From the Editor and Spotlight

BPI Staff

January 13, 2015

10 Min Read

From the Editor
Many publishers are grappling with managing and predicting the course of print and digital publishing. For academic journals with relatively few paid subscribers and/or association members focusing on specialty subject matter, going digital may make good sense — especially if that can lower subscription costs. However, BPI is a hybrid of reviewed journal and trade publication, addressing many reading and advertising preferences. The choice of which content to offer in print and which to duplicate or offer exclusively in digital format is not entirely clear cut to us. Our controlled-circulation business model rests on the economics of print publishing, with formulaic calculations of advertising:editorial ratios and circulation-auditing requirements. But it allows us to meet the information needs of a fairly broad audience spanning science/technology, different functional groups, business, regulatory affairs, and so on — while providing information to advertisers about who our readers are and what they may plan to purchase. It also lets us offer print subscriptions free to qualified readers.

We control our print circulation to predefined groups of 30,000+ readers in North America and Western Europe. And new data show that an additional 50,000+ readers regularly access our issues digitally outside those mailing areas. The work of qualifying those readers (understanding who they are and what they do) is ongoing. But with a readership of 80,000+, we are reaping the rewards of our digital strategies while encountering editorial challenges along the way.

I may be (figuratively) teetering on the tip of an iceberg here: the debates over print versus electronic, and peer-reviewed versus open-source publishing. But I am no Luddite. Times change, language changes, reading habits change, and business models and advertising approaches change. I suspect that the scales may tip in favor of broader, rapid dissemination of electronic information over more costly production of limited-circulation physical copies that sit catching dust. But which format really provides the better, more secure legacy?

Of immediate concern amid these transitions is a loss of version control. It is all too easy to upload a file. But sharing a file online is publishing, even if no ink is involved. Asking for first publication rights, as we do, has been a traditional means of controlling quality through review, subsequent revisions, copyediting, and so on. So if we don’t catch the existence of a previous online publication before we go to print with our edited version, which one should readers cite?

Editors who know their audience seek to make all materials understandable across its range of linguistic and technical levels. Copyediting may be even more important these days, when digital readership can cross the globe almost instantly. How can readers discriminate between what is legitimate technical information and what has gone too quickly to the Internet? We want our print and digital versions to be the same, although we might add supplementary material to an online article.  We want to adapt to new ways of reading and accessing information based on true reader needs — not always easy to determine. And I’ve reworked the author guidelines, copyright forms, and policy descriptions to make our expectations clear about peer review, copyediting, and reprints. This is so authors will know what to expect in working with us. Together, we can prepare your work for the best possible audience that it can reach.


Introducing Our Niche-Disease Series
by Cheryl Scott

A rare or orphan disease affects a small percentage of the population, but with some 7,000 such conditions listed by the Global Genes organization (, they collectively have a significant impact on global health. An estimated 350 million people are affected worldwide — a population that would make up the world’s third largest country all together.

International definitions vary: In the United States, a condition is considered “rare” if it affects <200,000 people; in the United Kingdom, a disease is considered rare if it affects <50,000 citizens. One may be considered rare in a given part of the world but common in another. Most rare diseases (80%) are genetic in origin. Half the affected patients are children, and half the conditions have no devoted research foundation.

Some well-known biopharmaceutical companies are devoted to innovating in the orphan-disease segment: e.g., Alexion, BioMarin, Celgene, Genzyme, Isis, Onyx, Shire, and Vertex. But the vast majority of these conditions (95%) have no FDA-approved treatments. During the first 25 years of the Orphan Drug Act (passed in 1983), 326 such drugs were approved for the US market. Just 350 of the 7,000 orphan diseases are most prevalent — affecting 80% of such patients — and thus the most likely candidates for pharmaceutical intervention. The Health on the Net Foundation lists those online: www. Many of us know someone with a rare disease. For example, my best friend from high school was born with epidermolysis bullosa, which affects one in 50,000 people.

A Big Pharma Approach: Martin Andrews was appointed senior vice president of GlaxoSmithKline for rare diseases in November 2013. At that time, he discussed the program online ( “We aren’t focusing on a particular disease. Instead we’re focusing on innovative technologies and scientific approaches that can be broadly applied to a number of different areas. That includes biopharmaceuticals, oligonucleotides, and gene therapy alongside more traditional small- molecule products.” That sets GSK apart from many other companies involved in niche-disease research, most of which are smaller organizations.

“I hope we will help further understanding of the diseases that we work on, and so help the field to advance,” said Martin. For example, in working on Duchenne muscular dystrophy, GSK gathered the largest clinical dataset related to the condition, which could help the scientific community’s understanding of DMD.

Delivering medicines for rare diseases involves many challenges. “We are often operating in uncharted territory,” Martin explained. Little or nothing may have been published regarding the natural history of a given disease. “This makes establishing meaningful endpoints to evaluate the impact of investigational medicines challenging. We also need to carefully select diseases for which we believe we can make the most difference. But the biggest challenge for anyone working in this area is to be ultraresilient: It is heartbreaking when things don’t go as planned, and you know what that means for patients and their families.”

I further discussed the practicalities of development with BPI editorial advisor Jim Faulkner (vice president of rare-disease CMC manufacturing and supply at GSK). “We are in the fortunate position of having a broad and deep research base,” he said. “Consequently, we can be ‘science-led’ regarding the best opportunities in rare diseases that may emerge from our research in any number of therapeutic areas and technical platforms. Criteria that lead us to progress a candidate into development include high unmet medical need; clearly defined disease etiology and mechanism of action; significant probability that a target can be treated with available technologies; and an ability to synergize development costs with (or ‘repurpose’ candidates that have failed for) other indications.”

I wondered why rare-disease programs seemed to be the purvue of smaller companies. “Many facets of rare-disease drug development do not fit easily with the historical ‘big pharma’ model of industrial scale and mass marketing,” Faulkner explained, “such as a potentially small customer base, specialized supply chains, and nonstandard development pathways. So the history of drug development in rare diseases has been dominated by smaller, more specialized ‘niche’ biotech companies. Fortunately, a number of developments have made the case for investing in a specialized rare disease venture much more persuasive.”

Among those, he listed an increased scientific and genetic understanding of rare-disease etiology. The regulatory environment has evolved to include global orphan drug policies and FDA initiatives such as breakthrough-therapy designation and priority-review vouchers. “Commercially,” he added, “orphan drugs are characterized by enhanced exclusivity protection, lower marketing costs, faster uptake and appropriate pricing.”

So the past decade has seen big pharma making serious entry into the rare-disease space. GSK set up its dedicated team in 2010, Faulkner reports, to “look for creative solutions to deliver potential medicines to patients — whether through our own internal R&D engine, licensing opportunities, collaborative partnerships, or focused investments.”

With smaller potential markets, it seems that chemistry, manufacturing, and controls (CMC) programs in developing orphan drugs would face even more cost pressure than those working on products with larger potential markets. “CMC development of orphan drugs faces a number of particular challenges,” Faulkner agrees. These include specialized supply chains (“often direct to patient”) that necessitate a highly personalized approach. Rapid progression from clinical data to market (often including a compassionate-use program) usually keeps the process used for clinical supply unchanged when a product launches commercially. That necessitates a very integrated approach to research, development, and manufacturing.”

Low-volume production of orphan drugs often limits their batch history, Faulkner adds, making it difficult to build a significant data set of process operating data. “There is a natural marriage between rare-disease indications and pioneering technologies: cell/gene therapies, antisense oligonucleotides, and therapeutic proteins.” Associated manufacturing technologies can be unproven and highly specialized.

“It simply isn’t possible to bear the cost of a full CMC development program of a new technological platform for a very rare disease,” Faulkner explains, “and still make any kind of return on that investment. Fortunately, regulators recognize that difficulty and are willing to work closely with manufacturers to tailor a CMC registration package that’s ‘fit for purpose’ in a disease with high unmet need — without compromising product quality.”

Finally, there is the issue of competition. What if more than one company targets a given condition? “We do increasingly see competition in a few specialized, established rare disease areas,” says Faulkner, “such as lysosomal storage disorders.” But orphan-drug designation establishes a period of exclusivity for companies that are first to market with a particular treatment modality for a specific indication. “The only way that following companies can break that exclusivity period is if their new treatments are significantly different and offer a superior clinical benefit,” Faulkner says. So if a company initiates a new development program for a condition that already has a treatment, it needs clear reason to believe that the new drug really will be better for patients.

Other countries have their own legal provisions that, like the US Orphan Drug Act, incentivize drug development for rare diseases. You can find a comparison of EU, Japanese, Singaporean, and US legislations at Orphanet online: cgi-bin/Education_AboutOrphanDrugs.php. That information is available in French, English, Spanish, German, Italian, Dutch, and Portuguese languages.

Rare Disease Day takes place on the last day of February every year, with an objective of raising awareness among the general public as well as policy- makers, public authorities, industry representatives, researchers, and health professionals. A European campaign began in 2008, the United States joined in 2009, and 2014 saw participation in 84 countries around the world. You can find information about upcoming events and associated partner organizations online at

Watch this space throughout 2015 (and beyond, perhaps) for special briefings on different niche diseases. And I’ll be interested to hear about your companies’ projects along the way. Drop me a note at cscott@

ISPE Extends FOYA Deadline
The International Society for Pharmaceutical Engineering (ISPE) has extended your deadline to submit applications for the 2015 Facility of the Year Awards (FOYA) program to 6 February 2015. These awards recognize the pharmaceutical industry’s accomplishments in facility design, construction, and operation as a means of sharing the development of new applications of technology and cutting-edge approaches. Winning projects set the standard for facilities of the future by demonstrating excellence in project execution, facility integration, innovation, sustainability, process innovation, and operational excellence. You can find more information and apply for consideration online at

Correction: November 2014 Issue 
Diane Paskiet was mistakenly listed as an author on “Sterilization Effects on Elastomer Characteristics and Functionality in Parenteral Delivery Systems” in BPI’s November 2014 issue (pages 28–32). Only Andrea Straka should have been listed. The published article did not include a final round of author changes, but the online version does now.

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