Tags Posts tagged with "regulation"


This is a guest post from the BiotechBlog Intern,  Fintan Burke. Fintan is a student at the School of Biotechnology at Dublin City University. Do you have a response to Fintan’s post? Respond in the comments section below.

As trade featuring Living Modified Organisms (LMOs) began to grow to an international scale during the late 20th century, the Convention on Biological Diversity determined that a framework should exist to ensure information was provided for LMO imports. A convention meeting at Cartagena, Columbia initiated negotiations for an international protocol in biosafety needs. For Africa, a continent increasingly reliant on LMOs to maintain a stable food supply, this protocol would signal the beginning of a convoluted path to establishing its own biosafety standards across dozens of countries.

When negotiations for the Cartagena Protocol stalled in early 1999, both the African Group in the Convention for Biological Diversity and the Organisation for African Unity (OAU, now the African Union) came together to collaborate on a model biosafety law for the African continent. In 2001 a draft was finalised by an OAU working group and presented to representatives of 28 African governments, who welcomed the model law as it addressed several factors the Cartagena protocol then lacked, such as an LMO approval process and liability legislation. By this time negotiations on the Cartagena protocol had resumed with the establishment of an intergovernmental committee (chaired by Ambassador Yang of Cameroon) to facilitate the preparations for the first meeting of the protocol parties.

The Cartagena Protocol finally came into force on September 2003. This, along with increased regional biosafety developments in Africa, prompted a revision of the African biosafety model law. The model law draft from 2001 was sent to major signatories of the Cartagena Protocol for advice on how to review it. This also had the effect of allowing countries that may have a future stake in African agriculture to have more of a say in African biotechnology standards. In August 2007, the Revised Model Law was created and in November presented to the African Ministerial Conference on Science and Technology. By this point, the Model Law had been instrumental in developing the biosafety acts of several African countries such as Ethiopia, Ghana and Mali.

2007 also heralded the arrival of Kenya’s National Biotechnology Development Policy and Biosafety Bill into its parliament for debate. Kenya, the very first country to sign the Cartagena Protocol, had its biosafety bill highly promoted by Dr Noah Wekesa, head of the newly created Ministry of Science and Technology. This bill was encouraged both by Cartagena Protocol directives and by the need to replace Kenya’s outdated Science and Technology Act of 1980. Though initial parliamentary debates were highly supportive of the bill, the 2007 General Election caused a political shake-up that resulted in a new coalition government and a reintroduction of the bill to parliament. This time, however, the bill was met with opposition from parliament members and anti-biotechnology lobbyists. The same report notes that one legislator, Silas Ruteere, claimed that the bill breached the Cartagena Protocol by not educating the public about LMOs. Other protests included negative impacts on trade and a declining quality of food should LMOs be introduced. These objections were largely ignored by parliament, which eventually passed the biosafety law in 2009.

Kenya’s challenge of slow legislative process and misinformation from lobbyists is not unique. The National Biotechnology and Biosafety Act of Uganda also faced a lengthy delay, despite both stakeholders and the Minister for Agriculture calling for a speedy approval to maintain Uganda’s agricultural and commercial viability. Despite the imperative placed by the Cartagena Protocol and the framework provided by the African Model Law, many African countries are still producing legislation that varies between each other. While both Kenya and Uganda were still able to initiate field trials for GM maize in 2010, stricter biosafety laws in Tanzania prevented researchers from doing the same. In a survey of African biotech stakeholders carried out by Obidimma Ezezika et al, such variety and protracted development of these biosafety laws was down to poor communication of the benefits of GM crops, a distrust of the private sector and a conflict with religious ethics.

It is peculiar that a continent so heavily involved in establishing the international biosafety standard should itself falter so close to home. The most recent report on the growth of biotech crops notes that the fastest growing adopters of biotech crops were developing countries; Mexico, Brazil, India and China. The absence of African countries is indicative of the slow development of its own policies.

Fortunately, progress towards harmonisation of biosafety law in Africa is taking place. A 2011 African Union report has recognised the inconsistency in African biosafety law and has emphasised the need to combine regional biosafety practices. Recently the African Model Law has also undergone revisions to reflect the finalised Cartagena Protocol and its amendments. For Africa a speedy adoption may be the only solution, as the lack of a legal biosafety framework is beginning to cost them in terms of foreign investment in research. For a continent infamous for its temperamental climate, the need for a stable LMO based crop for commerce and stability cannot be overstated.

About the author:

Fintan Burke is a student at the School of Biotechnology at Dublin City University. His main fields of interest include biomedical therapies and recombinant organisms.  Fintan may be contacted at fintan.burke2@mail.dcu.ie .

With the recent news of pharma’s frustration with more price controls around the world, John Avellanet, frequent Biotech Blog poster and author of Get to Market Now!, is grinning right now for having predicting a strengthening of such price controls back in 2009 and in 2010.  Here is a brief interview with John, covering price controls, comparative effectiveness, personalized medicine, and other industry trends.

BiotechBlog:  In your book, on p. 32, you noted an expectation for the role of NICE and other cost-efficiency-driven healthcare agencies to expand. What’s changed since then?

John Avellanet:  Last year the new government in the UK announced it was planning significant changes to the role of NICE and a shift to “value-based pricing.” Pharma firms were very excited about this change, but as I told my regulatory intelligence newsletter subscribers in October last year, “Value-based pricing will price drugs according to their clinical value to patients.” In other words, as I pointed out in Get to Market Now!, cost of a drug is being directly equated with efficacy and safety. Medicine approval and reimbursement simply has to be based on efficacy and safety. The greater the efficacy and safety of the drug, the greater the price.

BB:  So you see this trend increasing?

JA:  Without question. The US’s recent initiation of comparative effectiveness studies under the aegis of the Institutes of Medicine, and the pilot parallel review programs of FDA and CMS – these are just baby steps toward more value-based pricing. Let’s face it, you can’t have a situation where the latest product is only 5% better but comes at a 75% premium – not in this economy. Private insurers and prescription management firms in the US started a number of these comparative studies last year because if they don’t get healthcare costs under control, they’ll go out of business.

BB:  What driving this cost-containment push? The economy?

JA:  Well, a lot of factors are actually converging – the weak global economy is only speeding the problem to be right now rather than 2 or 3 years from now. This was always going to happen because you have many powerful trends coming together:  costly knowledge specialization, aging demographics, growing globalization, diversion of regulation and technology, and so on. I spend significant time looking at a lot of these trends in the book – the entire first half of Get to Market Now!

If you look at all these trends together, it becomes pretty clear that no matter how you slice it, healthcare costs simply have to be capped. Now, there’s lots of ways to do this, but that’s not the point of the book.

Instead, with Get to Market Now!, I tried to answer a more pressing question for pharma and biotech firms:  “How can we still bring new innovative medicines to market for less cost?”

BB:  A lot of companies out there are offering specific solutions they claim will speed time to market and reduce development costs. How does the book handle this?

JA:  I avoid all those specific one-offs claiming to be silver bullet solutions. If it were that easy, we wouldn’t have this challenge, would we?

I walk readers through what’s worked for other industries faced with similar challenges, why it’s worked, and how to apply these lessons in pharma today. And I offer a lot of examples of drug and biologics firms successfully applying these techniques. There’s over 113 different tactics in the book that work, so readers can pick and choose what will work best for their organization. I’ve also got discussions with FDA officials, case studies and so on.

BB:  So the book isn’t just about the dialogue, it’s about what has worked for other and what is working in pharma and biotech today?

JA:  Correct. And thankfully, a growing number of industry executives, venture capitalists, and industry publications have deemed Get to Market Now! a success. It’s certainly generated a lot of interest because of both the analysis of the trends we face today and all the various tactics the book lays out, from using voice of the customer in preclinical, to quality by design throughout development and the post-market, to taking advantage of Foucault’s panopticon in regulatory compliance. The key is to use the regulatory constraints to your advantage.

I always say, “Think of regulations and reimbursement rules as the boundaries of the field. Now within the boundaries of the field, you can play any game you want or any combination of games. But the regs are the lines you can’t cross. So within the boundaries of the field, play to your strengths and everyone will cheer.”

BB:  Do you see these tactics also applicable to personalized medicine?

JA:  Yes, and perhaps even more so.  Remember, with a one-size-fits-all drug, you’ve got a huge percentage of the world’s population as potential customers. With personalized medicine, your potential customer base shrinks dramatically. If you can’t streamline development and put into play as many of the tactics in the book today when you’ve at least got the revenue base from a one-size-fits-all drug portfolio, how are you going to put them into play when you’re revenue has shrunk by 80%?

That’s the worry of a lot of the executives that bring me in to talk them through how to better apply these tactics to their companies. We know the tactics work – all the historical data from other industries proves it. So how can we start tailoring and applying them today, right now, before it’s too late?

For more on Get to Market Now! Turn FDA Compliance into a Competitive Edge in the Era of Personalized Medicine, visit the book’s dedicated resource site for readers, www.Get2MarketNow.com. Mr. Avellanet has made the first chapter free for download, plus a number of free mini-tutorials on some of the tactics from the book. The book is available through Amazon.com, Barnes & Noble, and the publisher, Logos Press.

Biotechnology Industry Organization CEO Jim Greenwood appeared on CNBC’s SquawkBox defending the case for data exclusivity protection for novel biologic drugs. The video appears below. Interestingly, he used the Aspirin vs. Epogen comparison from my book, Building Biotechnology, when he was explaining the difference between small molecule and biologic drugs to members of congress.

Guest content from John Avellanet, managing director and principal of Cerulean Associates:

Solving the FDA Crisis

John Avellanet

By John Avellanet, Managing Director and Principal of Cerulean Associates LLC

News of the latest crisis under the FDA’s watch – salmonella contamination and the peanut plant in Georgia – has all the usual suspects calling for increased inspections and hiring more inspectors. It won’t work. With all the money from the US bailout, the FDA could permanently station inspectors at every single biotechnology building, food processing plant, pharmaceutical site, and medical device factory in the US. And we would still have the problems we have today…only at an $800 billion price tag.

To solve the underlying issues we need an approach that will cost less, will strengthen our safety (especially as we enter the era of personalized medicines), and yet will still allow innovation and a level competitive playing field. This strategy will also need foresight – not only to expect that events will occur in the future that will challenge this solution – but to assume that without satisfying the public outcry when something does go wrong, the strategy will not last, and we will again be revisiting the “solution” when the next crisis du jour occurs. Put simply, we need a solution that can be applied with such tenor that it will “leave the people at once satisfied and stupefied” (Machiavelli, The Prince); we need stricter, harsher penalties.

The False Premise of More Inspections

As anyone with real-world experience in quality systems, information technology security, records management, or corporate espionage knows, you can have the best written rules in place, everyone trained, and auditors and inspectors in place, active, and auditing away, recording and documenting each transgression. So what? If the penalties are just a slap on the wrist – or in some places I’ve seen, a friendly chat – the transgressions will continue.

Malcontents and people who are ethically-challenged are always to be found. When I give talks and workshops on corporate espionage or quality systems compliance, I always review the four key reasons people do not follow rules: money, ego, ideology, or coercion. How does stationing an inspector at every building stop these motivators?

The reality is simple: for some people, just having the risk of getting caught is not enough. For these individuals, the risk of getting caught needs to be combined with the penalties for being caught, and together this must outweigh any perceived benefits to not abiding by the rules. And it is for these people that rules, regulations, policies and punishments are designed.

So if hiring more inspectors and increasing the frequency of inspections will not work, what will?

An Example that Works

All of us know the incredible annoyance of the telephone ring at dinner time as the telemarketers begin their evening onslaught. Thankfully, my children are growing up in a world where this does not occur. Is it because the telemarketing companies suddenly discovered that kindness and consideration preclude them from calling during family time?

Or is it to do with the National Do No Call registry? Think about it. By itself, the registry is just a big list. Again, so what? Just because you and I can put our names on a national Do Not Call registry does not really keep the telemarketing calls away, does it? Instead, the power of the registry has to do with the coupling of strict, harsh penalties associated with violating the rules.

And the penalties are simple and severe: $11,000 (USD) per sales call.

Ultimately, this is why the Do Not Call registry works – its teeth are both satisfactory and stupefying. It is satisfactory that people who knowingly violate the law have to pay so much. It provides us, as the consumers, the impetus to gleefully file complaint paperwork. And the penalty is stupefying. Would you like to pay $11,000 out of your pocket for a misplaced call? Or would that make you do everything within reason to avoid the misplaced call (and its associated penalty)?

So why is it that we’re willing to take this approach to stop a few phone calls every evening, but for products that enable us to actually live – food and medicine – we only suggest increasing the number of monitors?

The Way Forward

The FDAAA of 2007 took tentative, baby steps in the right direction. As attendees of my January teleconference, Bulletproof Yourself Against FDA Enforcement in 2009 (http://www.ceruleanllc.com/seminars), are quite well aware, the use of civil monetary penalties was expanded beyond just device makers, and the agency was given several powers of enforcement that it had long argued in the courts it required. Under the possible roadmap of the Do Not Call registry, however, the FDA is still sorely lacking in its ability to levy penalties against those executives and companies who do not produce safe products. And as we move from the one-size-fits-all medicines of the 20th century into drugs tailored specifically to your or my genetic makeup, product safety needs to be much, much higher on our priority list than stopping a telemarketing call or two.

There are three steps we can take to ensure a more consistent degree of safety in the products we get from companies under FDA jurisdiction:

1. Increased Penalties. Penalties for violation of FDA regulations and laws need to rise to at least the level of Do No Call penalties. Today, a firm receiving a Form 483 inspectional observation has no real penalty; only if the observed deficiency is “grossly deficient” will the company even risk being temporarily shut down until the deficiency is resolved. How effective would the Do Not Call registry be if instead of the $11,000 fine per call, it was only a “gross deficiency” of not following the registry that might cause the telemarketing firm to be temporarily stopped from making calls until they agreed to not call anyone on the registry? Instead, under a stricter approach modeled on the eminently functional Do No Call registry, a firm receiving a Form 483 inspectional observation might be assessed an $11,000 fine per observation; this would not be immediately due – rather, the firm could have the same process that exists today to head off a warning letter (e.g., fix the problem within a defined time period). If the firm does not fix the observation to the agency’s satisfaction (no different than today), then the warning letter is issued along with a penalty statement explaining that for each item listed on the letter, the firm is required to pay $11,000 per day until resolved. The firm would also be required to hire an independent third-party to inspect and certify that the violations were resolved.

2. Increased Incentives. At minimum, incentives for whistleblowers, consumers, healthcare providers, and even other non-FDA inspectors (customs agents, state food inspectors, etc.) need to be increased to encourage the filing of substantiated claims. For instance, we could look at the financial incentives from Sarbanes-Oxley as a possible model; a whistleblower of an FDA-regulated company whose allegations were proven correct could receive 10-30% of the levied fines as a thank-you for helping to protect the public.

Lest the incentives are all seemingly against firms, positive reinforcement should also be granted. At a minimum, rather than just publishing the list of firms who’ve demonstrated poor controls in its weekly enforcement reports, the agency can note firms who successfully passed inspections or otherwise adequately resolved previous issues. As shareholders increasingly agitate against executives who delay product launch because of FDA noncompliance, this type of public commendation can be a positive tool for executives seeking increased funding or new product approvals.

3. Strengthened Early Inspection Triggers. Today, the agency inspects firms for one of three main reasons: routine (also known as “surveillance”), for cause (such as a whistleblower complaint or adverse event or recall), and pre-approval. Pre-approvals are generally undertaken when a company files an application to sell a product in interstate commerce (pharmaceutical companies, for instance, file an NDA or ANDA). For medicines – including medical devices – a pre-approval inspection should also regularly occur when a company wants to start clinical trials. For foodstuffs, state agencies are the main inspectors, with the FDA chronically understaffed in this area. While state agencies should continue to play their role, the rules could be strengthened to force first-time manufacturers and processors to undergo a joint state-FDA inspection prior to allowing the product on the marketplace.

There are other items as well that would strengthen the incentives for making safe, efficacious and quality products while lowering taxpayer costs. Congress can encourage the FDA to expand the current joint inspection pilot programs with authorities in Canada, the EU and Australia to cover all medicinal products and foodstuffs. The agency can be more accepting of third-party and ISO-based inspections to stand in for nominal risk products (such as most Class I devices and foodstuffs).

Final Thoughts

Under this strategy, the FDA would need to publish a clearly defined baseline of inspectional criteria that will trigger the stricter penalties (much as the Federal Trade Commission publishes the clear list of criteria that will trigger the Do Not Call fines). Such a baseline would need to spell out that for the vast majority of – if not all – companies, inspectional observations such as “insufficient conveyor belt clearance” would not initiate a penalty unless other thresholds were also triggered; on the other hand, executives who decide to repeatedly test their product for the presence of contamination until they hit upon the “right” test and then pronounce their product “safe”, could be assured of painful consequences that would stupefy them and satisfy the public. The simpler and clearer the rules, and the stricter and swifter the penalties, the greater the adherence.

No regulatory schema or enforcement program is perfect; someone who values money, ego, ideology or coercion enough will eventually break the rules. But just as under the Do Not Call registry, this rule-breakage is extremely rare, so too should be the rule-breakage of FDA-supervised products. The question we face is ultimately one that asks us to choose between priorities: are good medicines and safe food more or less important than skipping a few telemarketing calls this evening?

Are you ready?

About the Author

John Avellanet is the founder of the regulatory intelligence and lean compliance program for executives and business owners, SmarterCompliance™. He is the author of more than 30 articles on lean compliance and quality systems, a contributing author to the book Best Practices in Biotechnology Business Development (Logos Press), the publisher of the SmarterCompliance™ newsletter, and a frequent speaker with FDA officials.

He can be directly reached through his independent advisory firm, Cerulean Associates LLC, on the web at http://www.ceruleanllc.com.

After months of effort, I’m pleased to announce the launch of Biotech U, a biotechnology education resource featuring web-based lessons on biotechnology business, law, IP, politics, regulations, and science.

Biotech U is based on Building Biotechnology, the leading text used in business-of-biotechnology courses. The online-learning structure is designed to meet the needs of busy professionals who seek a robust educational resource but lack the time to attend traditional classes. Feel free to try the sample course, an Introduction to Biotechnology, and I hope you enjoy this new resource.

A lot of people have been asking my opinion on when a concise generic biologic regulatory pathway will emerge in the United States, and I give them all the same answer: Later.

In my opinion complex regulatory schemes are not areas in which the United States can effectively lead. Why not? Because the size of the market makes tracking problems difficult, and implementing regulatory change can be very slow.

As I’ve described before, regulating generic biologics is no easy feat. A good regulatory scheme must address safety issues while enabling productive competition. Failure to accomplish either objective could potentially set the field back by years (consider the field of gene therapy which, despite some early signs of progress, is haunted by the deaths of study subjects).

The United States is the world’s largest pharmaceutical market, and accomplishing regulatory change can be slow. It is not an effective place to experiment with or refine generic biologic approval schemes. That is best left to smaller and more agile countries. Smaller countries often seek opportunities to serve as testbeds for emerging opportunities like alternative fuels, patient tracking, personalized medicine, etc. and will likely be the first places where comprehensive generic biologic regulations emerge (likely supported by consultants and regulators from the U.S. and EU).

The challenge to driving this innovation in smaller countries, however, is that they often lack the very resources necessary to test policy or technology innovations. This is where large nations, the EU, or agencies and organizations such as the WHO, ADB, IMF, etc could be directing their resources to simultaneously help development in smaller nations while supporting innovations offering global benefits, ultimately serving their own interests

The following appeal for generic biologic legislation was sent in from Insmed via youtube.

I’ve posted previously on the challenges of developing a framework for generic biologic approvals and questioned how much we can really expect to save. In the editorial for the upcoming issue of the Journal of Commercial Biotechnology, I argue that the United States is unlikely to lead in generic biologic regulation.

Got any ideas to overcome the challenges? I’d love to post them here or at the Journal of Commercial Biotechnology.