries can be costly and dangerous. For example, one of the best developed and most comprehensive regulatory laws, the US Federal Food, Drug, and Cosmetic Act, which was enacted in 1938, has been amended many times since then. There have been several pieces of major legislation adopted since the last edition. These changes make the law even more complicated. Simplification is, unfortunately, rare.

The US statute applies both to drug and device manufacturers. Some of the provisions, such as the prohibitions on the introduction of "adulterated" or "misbranded" products, are identical for both drugs and devices. Based on their familiarity with US law, drug manufacturers will sometimes assume that they understand key facets of the device regulatory system (and vice versa). Usually, they are wrong. Even terms that are the same for drugs and devices (such as "good manufacturing practice" (GMP)) have different meanings in the two systems. While it may be reasonable to assume that the term GMP would have the same meaning for both drugs and devices, that assumption would be wrong. Although there are similarities between drug and device GMPs, these also differ in material ways.

The example above can be used throughout the world. Given that a US drug company cannot rely on its own drug GMP experience when evaluating a US device company's compliance with device GMP, it is considerably harder (and more imprudent) to apply local experience to an entirely different country, with different laws, rules, policies, cultures and norms. Even worse, those requirements are constantly changing. A company that relies on its understanding of the law from two years ago may be in for a nasty surprise. Strategies and tactics need to be continually updated as laws, regulations, and policies evolve.

Therefore, it is critical for companies, or individuals advising companies, to have information about the regulatory systems in various countries. However, this information is difficult to obtain. There is a need for one source that allows companies, lawyers, analysts and others interested parties to rapidly and conveniently obtain insights into the healthcare regulatory regimes in key markets around the world. This guide helps to fill that gap.

By compiling descriptions of the drug and device regulatory regimes for 26 different countries, this guide provides in a single resource key insights into how these products are regulated around the world. The countries represented in the guide account for a significant fraction of the global population and global expenditures on drugs, devices and healthcare products. Chapters cover developed countries that are both leading consumers of healthcare products and developers of such products, including the US, UK, Germany and Canada. Critical emerging markets are also covered, including India and Brazil, which represent both burgeoning markets and increasingly important products. In addition, other smaller but important markets are included, such as Mexico and South Korea.

The structure of the guide enables readers to obtain a rapid overview of the regulatory system for each country. The same format is followed in each chapter, addressing key elements of the regulatory regime for each country, such as the drug and device approval systems, and controls on marketing and post-marketing enforcement. The use of the same structure facilitates cross-country comparisons. This approach makes it easier to quickly discern key similarities and differences between countries with respect to a particular regulatory area, and to understand better the types of questions to ask when contemplating a new market. The guide has also been updated to cover an important recurring, vexing issue: how countries decide whether a product is a device or a drug.

Each of these chapters was written by individuals who regularly work with that country's regulatory system, which is an important strength. In theory, one could carefully "read" the laws of various countries and conclude that they now understand how a particular country regulates a specific area; but such an approach does not work. A global constant in healthcare regulation is that a company is doomed to fail if it believes it can understand what is really required just from reading laws and rules. It simply does not work that way. Laws are a starting point, but companies need to understand policies, guidance, informal customs, and layers of nuances.

Under a regulatory scheme, words can have very different meanings from their ordinary meaning. Persons who simply rely on their understanding of the ordinary and customary meaning of words used in the laws and regulations will be inevitably disappointed when trying to obtain approval for a product or dealing with government regulatory authorities. Understanding how healthcare products are regulated requires knowledge of "lore", not just law. Gaining insights into this "lore" can only come from experienced individuals who routinely advise companies on their regulatory system's details and foibles.

Another principal feature of healthcare regulation is the pace at which the regulatory landscape changes. For example, the US Congress has enacted several new major laws in the past two years, and the FDA is regularly issuing new regulations and adopting new policies that can profoundly affect healthcare manufacturers. For example, since the last edition of this guide was published:

These are just a smattering of the numerous regulatory changes in the past two years.

This guide is intended to provide a summary, not a comprehensive review of each regulatory framework. Many of the individual topics covered could be the subjects of books in their own right. Indeed, there are books just on US regulation of drug GMPs. There will be times when a comprehensive review of a particular topic is needed, and other resources or direct contact with experts will be required. However, this guide is a valuable resource as it provides current information on a wide variety of key markets in a standardised, easy-to-compare and digest format.

The healthcare industry is poised for continued growth. Participating in this growth, though, is not simple. Companies that wish to join in this global growth need to understand the regulatory framework of the countries in which they plan to sell. Such knowledge will help when developing products, conducting clinical studies, crafting intended use statements, positioning a product, complying with ongoing regulatory requirements, negotiating agreements, making strategic decisions, evaluating investment options, evaluating potential transactions, product marketing, and in a multitude of other ways. This updated, refreshed, and expanded guide should help companies, investors, analysts, researchers and others better understand this critical and evolving global regulatory landscape.

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