FROM A GLOBAL PERSPECTIVE
By John Skerritt, Ph.D.
September 20, 2022
Adjunct Professor John Skerritt is Deputy Secretary for Health Products Regulation in the Australian Government Department of Health and Ageing, which includes heading up the Therapeutic Goods Administration (TGA), the Australian body with broadly similar roles to the U.S. Food and Drug Administration. He is the 2016-2022 Vice Chair of the International Coalition of Medicines Regulatory Authorities, and Chair of the Scientific Advisory Council of the independent international Centre for Innovation in Regulatory Science. The TGA is also the 2022 chair of the International Medical Device Regulators Forum. He has extensive experience in medical, agricultural and environmental policy, regulation, research management, technology application and commercialization. He is the author of over 300 papers and 10 patents.
Staff from the FDA’s Office of Global Policy and Strategy spoke with the Deputy Secretary on September 6, in advance of his visit to FDA headquarters at White Oak, Maryland, to participate in a series of meetings with FDA leadership.
What are TGA’s responsibilities? How do TGA’s responsibilities compare to those of FDA?
The TGA’s responsibilities are similar to FDA but not identical. So, we regulate over-the-counter and prescription drugs, complementary medicines (which are called dietary supplements in the United States), medical devices, cell and tissue products and blood and the blood supply. We also regulate nicotine and vaping products, but we don't regulate smoked tobacco products and also regulate the advertising of all the products we regulate. We have some responsibilities over advertising that would be covered by the Federal Trade Commission in the United States – our advertising controls are fairly strict by global standards. We don't have the First Amendment to our Constitution. So, there are some specific things, for example, prescription drugs, but also a number of other products, which can't be advertised directly to consumers in Australia.
The TGA also has responsibilities for the scheduling of drugs and chemicals, a bit like the DEA [Drug Enforcement Agency] has in the United States. On the other hand, we don't regulate food (other than dietary supplements) or veterinary drugs.
We do all of this with a total of about 1,000 to 1,100 people and a budget of only $125 million U.S. dollars annually – nothing compared with the FDA's eye-watering budget.
And do you have user fees?
We have user fees. Again, they're of a different magnitude, but they do fully cover our costs of evaluation of drugs and devices. So, for example, a new drug application is about US$170,000 end to end for the application and evaluation fee.
That’s a bargain.
The other thing that's a bargain is at the personal level. Although I'm equivalent of the FDA Commissioner, it's only one of three jobs I have, so I'm also Deputy Secretary for the Department of Health and Aged Care – so a bit like the Deputy Secretary of HHS. And I also head the Office of Drug Control, which has some similar roles to the Drug Enforcement Agency. But I only get one salary, unfortunately!
Although the TGA is my main job, I can only devote about 60% of my time to it.
If you go to your website, you’ll find extensive information about Australia’s plans for international engagement. It is clear looking at these documents that you have both a regional and a global engagement strategy. Explain your vision.
Our international strategy has four objectives: to build a globally aligned regulatory framework while recognizing that countries should make sovereign regulatory decisions; to increase collaboration and indeed, where appropriate, work sharing for drug and device evaluation; to look at international networks for product safety and maintain supply chains, which have been especially important during COVID – given the need for the rapid exchange of information.
Finally, our fourth objective is strengthening regional regulatory capacity. Australia is an interesting part of the world, geographically. In addition to developed countries like Singapore and New Zealand, many of the countries in our region are still developing economies. And so, there's a real opportunity for us to help develop the regulatory and health system capacities of the countries of the Asia and the Pacific islands and we've actually been doing a lot of that in the region.
Talk about what work you’ve done in the region.
We have had three major programs to help strengthen regulatory authorities in our region; all are funded by our Foreign Ministry. Our initial program was for building regulatory capacity in Southeast Asia, especially for the review and safety monitoring of drugs for infectious diseases, such as malaria, TB and HIV/AIDS. What we found is that a lot of new drugs would come to market offering significant advances – for example in managing resistance to malaria or resistant TB. But the agencies in small countries such as Laos and Cambodia didn’t have the capacity to review these products, and so these new drugs couldn’t be rolled out. We've supported these countries by sharing our reviews, mentoring staff, and helping them build capacity. We've also encouraged more developed countries such as Thailand and Indonesia to become regional leaders.
Our second program was with the Pacific islands. These very small economies would often procure the lowest price drugs to treat high blood pressure or diabetes. But often these were drugs of questionable quality and not manufactured in accordance with good manufacturing practices, and their storage was often suboptimal. Our laboratory testing program showed that some of those drugs contained high levels of contaminants or breakdown products and were essentially not fit for purpose. So, what having the reassurance of testing does is that the countries can then procure quality drugs for important conditions such as hypertension, diabetes, even oncology.
When the COVID pandemic came along, countries in the region with relatively low regulatory capacity really struggled, including many countries in the Pacific, as well as larger countries such as Indonesia.
And so, in addition to supporting over 40 million vaccine donations across the region, Australia supported regulatory approvals for vaccines in Indonesia and Vietnam, helped build safety monitoring systems in a wide number of Pacific countries, and supported the local manufacturing of COVID vaccines in Thailand.
Finally, we are working with the Asian Development Bank, which is looking at investing not only in procurement, but also to support local manufacturing of vaccines in certain countries.
And related to this work, we currently have a disproportionate role in leading a lot of international forums. It's not a role that we've necessarily pushed to be, but maybe we have trouble saying no. So, we also currently chair the International Medical Device Regulators Forum, were Vice Chair for six years of the International Coalition of Medicines Regulatory Authorities, chair of the Centre for Innovation in Regulatory Sciences Advisory Board, and one of my senior staff is the current chair of the World Health Organization’s Committee on Substandard and Falsified Drugs.
There is also a personal connection for me. Although I'm trained in pharmacology and I've worked in neurology and immunology, I actually spent 10 years as a deputy administrator of one of Australia's government development assistance agencies.
You could argue while the work in the region is very important for us as a global good citizen, other areas of international collaboration are absolutely critical to us as well.
Let’s talk about some of that. You’ve also sought to align with a handful of other regulators – Canada, Singapore, Switzerland and the United Kingdom – to form the ACCESS Consortium. Why did you do that? Why these nations in particular?
Each member of the Consortium is a medium-sized regulator. But when combined, the Consortium serves a population of over 150 million people, making it quite a significant regulatory bloc of high-income countries. As regulators, we all have faced the same challenges. First, we are not as well-resourced as the FDA or the European Medicines Agency (EMA), and so it is a lot of work for us to independently review drug applications. And secondly, we were experiencing a submissions lag, companies were often bringing their drug applications to us months after the FDA and the EMA and then, as soon as applications are submitted, they were getting five separate lots of questions. So, we figured by working together, by providing a “joined-up” set of questions for sponsors we could actually reduce our workload and get those drugs to market early. We began this effort by attempting to better understand each other's systems, and Australia and Canada conducted a few pilots to see how review collaboration would work. We even posted staff in each other's facilities for extended periods. Since these efforts began, we've approved (or are currently reviewing) about 30 new molecular entities and eight generic drugs covering a wide range of therapeutic areas – and for some recent drugs with all five countries involved in the review. It's been a very profitable collaboration.
Is this effort what you call work sharing?
Yes, it's work sharing. The idea is that one regulator might look at one part of the drug application’s common technical dossier, another might look at the clinical part, a third might look at the quality part and another may look at toxicology. We essentially divide up the dossier and then share our reviews.
Each regulator can still make sovereign decisions. Sometimes the indications are slightly different, depending on the regulatory authority, because we may also go to our clinical advisory committees who may want to limit the indications to a certain age group or a certain comorbidity or whatever. In short, work sharing doesn't mean that you have to make identical regulatory decisions. And we can still dig into the dossier if there's a particular thing that we might be more worried about. I think it's fair to say for the first eight, nine or 10 drugs work, sharing added to our work burden rather than reduced our workload. But now we're seeing some real savings. The Centre for Innovation in Regulatory Science does a lot of benchmarking of regulatory performance and their numbers show that as a result of work sharing, how long we take to make a regulatory decision has been reduced, the submission lag has come down dramatically, our workload has decreased, and so has the workload of the drug sponsors because they get a consolidated set of questions from the ACCESS countries.
You also make use of assessments by comparable overseas regulators or cores. What is that?
Well, a number of countries globally have what's known as reliance pathways. So, for example, Singapore has a range of pathways - they might use an FDA review, and EMA review or a TGA review. and make what we call an abridged evaluation of the drug.
Australia has two comparable overseas regulatory pathways for drugs. If the indications are the same, and the FDA or the EMA have, for example, approved the drug within the last 12 months, we will do a very abridged review. We will still look at all the data. It's not an automatic decision, but we'll make a decision within 120 working days. If we’re looking at an older review by the FDA or the EMA, or there's some slight differences in either manufacturing site or maybe the indications, or something else, we'll assign it to the comparable overseas regulated B pathway for a decision within 175 working days. Even then, it provides a faster route to market and avoids the need to rework the work of other regulators.
Medical devices are a little bit different because there's still significant divergence in the regulatory systems for medical devices compared to drugs. But that doesn't mean we still can’t refer to an FDA PMA or 510(K) regulatory review to contribute to our own review. For many years Australia has heavily relied on European device reviews by notified bodies. A couple of years ago we expanded that approach to a wider range of countries. And what that does is, it reduces the amount of review work we have to do. It makes sense if someone in Canada has looked at exactly the same medical device and looked at the clinical information in detail, and we can access the clinical report and ask any questions in that report rather than having to start all over again as if Canada, for example, has never seen that device.
You are a strong proponent of global harmonization and convergence. How would you describe harmonization and what is it not?
Actually, I avoid the use of the word harmonization because of what it is not. Quite often people will see harmonization as the need for countries to have identical statutes, identical regulations, identical laws. And you know, the U.S. Code of Federal Regulations is a very different beast from the Australian Therapeutic Goods Act and Regulations, and we shouldn't be trying to tell each other how to write regulations. So, I tend to avoid the use of the word harmonization and prefer to talk about alignment and convergence. In fact, that’s something I’m going to talk about next week in a speech at the annual meeting of the International Medical Device Regulators Forum. I'm going to say, look, we're not here to harmonize our disparate medical device systems, I don't think we'll ever have the same regulatory system for medical devices in Europe as in the United States, and to spend a lot of effort trying to do that is frankly going to waste a lot of time. But that doesn't mean that we can't work together and have common approaches on such matters as software as a medical device.
Here’s another way to view alignment and convergence. All companies of a particular size look at their markets as global, not the United States only or Europe only, or Canada only, or whatever. If we recognize that we are working in a global market, then it's sensible for regulators to collaborate and align on such things as clinical standards. After all, it doesn't really help patient or physician confidence if one country has a lower standard for evidence requirements – dramatically lower – say, for a device or a drug than another. It only creates doubt in the minds of doctors and their patients.
I think that it's important for us to work together and where there are differences to understand them and explain them, because we're not here to remove all differences, but to at least understand them.
I’ve primarily been talking about the advantages of alignment and convergence and working together when it comes to premarket policies. Working together is very important for postmarket activities as well, when we start looking at safety and active pharmaceutical ingredient supply chains. What we found with COVID is that sometimes, even in a country the size of the United States, very rare safety signals didn’t emerge, but they did emerge in Europe, which collectively has about double the population in the United States, and they might never have emerged in a country like Australia, which has a smaller population than California.
What more can be done to enhance medical product safety globally?
I still think that we need to work out how we can better manage and identify safety signals on a closer to real-time basis. There are some excellent and well-established systems, especially through the WHO, but where spontaneous or so-called passive reporting of safety signals are documented and communicated, they have really been designed, I guess, for traditional drug rollout. With the vaccines and COVID and even with earlier examples where some signals arose with particular vaccines when they were used widely in populations, the question is whether the safety signals were detected fast enough.
I know that a lot of very valuable information is now coming from insurance claims in the United States – they're coming from registries and so forth. So, while I think that spontaneous reporting will always be at the center of regulatory safety systems there are other deep and valuable sources of real-world data. There is also a need for us to be faster and nimbler than we have been in the past. So, I do think that safety systems will have to evolve, and that's actually one of the workshop themes for the upcoming International Coalition of Medicines Regulatory Authorities meeting in November.
More and more FDA is being asked about what we are doing around supply chain resiliency and diversification. How are you handling this whole topic?
As a small country, and as a small market, we have to be very careful and realistic about information, so we have been striving to get more information about current and potential shortages so we can better manage them. In 2019, it became mandatory for drug companies to report both current and upcoming drug shortages and discontinuations. It had been voluntary before then, but with a greater number of reports available at an earlier stage as a result of mandatory reporting, we are able to implement strategies for conservation of a particular drug in shortage and implement other actions at an earlier stage.
We also stood up a team that looked at alternative sources of supply and developed ways to collect information on purchasing. Hospital systems tended to do their procurement and not talk to each other. We've been looking at significantly increasing the level of data sharing using protocols that don't breach commercial privacy or antitrust laws. We don't want cartel behavior between companies, but we do want a hospital system in Sydney to be able to talk to a hospital system in Melbourne about how much supply of a particular drug they have.
We've also put in place a number of strategies, even at the local level, to manage drug shortages. So, for example, if there's a regional shortage of a drug or even a national shortage of a drug, we can now allow a pharmacist to dispense two by 20 milligram tablets instead of one by 40 milligram tablets. Originally that change would have required a new prescription, even though it's exactly the same drug and the patient will take the same amount.
There are also some national initiatives underway where particular companies have bid for the government to support an increase in the manufacturing volume of certain generic drugs. Clearly, we can't use this approach to cover the whole range of generic drugs used in Australia.
In addition, with generics and other drugs, in Australia, private insurance doesn’t cover the cost of drugs; government subsidizes the drug. People pay a certain price for a drug, and the company receives a portion of that price. The government raised the price slightly for the very cheapest generic drugs and in return the drug companies soon will have to hold four or six months of stock of certain generic drugs in Australia.
While it might sound attractive to say that over time we can address supply chain issues by manufacturing every single drug in Australia in a country our size and even perhaps in a country the size of the United States, that's just not realistic.
What percentage of your drugs are currently imported?
It’s embarrassingly high. For prescription drugs, it's over 90%, maybe even 95%. And sadly, there has been a decrease in local prescription drug manufacturing in Australia. So, we are very vulnerable. In the first few months of COVID, airlines stopped flying because, of course, many drugs come in the cargo hold of passenger flights. And when we were going from hundreds of international flights, down to literally two or three international flights coming in daily, we had to work together with our government trade authorities to mount special flights to bring in drugs, COVID PCR tests and so forth.
We were very worried we would run out of medicines used for ventilated patients in ICU. That really prompted the idea that hospital systems had to share their drug inventory information. We were going to them saying, look, we just need to know what you've got in these six or seven critical drugs because you don't want a ventilated patient in the next city dying while you're sitting on enough for 200 ventilators. Now we've been using that momentum to collect this information more broadly for a broader list of critical drugs.
What is your relationship with the FDA now and what are your thoughts about that relationship going forward?
Well, I've always had a warm welcome on my visits to the FDA because as another aspect of Australia's international leadership, I'm the chair of a scientific advisory council for the Centre for Innovation in Regulatory Sciences, an organization in which the FDA also takes part. And except for the last couple of years during COVID, that brings me to Washington most years, and I've always been welcomed at the FDA to catch up with colleagues. And it’s not just about me – our staff at all levels, dozens and dozens of them, interact with FDA staff within the centers. We’ve found that close interactions with each of the center directors and senior staff have been tremendously valuable during COVID and will continue to be in the future.
We realize that the FDA, because of your size, your resources, your tremendous breadth and depth of staff, you really can be the global leader and you're often the first regulator to see particular products. But we’ve learned over time that you benefit from interactions with us and with other regulatory counterparts. Before I close, let me tell an anecdote to explain what I mean. Rick Pazdur, director of the FDA’s Oncology Center of Excellence, reached out to us and to Canada about participating in an international program he was developing called Project Orbis. He even came out to Australia with a team of colleagues as part of this effort. And I said to him when he arrived, you know, you’ve got so many oncology specialists, you’ve got so many advisory committees, why do you need Canada and Australia? And he said all decision-making is better when you can bounce ideas around and share reviews with peers who may not be super close to that review or idea to start with. While each country makes their own sovereign decisions, there are benefits that flow both ways from this information sharing.
And I've noticed that this way of thinking has continued during the COVID response. Both the CBER and CDER center directors have been active and regular participants in the ICMRA discussions on COVID therapeutics and vaccines. They’re not just demonstrating thought leadership – they have been putting ideas on the table to have them debated and they listened and learned from it.
It's really been, you know, the old idea of two heads being better than one, even if you are the biggest regulator on a planet.
And I think what I'm particularly encouraged by is that under the current administration with the strong support of Drs. [FDA Commissioner Robert M.] Califf and [Principal Deputy Commissioner Janet] Woodcock, we’re seeing a renewed international opening up of the FDA, after perhaps a period where domestic issues were higher on the agenda.
As regulators, we're always going to have to focus on the health and well-being of people who live in the countries we serve. We are officials of our own governments, but what I think that we've shown, whether it be through COVID or initiatives that started before COVID, is that working together we can achieve better outcomes than working separately.