Rita Peters is the former editorial director of 

Pharmaceutical Technology, Pharmaceutical Technology Europe

Rita C. Peters

brand of print and online publications are pleased to present our annual 

 supplement, which includes a special CPhI Worldwide 2015 Planning Guide. This issue combines technical articles on leading pharma industry topics and a comprehensive 

preview of the upcoming CPhI Worldwide trade show

brand has provided authoritative, technical, and highly respected articles, peer-reviewed research, news, analysis, and commentary for bio/pharmaceutical development and manufacturing professionals around the world. Pharmaceutical Technology magazine provides readers in North America with similar content, while keeping a close watch on FDA regulatory concerns. 

 magazine, now in its 26th year of publishing, delivers monthly updates on the latest trends and practices in bio/pharma development and manufacturing, with a focus on the European markets.

	Online, PharmTech.com provides daily updates of breaking news from the technical, scientific, regulatory, and business sectors of the bio/pharma industry. Readers around the globe stay informed through weekly and monthly newsletters on a range of topics.

 brand’s strength in the bio/pharma arena and global audience proved a natural fit with the CPhI brand of trade shows--including CPhI Worldwide (Oct. 13-15, Madrid, Spain)--when UBM plc, organizer of CPhI, acquired Advanstar Communications, the parent company of the PharmTech brand, in 2014.

	Our research reveals that bio/pharma professionals turn to different media channels--print, online, webcasts, trade shows, newsletters, content marketing, and more--to solve their most difficult drug development and manufacturing challenges. We believe the new relationship with CPhI is a prime opportunity to make PharmTech’s content available to a broader bio/pharmaceutical market.

	We invite you to explore this supplement, view more content on PharmTech.com, subscribe to the 

newsletters, and meet us in person at CPhI Worldwide at Stand 1A3.

	Rita Peters, Editorial Director
	Adeline Siew, PhD, Editor
	Michael Tracey, Publisher
	Chris Lawson, Associate Publisher

Pharmaceutical Technology APIs, Excipients, and Manufacturing Supplement

:
	When referring to this article, please cite it as R. Peters et al, "The PharmTech/CPhI Connection," 

APIs, Excipients, and Manufacturing Supplement

Articles

This special issue combines technical articles on leading pharma industry topics and a comprehensive preview of the upcoming CPhI Worldwide trade show

The PharmTech/CPhI Connection

	In July 2015, Stephen M. Ostroff, acting commissioner of FDA, marked the third anniversary of the Food and Drug Administration Safety and Innovation Act (FDASIA) by citing the agency’s achievements in promoting drug safety, accelerating drug approvals, improving stakeholder involvement, and securing the supply chain (1).

	Ostroff noted that since 2012, the agency has issued more than 35 draft and final guidance documents and more than 10 proposed and final rules. The number of drug shortages dropped from 282 in 2012 to 101 in 2014, an improvement attributed to FDA action.


	The FDASIA provision to create the Breakthrough Therapy designation may be the most significant. Ostroff noted that as of June 2015, FDA had received 315 requests for the special designation, and 93 drugs and biologics had been granted breakthrough status. To date, 26 breakthrough therapy drug/indication combinations have been approved and are on the market providing treatments for both rare diseases and common conditions.

	FDASIA also gave FDA new authorities to protect the US drug supply chain, improve communication and enrollment in clinical trials, and increase patient engagement.

	In a separate whitepaper (2), FDA noted that improvements in the final stage of drug development have reduced drug approval times. The United States leads the world in the introduction of novel drugs, FDA reports, giving Americans first access to new treatments and cures.


	Overall pharmaceutical productivity has fallen, however, because the cost of getting a drug from discovery to submission of a marketing application has escalated and failure rates have grown, FDA reports in the whitepaper. Despite advances in developing targeted medicines for cancer and HIV/AIDs, an “inadequate scientific understanding of specific diseases is likely to remain the most important limiting factor for developing targeted therapies in other areas” (2).

	The whitepaper noted FDA’s activity to “modernize and speed the earlier phases of drug development” through collaborations on the science of biomarkers and surrogate endpoints and working with drug manufacturers and patient groups on clinical trial design. Efforts by industry groups to work together are necessary and commendable. The bottom line, however, is that funding to conduct the research is needed.

	Ostroff noted the importance of user fees to meet the agency’s responsibilities, in light of budgetary challenges. FDA kicked off efforts for the next reauthorization of the user fee programs, holding stakeholder meetings in June 2015. In addition, discussion about the 21st Century Cures Act has directed attention to the ongoing need for disease and drug research and renewed the debate of who will pay for the associated costs.

	Special interest groups-including the Pharmaceutical Research and Manufacturers of America, Biotechnology Industry Organization, Generic Pharmaceutical Association, and the Pharma and Biopharma Outsourcing Association-are expected to offer statements, testimony, press releases, and interviews positioning their members’ interests. Patient groups also offered their perspectives. Throw in the polarized factions in Congress and presidential hopefuls, and the upcoming debates should be interesting.

Celebrating the 3rd Anniversary of the FDA Safety and Innovation Act

, online July 9, 2015, accessed July 27, 2015.
	2. FDA, “Targeted Drug Development: Why Are Many Diseases Lagging Behind?” Whitepaper (Rockville, MD, July 2015).

:
	When referring to this article, please cite it as R. Peters. “The Bottom Line on Pipeline Progress,” 

FDA notes progress in drug development, but cites scientific and funding roadblocks.

The Bottom Line on Pipeline Progress

	At the 2015 Biotechnology Industry Organization (BIO) convention, held in Philadelphia in mid-June, all indicators showed that the industry was riding a record wave of success.

	According to a BIO post-event press release (1), more than 15,800 industry players from 69 countries, 47 states, the District of Columbia, and Puerto Rico attended. A record number of partnering meetings-27,279 meetings between 3100 companies-illustrated the convention’s business focus.


	Business was good for the biotech industry in 2014; in fact, it was a record-setting year, reports Ernst & Young (E&Y) in its 29th annual report, 

Beyond Borders, Biotechnology Industry Report 2015

 (2). The report cites record revenues, profitability, financing, and drug approvals as signs of a healthy market.

	In the established biotech areas of the United States, Europe, Australia, and Canada, revenues increased 24% in 2014; R&D spending increased by 20%. A robust stock market and large number of initial public offerings pushed the biotech industry capitalization in the US to more than $1 trillion for the first time, E&Y reports.

	The report authors, however, warned that the biotechnology industry cannot afford to become complacent, but must work with patients, payers, providers, and governments to develop new products for unmet medical needs, as well as ways to improve care delivery and health outcomes. The industry must also play a role in developing payment schemes to give patients better access to breakthrough drugs.


	In a keynote discussion, Tom Brokaw, the award-winning journalist, reiterated the need for a discussion about patient access to crucial drugs. A long-time observer of US business, politics, culture, and society, Brokaw has added first-person experience as a patient undergoing treatment for multiple myeloma. 
	Brokaw noted that patients, drug companies, and doctors do not speak the same language. The nation, he says, needs an all-inclusive health plan that makes the price of drugs affordable to all.

	To achieve this, the US needs a “big idea” debate on healthcare, Brokaw said. However, in the current American political system, there are no big ideas. Partisan politics, cable news, social media, and professional and amateur political commentators contribute to a lack of direction and desire to solve the nation’s pressing issues.

	To illustrate how the desire to achieve a “big idea” requires cooperation and sacrifice, Brokaw recounted the efforts of US paratroopers in the D-Day invasion of Europe in 1944. When the soldiers dropped behind enemy lines in France, they were separated from their units and were scattered across the countryside. They assembled with others near them to form makeshift units and accepted their new orders. The soldiers did not stop to argue about what platoons or units the fighters were from; they simply went about the business of liberating Europe, a “big idea” of those times.

, Brokaw related that the soldiers who fought in World War II did so because it was the right thing to do.

	The current generation of politicians, payers, patients, and drug companies are challenged with determining “the right thing to do” to achieve one of today’s “big ideas”--affordable, effective drug therapies for all patients. This time, the enemy may be us.


	1. Biotechnology Industry Organization, “The 2015 BIO International Convention Closes in Philadelphia,” Press Release (Philadelphia, PA, June 18, 2015).
	2. Ernst & Young, 

:
	 When referring to this article, please cite it as R. Peters. “Big Ideas Demand Big Action,” 

The bio/pharma industry enjoys success, but it cannot ignore patient access to medications.

Big Ideas Demand Big Action

	FDA’s Center for Drug Evaluation and Research (CDER) has been encouraging industry to invest in quality drug production methods and improve processes, facilities, and equipment. Such advances in processing are built on an exchange of scientific and technical information.

	Players in bio/pharmaceutical development and manufacturing-from bio/pharma companies and industry suppliers-have a wealth of scientific and technical expertise about biopharmaceutical formulation, development, and manufacturing. Sharing this knowledge-in an objective format-is vital to the growth and improvement of the bio/pharma industry.

magazine has taken a leadership role in sharing information about bio/pharmaceutical formulation, development, and processing methods, technologies, and practices. With a dedication to providing objective, informed content, the magazine and 

 are excellent media channels for this information exchange. 

	Article formats vary from peer-reviewed papers, non peer-reviewed technical papers, and business-focused articles. The editors welcome contributions from experts in the bio/pharmaceutical development community. All contributions, both peer-review submissions and technical articles, should be written with the following four guidelines in mind.


	Articles and papers must be based on technical and scientific fact, supported by references to published literature or data. Marketing-based language, unsupported claims, or promotional language are not acceptable in editorial features. 


	Manuscripts are reviewed with the understanding that the content has not been published previously in any format, including print or electronic publications, conference proceedings, whitepapers, application notes, posters, or company-created marketing or sales literature. The article submission should not be ghostwritten. In addition, it should not be under consideration for publication with any other print or digital publication, in any language. 


	The author must own the rights to the submitted content, including all images, tables, and figures. Graphics from other sources or third-party sources will not be accepted for publication. Before a manuscript is accepted for publication, all authors must sign a license agreement to provide Pharmaceutical Technology permission to publish the original article and its associated figures/tables in print and online. Authors retain the copyright to the article, as it was originally submitted.


	The editors seek objective articles on technical and regulatory subjects including process development, manufacturing, formulation, drug delivery, API synthesis, analytical technology and testing, primary packaging, IT, outsourcing, supply chain, serialization, and regulatory compliance. Consult the editorial calendar for a list of current topics. Upcoming topics include taste masking, drug reformualtion, combination products, parenteral manufacturing and process controls.

	If you have an important technical, regulatory, or process improvement topic to share with peers in the industry, I encourage you to share it through 

 and review the author’s guidelines and editorial calendar. Then, send me a message or give me a call. I would be happy to discuss your ideas for objective editorial contributions.

: When referring to this article, please cite it as R. Peters, " Help Build Better Bio/Pharma Processes," 

Peer-reviewed papers and technical articles can help advance bio/pharmaceutical development.

Help Build Better Bio/Pharma Processes

	A recent report from the Pharmaceutical Research and Manufacturers of America (PhRMA) lists impressive contributions of biopharma companies to patients, healthcare, and the economy. The report, 

2015 Biopharmaceutical Research Industry Profile

 (1), indicates that in 2014, PhRMA member companies spent an estimated $51.2 billion in research and development, down slightly over the 2013 level of $51.6 billion. The estimates, gathered in a recent survey of PhRMA member companies represent “the majority of all biopharmaceutical spending-both public and private-in the United States,” PhRMA reports (1).

		Biopharmaceutical companies on average invest as much as six times more in R&D-relative to sales-than the average US manufacturing firm.

		The pharma industry supports 3.4 million jobs in the United States, 810,000 through positions through direct employment.

		The overall impact of the sector on the domestic economy is $789 billion annually.

	The report emphasized the value that the biopharmaceutical industry provides to patients and society; however, it failed to look at manufacturing-related shortcomings that can impact patient health. Prescription drugs, which represent only nine cents per 2013 healthcare dollar, “play a central role in improving the health outcomes of patients” when used appropriately, PhRMA reports, but limited access to medicines and complexity of treatment regimens, however, are barriers to the optimal use of medicines. Two other threats that limit patient access to drugs and pose health risks were not mentioned in the report: drug shortages and counterfeit drugs. 

	While the number of new drug shortages has dropped off since peaking in 2011, ongoing shortages persist. With a limited number of manufacturing lines available to produce generic drugs, especially injectable drugs, there is little margin for error.

	Quality problems (40%) were the most-frequently cited cause for all drug shortages from January 2011 through June 2013, according to a US General Accountability Office report (2). Manufacturing delays and capacity issues involving shutdowns or slowdowns of facilities to perform maintenance or remediation were cited in another 30% of the drug-shortage cases. API-related problems contributed to 9% of the drug shortages. In addition, 12% of drug shortages were due to product discontinuation, a business decision.

	Counterfeit medicines present another quality issue, both within and beyond US borders. According to the National Institutes of Health (NIH) “Poor quality medicines are a real and urgent threat that could undermine decades of successful efforts to combat HIV/AIDS, malaria, and tuberculosis” (3).

	Implementation dates for serialization-the first step in track-and-trace efforts to reduce counterfeit and falsified medicines-are not far off, but many companies have been slow to take action, reported experts at 

 seminar at INTERPHEX 2015 in mid-April.

	FDA has actively addressed the drug shortage issue, promoting risk assessment, quality metrics, and facility and equipment improvements. Industry associations, including the Parenteral Drug Association and International Society of Pharmaceutical Engineers, have championed the cause of quality improvement. The wheels of change turn slowly, however, and are hampered by regulatory and operational hurdles, as well as business decisions to delay improvements.

	Statistics can be presented to paint any performance picture. Patient safety, through drug quality and serialization efforts, need to be figured into the bottom line.

 (Washington, DC, 2015).
	2. General Accountability Office, “Drug Shortages, Public Health Threat Continues, Despite Efforts to Help Ensure Product Availability” (Washington, DC, February 2014).
	3. National Institutes of Health, “Global pandemic of fake medicines poses urgent risk, scientists say,” Press Release (Bethesda, MD, April 20, 2015).

Vol. 39, Issue 4
	Page: 12
	Citation: When referring to this article, please cite as R. Peters, “Completing the Report Card,” 

Pharma can boast of big-picture successes, but needs to work on operational issues.

Completing the Report Card

	Approvals of most generic drugs receive little fanfare. FDA’s approval of the first US biosimilar produc-Zarxio (filgrastim-sndz) from Sandoz-in March, however, garnered a wealth of media and public attention. A biosimilar to Amgen’s Neupogen (filgrastim), which was originally licensed in 1991, Zarxio is approved for the same indications as Neupogen and may be prescribed by a healthcare provider for patients undergoing cancer treatments or those with neutropenia.

	The approval of the first biosimilar comes five years after the enabling legislation, the Biologics Price Competition and Innovation Act of 2009, was passed as part of the Affordable Care Act that was signed into law in March 2010.

	Janet Woodcock, director of the Center for Drug Evaluation and Research described the Zarxio approval as 'a significant milestone in FDA’s regulatory histor" (1). She noted that the initial approval paved the way for future biosimilar approvals, and a successful review process could provide more affordable treatments to patients and spur development of a new segment of the biotechnology industry.


	The approval marked a turning point for the biopharmaceutical industry; however, it also is an indicator of how the United States lags the rest of the world in biosimilar development and use. Regulatory pathways for biosimilar approval have been established in other parts of the world for some time. The Zarxio approval comes nearly a decade after the first biosimilar drug was approved in Europe; in fact, biosimilar filgrastim is available in more than 60 countries worldwide.

	Questions about the development and acceptance of biosimilar drugs remain:

	On the patient level, the decision to switch from a branded biologic to a biosimilar is up to the prescriber; however, the potential for immunogenicity due to the change in biologic product is a concern.

	Analytical studies to evaluate similarity can be challenging and applications must have sufficient analytical data.

	The naming convention for biosimilar products is a hot topic for manufacturers and healthcare providers. While FDA works on draft guidance for the naming of biosimilars, a placeholder nonproprietary name--filgrastim-sndz--is used to identify the product. A guidance document for biosimilar labeling is also in the works.

	While Sandoz has a green light from FDA to move forward with Zarxio, pending legal action threatened to delay the market release in early April.


	While March marked a new beginning for FDA with the biosimilar approval, it also marked the end of the six-year tenure of Margaret Hamburg as FDA commissioner.

	When Hamburg announced that she was stepping down in February, the news generally was met with praise for FDA accomplishments during her tenure including an increased emphasis on science-based regulation, efforts to streamline product approvals, and addressing challenges of operating in a globalized drug market.

	Addressing the unresolved and unknown challenges in the biosimilar era-along with many other issues facing the agency-will be left to the next FDA commissioner.

	I would like to thank Dr. Hamburg for her service and urge the President and Senate to act swiftly to appoint and approve a successor.


	1. J. Woodcock, CDER Center Director e-mail, March 6, 2015.

: When referring to this article, please cite as R. Peters, “Welcome to the Biosimilar Era,” 

FDA approves a biosimilar and loses a commissioner in March.