“For the purposes of this discussion, ‘regulatory flexibility’ can be defined as a manufacturer having greater freedom to make postapproval changes to a drug-substance manufacturing process and controls, without waiting for prior approval from regulators, than the manufacturer may have had for similar changes approved in the past. ‘Manufacturing flexibility’ can be defined as a manufacturer being more capable of accurately predicting the consequences of changes to a drug substance manufacturing process and controls, based on the increased knowledge and understanding of the drug substance and its manufacturing process obtained from taking an enhanced approach to manufacturing process development.

FDA went on to say that, “manufacturing flexibility is valuable to manufacturers because it provides them with operational flexibility including the assurance that changes can be made without adversely affecting the quality of the material being produced. Regulatory flexibility is valuable to manufacturers because it allows changes to be made more quickly, which in most circumstances will help save money.

“In an ideal world, manufacturing flexibility and regulatory flexibility would go hand in hand. No manufacturer should be granted regulatory flexibility that exceeds the extent of the manufacturer’s manufacturing flexibility. Likewise, a manufacturer’s ability to make changes will be constrained unnecessarily if the extent of the manufacturer’s regulatory flexibility is smaller than the manufacturer’s manufacturing flexibility. Both types of disparities can exist. Manufacturers should not request a degree of regulatory flexibility that exceeds their manufacturing flexibility, and they should provide sufficient information in their submissions to justify the degree of regulatory flexibility being requested. Manufacturers should also consider pursuing the issue of regulatory flexibility internationally: As long as manufacturers receive different degrees of regulatory flexibility in different regions of the world, the full benefits of achieving manufacturing flexibility will be beyond their reach.”

This blog post is part of the February 2012 cover story of Pharmaceutical Technology on ICH Q11

In April 2011, the EMA’s Committee for Medicinal Products for Human Use recommended a label update for Biogen and Elan’s multiple sclerosis drug Tysabri (natalizumab). Late in January 2012, the FDA also approved the label change in the US.

Although touted as an effective treatment, Tysabri has also been associated with the risk of developing a serious and, often fatal, brain infection called progressive multifocal leukoencephalopathy (PML). The new label identifies that a certain antibody status (presence of anti-JCV antibodies) is a risk factor for developing PML. A test to detect these antibodies can identify at-risk patients, which is a development that marks a step towards personalised medicine — matching the right treatments with the right patients to maximize therapeutic effect.

In their press statement, Biogen and Elan added that Quest Diagnostics will be producing the STRATIFY JCV Antibody ELISA testing service in the US, which is the first blood test authorised by the FDA for the qualitative detection of JCV antibodies. When used with other clinical data from the patient, the test can help healthcare providers determine the risk for developing PML. Such testing has already been used in Europe since the label was updated last year.

Biogen and Elan have also identified two other PML risk factors: over two years of treatment with Tysabri, and previous treatment with medicines known to weaken the immune system.

Tysabri has had a rickety life. It was voluntarily withdrawn from the US market in 2005 because of concerns over PML, but relaunched in 2006 with a black box warning and a strict monitoring plan. In Europe, Tysabri was approved in 2006 but has been under close scrutiny by the EMA. The EMA has also kept a tight watch and finalised a review of the medicine in January 2010, concluding that the benefits of the medicine outweigh the risks.

As well as improving the safety of patients, the new label could also help to boost Tysabri sales. According to an article by Bloomberg, financial analysts have forecast that Tysabri could see its global sales grow to as much as $3 billion by 2016. Without the label change, the drug may only have seen sales of $1.5 to 2 billion.

The JCV diagnostic test is a good example of how pharma companies can improve their medicines. All drugs, unfortunately, have side effects but a lot can be gained by understanding how those effects occur—and in which patients. Biogen and Elan are not the only companies making efforts to personalise their medicines. As was well publicised last year, Sanofi’s Avastin had its breast cancer indication removed in the US. However, Sanofi is looking hard at the drug in order to evaluate a potential biomarker that could help identify which people might derive more substantial benefit from the drug. Interestingly, Avastin was in the headlines yesterday with Bloomberg running a news piece about how Avastin studies have pointed to potential benefits when used in early-stage breast cancer.

No doubt there is more to come in the world of biomarkers, diagnostics and personalized treatments.

The President noted that the economy had been weakened in part by outsourcing, and he used the terms manufacture, manufacturing, and manufacturers no less than 18 times in his speech.

But just how will this alleged opportunity to “bring manufacturing back” affect the pharma industry? Outsourcing is a huge part of the industry.

The global contract manufacturing market for pharma has been estimated at around $40 billion. Contract manufacturing of bulk and dosage form drugs alone may reach $86 billion worldwide by 2016, according to MarketResearch. Emerging nations such as India and China are largely reaping the benefits of this spend.

PharmTech’s most recent annual outsourcing survey, done in conjunction with PharmSource, showed that bio/pharmaceutical companies who are actively outsourcing to these two nations rose to 32% between 2010 and 2011. Those percentages are expected to keep rising.

We want to hear your thoughts on this issue. Is it feasible and/or desirable for pharma manufacturers based in the US to bring manufacturing back? Why or why not?

Addendum: Several industry reps  have commented on this topic via Pharm Tech’s LinkedIn Group. Check it out at LinkedIn.com and search for the Pharm Tech group.

They’ve also overlooked a lot of the positive aspects of the project. Deen will be offering diabetes-friendly recipes that do not comprise taste and appearing at diabetes cooking events across the US. The initiative is called Diabetes in a New Light.

But if you’re familiar with Deen’s cooking, you’ll be aware that a lot of her dishes are not exactly promotional of a healthy diet (examples include bacon cheeseburger meatloaf and southern fried chicken – you can take a look at the recipes on her website), which is where media criticism has been directed. Deen herself was also diagnosed with Type II diabetes three years ago, but only revealed this to the public this week, another aspect that has attracted criticism since she’s maintained her cooking style, despite the fact that diet is an important part of managing diabetes.

However, Deen makes a good point of saying in a press statement that “diabetes does not have to stop you from enjoying the things you love”.

At a time when obesity is rising, it’s important for us to be aware of healthy food, and chefs need to take some responsibility. Let’s be honest though, most of us don’t want to be healthy all the time, so we want to know how to make the best of our butter!

In their criticism, a lot of news sources have overlooked the contributions Deen is making to the diabetes battle. She claims to have made small dietary changes and to have worked more exercise into her day. Being a celebrity spokesperson for diabetes will also be a good influence – some sources have made snide comments about the connection between Deen’s weight, her recipes and diabetes, which will no doubt influence some people into avoiding unhealthy foods.

And with all the attention being focused on the responsibility of celebrities and chefs to promote healthy eating, Novo Nordisk and the pharmaceutical industry has gotten a bit lost. The pharma industry also has a responsibility to promote good health; indeed, this focus is becoming increasingly important in pharmaceutical business strategies as non-traditional companies, such as food and IT companies, muscle into the healthcare sector. Ernst and Young has a really good report about this trend available on their website.

Even though the diabetes campaign is partly to promote Novo Nordisk’s diabetes drug, Victoza, it’s also a step towards health education. According to one news report, many diabetes patients have trouble managing their diet. Havilah Clarke, senior manager, product communications at Novo Nordisk is quoted in the report as saying, “Based on what were hearing from some primary research we were doing, people living with diabetes thought that food was one of the most difficult challenges to address in their social lives. They thought they had to deprive themselves.”

Whatever Novo Nordisk’s intentions, it remains to be seen whether using Paula Deen will be a successful strategy given the amount of criticism the partnership has received. But there’s no such thing as bad publicity, right?

Despite the economic slowdown after 2006, the total number of dollars invested in US life sciences far outstripped the rest of the world. The US saw investments of $73.3 billion between 2007–2010, up from $38.7 between 2003–2006, an increase of $34.6 billion. In contrast, the next runner up, China, saw an increase in investments of $10.1 billion, to reach $29.8 billion in 2007–2010. Most other areas of the world witnessed much more modest increases, or declines in investment. For instance, Ireland, which still made the top 10, witnessed a decline in investments of $21.1 billion. This shows that despite the global economic slowdown and all the wailing and gnashing of teeth over the movement of facilities to Asia, the US is still receiving a huge amount of life-sciences investment. Those of us in the US should consider ourselves lucky.

On Jan. 4, 2012, the HealthCare Institute of New Jersey (HINJ) published a press release which evaluated the results of the 2011 biopharmaceutical and medical technology economic impact survey, a study (conducted by Deloitte) which concluded that the life-sciences industry continued to make up a key sector of New Jersey’s overall economy.

Although the responses of five fewer companies—24 in the 2010 survey compared to 19 the following year—generated less meaningful findings for the most recent survey, HINJ President and CEO Dean J. Paranicas pointed to the strong continued growth in New Jersey’s bio/pharmaceutical sector. “Although we had 20% fewer companies participating in this year’s survey, those that did supply data demonstrate that the life-sciences industry continues to be a major economic driver in New Jersey,” said Paranicas. “However, New Jersey continues to face stiff competition from around the world and within the US for our industry’s investment. If anything, this data reinforces the need for our leaders in Trenton and Washington to continue to pursue policies that create a more competitive and attractive business climate here, and we look forward to continuing to work with them to achieve this objective.”

The study also cited (factoring in the decrease in participation) a total economic impact from reporting HINJ member companies of $24.2 billion in calendar year 2010, as compared to $29.3 billion in calendar year 2009.

Paranicas went on to laud the recent actions taken by Governor [Chris] Christie and the state legislature to make New Jersey more competitive and attractive for life-sciences investment. They include an aggressive and competitive business recruitment and retention program, adopting the single sales factor as the basis for calculating New Jersey’s corporate business income tax, and enhancing the Business Employment Incentive Program (BEIP) to promote greater private sector collaboration with New Jersey’s universities and colleges.

However, every rose has its thorn. The study pointed out that the number of full-time employees decreased from 55,366 in 2009 to 51,619 in 2010, and capital spending dwindled from $1.5 billion to $0.9 billion during that same span of time. The Whitehouse Station, New Jersey-based Merck & Co. announced the elimination of approximately 13,000 jobs following the second quarter of 2011 as part of a cost-cutting initiative. This continues a workforce-reduction trend for Merck in recent years. According to a July 30, 2011, article from The Wall Street Journal, “[Merck] will have eliminated about 30% of the work force it had at the end of 2009, in the wake of its $41.1-billion acquisition of Schering-Plough.”

This reflects the long-growing trend among the industry’s financially dominant companies. Expansion in the form of mergers and acquisitions (M&A), without a focused emphasis on R&D to maintain and add to a workable pipeline, will enable access to only a finite amount of prosperity constructed on a delicate foundation of borrowed time. Paranicas pointed out that global R&D spending increased by $6.1 billion—one of the factors that has contributed to the continued success of New Jersey’s biopharmaceutical sector, despite some overexpansive M&A miscalculations, and the consequences as a result.

Last Thursday, FDA issued an interim final rule requiring manufacturers that are the only producer of certain drug products to report all manufacturing interruptions to the agency. Early notification will help FDA work with drug manufacturers and doctors to make sure that patients have access to life-supporting products. The interim rule was spurred by President Obama’s Oct. 31, 2011, executive order, which directed FDA to reduce and prevent drug shortages.

But the agency is not relying on just one tactic. In addition to the interim final rule, FDA is developing a tracking database to monitor drug shortages. The database will record the numbers of shortages, the reasons for shortages, and what steps FDA is taking to address and prevent them. The database is a high priority for the agency, which hopes to complete it in 2012.

Also, several observers have expressed concern that unscrupulous organizations could attempt to reap large profits from drug shortages. In response, FDA has begun analyzing reports about drug stockpiling and exorbitant pricing. The agency plans to provide the Department of Justice with information about these reported activities, and the Department will determine whether they are consistent with the law. This issue is on Congress’s radar, too: Senator Charles E. Schumer (D-NY) recently introduced a bill to make price gouging on scarce drugs a federal crime.

As any supply-chain professional knows, having one source of a crucial item is far from an ideal situation. If a drug is crucial but not profitable, we may not see new sources spring up to provide additional supply-chain security. But FDA’s initiatives promise to ease the threat of drug shortages and reduce patients’ suffering.

Yes, doing surveys is a pain.  So there’d better be a darn good reason.  Here’s a survey with 7 good reasons that I consider worth the effort.  The industry and participants benefit from the 9th Annual Report and Survey of Biopharmaceutical Manufacturing, and here’s why.
1)    The study questions are relevant and based on real-world experience. They are developed by a nonprofit global panel of industry experts—The Biotechnology Industry Council, which is a group of 270 biomanufacturers and key vendors that provide subject matter expertise, and submit, each year, a set of the most urgent questions and issues on strategic areas projected to become problematic in the coming year(s).
2)    Few comprehensive, quantitative analyses of this industry exist—The Annual Report includes responses from between 350 and 450 biomanufacturers annually. An additional 180-200 vendors also participate each year.  That’s a lot of detailed global production data!
3)    Trends over time present a compelling story—Measuring biopharma trends over years delivers far more than a simple snapshot of the industry’s current situation.  Measuring changes over time, and correlating those changes with real-world trends and experiences provides a compelling picture of the industry’s strengths, weaknesses, and future direction.
4)    Participants get trend data first, and for free—the study provides hundreds of respondents with free, extensive summaries of the current data, and aggregated responses from participants in over 30 countries.  Information is aggregated; no respondent information is provided. So data are more accurate, and valid.  (If more detailed information is needed, the annual reports are also available for sale).
5)    Participants see the most urgent issues—by reading the study questions, you’ll understand what is most important to industry thought-leaders.
6)    Contributing to industry benchmarking—perhaps most important, by participating in this study, you’re contributing to accurate benchmarking of the current issues affecting the industry today:
a.    Budget trends
b.    New technologies developed by suppliers
c.    New technologies demanded by end-users
d.    Hiring trends
e.    Outsourcing and offshoring effects on current jobs
f.    Productivity, and the impact of layoffs
g.    Impact of biosimilars on industry capacity
h.    Capacity bottlenecks associated with downstream production
i.    Implementation of quality management processes
j.    New technology adoption rates
7)    Contributing to global health—Participants not only receive a summary of the study, but also a $10 donation on their behalf goes to global health charities—up to $10,000.

With all these personal and societal benefits, few qualified biomanufacturers have reasons not to participate. So take the survey today.

Beginning this month, we are featuring monthly reader polls to gain your feedback on key advances in the pharmaceutical sciences and manufacturing. As the scientists and technical experts on the front lines, your input is a crucial component in understanding what the industry has achieved and where it will go in the future. We encourage you to provide your feedback in our first poll, which is examining advances in oral drug delivery and oral product forms. We will share the results with you at PharmTech.com, and along with further analysis, our July issue will take a retrospective and prospective look at drug substance and finished drug-product manufacturing, formulation development and drug delivery, outsourcing, and analytical testing.

We are interested in your feedback as well. In addition to our reader polls, we invite you to provide your input on what you think have been major achievements in drug substance and finished drug-product manufacturing, formulation development and drug delivery, outsourcing, and analytical testing. Lend your expertise and offer your input in the comment section to this blog or email your input to Patricia Van Arnum, executive editor, pvanarnum@advanstar.com. We look forward to hearing from you.

Drug companies, including Pfizer, are wooing insured consumers by offering copay coupons, which reduce the amount of money that the latter must spend for a branded drug. These coupons are intended to discourage a patient from switching to a generic therapy. To redeem the coupons, consumers often must submit personal information that allows the firms to promote products to individual patients.

The coupons may help consumers, but they oblige plan sponsors, such as employers or state governments, to pay high prices for branded drugs when generic alternatives are available. Drug companies can prevent plan sponsors from knowing when enrollees have redeemed the coupons by processing them through a “shadow claims system,” according to a statement from the Pharmaceutical Care Management Association. Copay coupons will increase costs for these sponsors by $32 billion over the next decade, according to research from Visante.

At a time when state governments and private companies are pinching pennies, it’s hard to believe that they will allow drug companies to use these tactics for very long. Arrangements such as Pfizer’s agreement to manufacture generic Lipitor for Watson, in exchange for a share of net sales, seem comparatively more benign. Deals like this don’t appear to constrain patients’ choice or force payors to spend more than necessary for a given drug. They might be the “least bad” option for drugmakers without new blockbusters on the horizon.