The report defines the biomedical sector as consisting of basic research, biopharmaceuticals, diagnostics, medical technology, research tools, laboratory services, and wholesale trade companies. When broken down by area, the employment news is not uniformly bad. Most of the job losses were from academia and from the device industry, and were partially offset by gains in the biopharmaceutical sector. CEOs within the industry were surveyed as to the reasons for reducing their company’s operations within the state. The top three reasons given were cost cutting, the overall business climate, and expanding new operations outside of California. Most CEOs were optimistic about the future, the majority indicating that they expected to either hold steady or increase operations inside and outside of California.

The investment climate has been affected by the economic slowdown, which in turn, affects the operations of companies in California. According to the report, more than 74% of respondents said that their company had delayed a research or development project in the past year, up from 69% in 2010. The overriding reason, at just over 40% of respondents, was cited as “funding not available.” In an accompanying press release, Tracy Lefteroff, national life sciences partner at PwC US offers this analysis. He says, “The life cycle of biomedical startup companies has changed as challenges to raising capital have increased. Whereas their greatest challenge in years past was in validating the science, these companies now need to validate getting funding by lowering costs and improving returns. The strength of California’s life sciences industry remains closely tied to the level of confidence that the investment community has in the industry’s ability to develop innovative products while effectively managing the challenges associated with clinical and regulatory risk.”

In terms of background, the BPCI Act was passed in March 2010 as part of Affordable Care Act, and it creates an abbreviated licensure pathway for biological products shown to be biosimilar or interchangeable with an FDA-licensed reference product (section 351k of Public Health Service Act). FDA is eager to have an informational discussion on this topic because with the new pathway program, the agency is “essentially launching an entirely new regulatory paradigm” and public needs to understand this, said Sherman.

The BPCI Act adds “protein” to the definition of a biological product which currently includes terms such as a virus, toxin, and blood. Historically, proteins have been approved as drugs under the FD&C Act (505) and under the PHS Act (351). Proteins (except for any chemically synthesized polypeptide) will be regulated going forward under PHS.

FDA can rely on some existing information about the reference product when considering a proposed bisimilar product. Specifically, “biosimilar” means the product has the same mechanism of action as the reference product; the condition of use in proposed labeling has been previously approved for reference product; and has the same route of administration, dosage form, and strength as reference product.

The agency has to decide whether the biosimilar product is highly similar to the reference product and ensure that there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency. A doctor can provide product A or B, for example, and expect the same result. The doctor cannot go back and forth between Product A and B, however (see below), noted Sherman.

The BPCI Act requires FDA to look at three buckets of information for the 351(k) pathway: analytical studies to show that the biosimilar is highly similar to the reference product; animal studies (including toxicity, and as needed); and clinical study(ies) to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed (including, among others, pharmacokinetics and immunogenicity).

A common question: biosimilars are not identical to the reference product but are close—how close? As Sherman explained it, each study adds a piece of information to understand what the biosimilar product is and shows what more is needed to fully understand it. The method is similar to a fingerprint like approach to closely identify the product. There is no one size fits all assessment. Another approach FDA may take is to use the totality of evidence in assessing the biosimilar. Europe has a similar way of evaluating biosimilars. To provide the best advice on required animal and human studies to the biosimilar applicant, FDA should have competed a thorough review of data from structural and functional analyses.

Interchangeability. This term means that the biosimilar product produces the same clinical result as the reference product in any given patient, AND for a product administered more than once, the safety and reduced efficacy risks of alternating or switching are not greater with repeated use of reference product without alternating or switching. An interchangeable biosimilar product may be substituted for reference product without authorization of a healthcare provider. NOTE: Biosimilarity is a prerequisite for interchangeability.

Discussions happening at FDA: The agency is thinking about ways to consider non-US licensed comparator products; the definition of protein (including chemically synthesized polypeptides); standards for interchangeability; naming and tracking standards for biosimilars and interchangeable products; exclusivity issues; and pediatric assessment requirements.

FDA will also be thinking about product class under the Act’s transition provisions. By 2020, every biological product will need to be approved under 351 of the PHS Act versus the FD&C Act.

To date, there have been 35 Pre-IND meeting requests for proposed biosimilars to 11 reference products. 21 PRE IND sponsor meetings held, and 9 INDs received

As for the FDA guidance on biosimilars…. Sherman says it’s still in final stages. No details on timeline specifics.

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.

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.

For Andrew Witty, the CEO of British pharma giant GlaxoSmithKline, the year is definitely off to a good start after he was knighted for services to the UK economy and pharmaceutical industry. Sir Andrew as he will now be known received the royal recognition in the UK’s 2012 New Year’s Honours List. Almost 1000 people received awards of varying kinds. 

This year, science and healthcare were well represented with other recipients of knighthoods including, among others, two physics professors, Professor Andre Konstantin Geim and Professor Konstantin Novoselov from the University of Manchester, Professor Stephen Robert Bloom from Imperial College London for services to medical science, and Dr Venkatraman Ramakrishnan from the Medical Research Council’s Laboratory of Molecular Biology for services to molecular biology. Julie Moore, the chief executive of the University hospitals Birmingham NHS foundation was also made a dame. Varying awards were also given out to other researchers and other pahrmaceutical industry particiants, including Richard Barker, the former director general of the Association of the British Pharmaceutical Industry (ABPI). There’s a full list available in The Telegraph. 

If you’re not familiar with the UK’s honours list, it’s a way of recognising merit, gallantry and service to the country. The lists are published twice a year at New Year and on the Queen’s official birthday in mid-June. The lists always comprises a number of film and sports celebrities, but it also reflects a range of skills and talents from across the UK.

The awards are also generally subject to a large amount of cynicism. For instance, The In Vivo Blog says, “Cynics may be suspicious of the timing of this flurry of biopharma-focused decorations. They came only a couple of weeks after the UK government outlined its new Life Sciences Strategy, in which much hope was placed on the sector helping to pull the UK economy out of the doldrums.”

I’ve also read some very cynical pieces that talk about the involvement of the British government in the honours process and the fact that Witty serves on an economic committee for the UK’s Prime Minister David Cameron.

However, most of the negative attention on the honour’s list this year has focused on other award recipients, such as Paul Ruddock who received a knighthood for services to the arts for his work as chairman of the Victoria and Albert museum. Ruddock’s hedge fund management company Landsdowne Associates made around £100 million after betting on the collapse of the bank Northern Rock. News reports have also pointed out that Ruddock has donated nearly £500,000 to the Conservative party. Some scathing has also been directed at the knighting of Paul Bazalgette, a TV executive who brought Big Brother to the UK. 

As a blog on our sister site Pharmaceutical executive points out, Sir Andrew could be seen as a bit of a knight in shining armour compared with other names on the list! GSK has pledged loyalty to the UK economy and has also sought to help developing economies by improving access to medicines. He’s also looking at some innovative ways to improve the company’s R&D by partnering with the McLaren Group. The knighthood will certainly be a good thing for GSK’s reputation, which has taken a bit of battering in the last year. In 2011, the company had to pay £1.6 billion to settle litigation cases concerning Avandia, which has been banned in Europe, while in the US the company has agreed to pay $3 billion to settle investigations into the way the company marketed certain products.

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The British Medical Journal (BMJ) took on this topic by publishing several articles that demonstrate how haphazard and incomplete the public disclosure of clinical trial data is. The FDA Amendments Act of 2007 made publication of a results summary on ClinicalTrials.gov within 12 months of trial completion mandatory for all eligible trials in the US initiated or ongoing as of September 2007. In a paper published in the January issue of BMJ, Prayle and colleagues  looked at studies completed between Jan 1, 2009 and Dec. 31, 2009, and found that only 22% had been reported on ClinicalTrials.gov by January of 2011. A second article by Ross and colleagues looked at NIH-funded trials, and found that of 635 trials completed by December 2008, only 46% had been published in a peer-reviewed journal 30 months later.

The omission of data can affect how the remaining data are interpreted. Conclusions about a particular drug’s efficacy are sometimes based on meta-analyses, where data from several independent studies are integrated to get a better idea of treatment effects. A study by Hart and colleagues reanalyzed 41 meta-analyses of efficacy incorporating unpublished data from FDA, and found the outcome to be the same in only 3 cases.

In an accompanying editorial, Richard Lehman, senior research fellow in the department of primary care at the University of Oxford and Elizabeth Loder, clinical epidemiology editor at BMJ underscore the seriousness of these lapses. “We are not dealing here with trial design, hidden bias, or problems of data analysis—we are talking simply about the absence of the data,” they write. “And this is no academic matter, because missing data about harm in trials can harm patients, and incomplete data about benefit can lead to futile costs to health systems. Moreover, researchers or others who deliberately conceal trial results have breached their ethical duty to trial participants.”

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NIH Establishes National Center for Advancing Translational Science

The draft performance goals outline timelines for review of applications, timelines for review of proprietary names, and procedures for resolving disputes. There is a section detailing the procedure a sponsor should follow to get specific questions answered about protocol design, or about scientific or regulatory questions pertaining to their submission, and a timeline for the agency’s response. In addition, there is an explanation of the types of meetings the sponsor should schedule with FDA, the information required by FDA before scheduling the meeting, and the timeline or conditions during the submission process that would require scheduling each type of meeting.

The detailed definition of each meeting type in the draft reminds us that FDA does not envision a “one size fits all” approach to biosimilars approvals. There’s a meeting for every contingency, and it appears that they anticipate a high degree of interaction between sponsors and government to shepherd molecules through the approval process.

See related articles:

FDA and Manufacturers Ponder Biosimilars Pathway – Pharmaceutical Technology

The report, commissioned by PCMA and prepared by Visante, analyzed the consequences of coupon use.  For the consumer, consequences are benign—branded drugs at lower cost.  However, according to the report, lower cost to the consumer comes at the expense of payers, who must cover more expensive drugs.  The report also claims that costs incurred by the drug companies by offering rebates are simply rolled into the cost of the drug, and passed back to consumers and payers. The report notes that the use of rebate coupons has risen by 260% in two years, and estimates extra costs associated with coupon use to reach $32 billion over the next 10 years.

The use of rebate coupons is barred in Medicare and Medicaid programs, where the government is the payer, according to the report. Alone among US states, Massachusetts, which has a mandatory health insurance law, bans the use of coupons.
This is yet another instance in which drug pricing does not adhere to the rules applied to consumer products. Cereal manufacturers have been using coupons for decades to retain market share and encourage brand loyalty. The difference here is that the cost of a drug is shared between the insurer and the consumer, with the insurer often paying the lions share. If those rebate coupons were being offered to the payers, I doubt PCMA would be as vocal in their opposition. But generics manufacturers would still have something to say.

GAVI stands for the Global Alliance for Vaccines and Immunization, and serves as a global health partnership aimed at increasing access to immunization programs in poor countries. The success with RTS,S, notes GAVI , is a direct result of public-private partnerships, including the Malaria Vaccine Initiative at PATH, GlaxoSmithKline, and the 11 African research centers conducting the trial.

In fact, pharma companies have been teaming up more and more with academic, nonprofit, and government institutions in recent years to share data  as well as trial best practices and sites.  GSK in particular has been instrumental in the search for treatments of neglected diseases by opening up its patent pool.

Malaria kills more than 700,000 people a year, according to WHO, and requires a global solution to stop its spread. The possibility of adding malaria to the list of diseases for which there are available vaccinations is incredible. Such efforts and partnerships can ideally lend themselves to the fight against other diseases as well in the future.

Read more about global health efforts on PharmTech.com/global+health.

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