Rita Peters is the former editorial director of 

Pharmaceutical Technology, Pharmaceutical Technology Europe

Rita C. Peters

	There are certain signs that Spring will soon arrive: pitchers and catchers report to baseball spring training, the store shelves change inventory from parkas to pastel clothing, and trade show and conference season moves into full swing. The calendar for the next few months is busy with trade shows, symposia, and conferences addressing all aspects of bio/pharmaceutical manufacturing. Pittcon, DCAT, and the Parenteral Drug Association host events in March. 

	Looking ahead to April, the focus is on INTERPHEX, the annual exhibition for bio/pharmaceutical manufacturing, scheduled for April 21-23 at the Javits Center in New York City. 

, is again sponsoring free educational sessions on tableting, continuous manufacturing, serialization, cell therapy manufacturing, and contract services. All sessions will be presented in the exhibit hall; admission is free to any attendee with an exhibit hall pass. The following is a preview of the topics.


	Jim Miller, founder and president of PharmSource Information Services, will offer a review of the contract services landscape. Topics will include the financial market conditions and consolidation in the CMO market, manufacturing capacity, pricing pressures, changing relationships with bio/pharma companies, and more (April 22, 11 am).

Real-World Serialization: How Good is Your Game Plan?


	Serialization deadlines have been set; however, some companies are waiting to take action. Experts from Optel Vision, CRB Consulting Engineers, Pharma Logic Solutions, TraceLink, OCS Checkweighers, Vetter, and PCI will summarize the latest global regulations, offer concrete estimates of return on investment, and share examples of real-world serialization programs that are already yielding returns (April 21, 11:15 am). 

Developments in Continuous Solid-Dosage Manufacturing


	Continuous solid-dosage manufacturing processes offer the potential for improved quality and higher production efficiency. Doug Hausner, associate director for industrial relations and business development at the Engineering Research Center for Structured Organic Particulate Systems, Rutgers University, will discuss regulatory expectations for continuous processing sensing and control (April 21, 1:15 pm).


	Sharon Nowak, Coperion K-Tron Food &Pharmaceutical Industries, with discuss the optimization of feeding and conveying technologies for difficult flowing pharmaceutical powders. Martin Hack, vice-president and general manager, L.B. Bohle, will discuss fluid bed technologies for improved processing; Fred Murray, president, Korsch America will examine multi-layer tableting technology  (April 21, 2:15 pm).

Succeeding in Cell Therapy Commercialization


	Cell therapy is becoming a crucial area of R&D for more companies. Succeeding in this complex area requires a clear understanding of process needs, and equipment that automates more processes. Experts discuss the issues and how to take a holistic approach from the earliest conceptual stage of any cell therapy project. Speakers include Eytan Abraham, Lonza; Robert Preti, NeoStem; Richard Grant, Invetech; Harvey Brandwein, Pall Corp.; Phil Vanek, GE Healthcare (April 22, 1:15 pm).

	To learn more about these conference sessions, visit 


	In addition to moderating these educational session, the editors of 

 will explore the exhibit hall to learn about the newest technologies, and drug development and processing applications. Please stop by the 

 booth (#1530) to discuss ideas about the industry and your suggestions for topics for future issues of the magazine.

: When referring to this article, please cite as R. Peters, “Agenda: INTERPHEX 2015,” 

Articles

Sessions address cell therapies, tableting, continuous processes, serialization, and more.

Agenda: INTERPHEX 2015

	In releasing its annual list of proposed guidance for industry docments, for 2015, FDA’s Center for Drug Evaluation and Research (CDER) mapped an ambitious agenda for key areas. Of the 90 proposed documents listed on the guidance agenda for 2015, four focus on biosimilarity, 13 on pharmaceutical quality/CMC; and three on pharmaceutical quality/cGMPs. Quality metrics, elemental impurities, and supply-chain security are other key areas targeted for proposed guidances. 

	FDA guidance documents are not legally enforceable, but describe the agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited, FDA notes.

	In December 2014, the International Conference on Harmonization (ICH) released long-awaited revisions to standards for elemental impurities in drug products, 

 Guideline for Elemental Impurities for implementation by regional authorities. In January 2015, the United States Pharmacopeial Convention announced an implementation timeline of January 2018; the European Medicines Agency set implementation for new drug products for June 2016 and existing products for December 2017. FDA has not announced implementation dates, but listed a guidance, 

Elemental Impurities in Drug Products Marketed in the United States

	FDA’s 2015 guidance agenda includes six documents related to the implementation of the Drug Supply Chain Security Act (DSCSA). A December 2014 guidance,

 DSCSA Implementation: Product Tracing Requirements Compliance Policy

, delayed enforcement of regulations for trading partners. Industry players have complained that FDA’s DSCSA-related guidance documents thus far have been limited and fail to answer questions presented by industry.

	Proposed guidances include the following: 

		Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base 

		Appropriate Package Type Terms for Injectable Medical Products Packaged in Multiple-Dose, Single-Dose, and Single-Patient-Use Containers for Human Use 

		Drug Products Containing Nanomaterials Elemental Impurities in Drug Products Marketed in the United States 

		Quality Metrics and Risk-Based Inspections

		Established Conditions: Reportable CMC Changes for Approved Drugs and Biologic Products 

		Microbiological Quality Consideration in Non-sterile Drug Product Manufacturing 

		Specified Biotechnology and Specified Synthetic Biological Products-Annual Report

		Biosimilars: Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009 

		Considerations in Demonstrating Interchangeability to a Reference Product 

		Labeling for Biosimilar Biological Products 

		Statistical Approaches to Evaluation of Analytical Similarity Data to Support a Demonstration of Biosimilarity

Pharmaceutical Quality/Manufacturing Standards (CGMP) 

		CGMP Data Integrity Questions and Answers 

		Current Good Manufacturing Practice for Outsourcing Facilities (Pharmacy Compounding) 

		DSCSA Implementation: Annual Reporting by Prescription Drug Wholesale Distributors and Third-Party Logistics Providers 

		DSCSA Implementation: Products Eligible for Grandfather Status 

		DSCSA Implementation: Standards for the Interoperable Exchange of Information for Tracing Certain Human, Finished Prescription Drugs-Standardization of Data and Documentation Practices 

		DSCSA Implementation: The Product Identifier for Human, Finished, Prescription Drugs 

		DSCSA: Verification Systems for Prescription Drugs 

		DSCSA Implementation: Waivers, Exceptions and Exemptions from Product Tracing Requirement.

	A complete list of proposed guidance documents is available on www.fda.gov. For draft and final guidances, FDA offers an 

 to facilitate access to guidance documents. Users can search for documents by keywords, then filter results by product, date issued, FDA organizational unit, type of document, subject, draft or final status, and comment period.

When referring to this article, please cite it as:
	R. Peters, “FDA Sets Agenda for 2015 Guidance Development," 

Biosimilars, supply chain security, quality metrics, and elemental impurities headline guidance topics on FDA’s 2015 agenda.

FDA Sets Agenda for 2015 Guidance Development

	Although the stated mission of all players involved in drug development is to provide life-saving therapies for patients, conflicting objectives and business strategies often get in the way. Getting special interest groups to agree on the best course for providing effective, cost-efficient drugs is similar to trying to get the US Congress to agree on anything. If efforts to accelerate drug discovery, development, and delivery are to advance, various industry segments and both parties in Congress will have to negotiate a compromise to best serve patients.

	For nearly a year, a bipartisan effort by the Energy and Commerce Committee of the US House of Representatives solicited ideas and comments from patients, providers, innovators, regulators, and researchers on ways Congress can help accelerate the discovery, development, and delivery of new treatments and cures. In late January 2015, the committee released a “discussion draft” of a proposed 21st Century Cures Act.

	The discussion document includes ideas from Republicans and Democrats that would incorporate patient perspectives into the regulatory process and help address their unmet medical needs; streamline clinical trials; support continued innovation at federal public health agencies; and modernize medical product regulation. The initiative to accelerate the development of needed therapies for patients is well intended. Once the ideas enter the policy fray, however, best intentions can become political talking points that are distorted in the positioning efforts of competing special interests. 

Incentives for difficult-to-develop therapies and cures


	One major focus of the initiative is designed to encourage bio/pharmaceutical companies to develop therapies for complex diseases such as Alzheimer’s, where the steep investment required to bring treatments and cures to market discourages many efforts.

	A proposed Dormant Therapies Act would reward the development of treatments and cures for patients with unmet medical needs. Innovators would receive a fixed-year protection period for therapies upon FDA approval. “This change would shift research and development toward therapies based on scientific promise and patient need, rather than patent life. It also would reward investment in treatments and cures for complex diseases where it takes longer to develop safe and effective therapeutics,” according to Subtitle L of the discussion draft. 

	A longer patent life could increase the potential profit of a therapy for the innovator, but delay the introduction of generic versions. It also could result in higher prescription drug costs for patients.


	Although the document was not a formal legislative proposal when released, it elicited strong reactions and some posturing from special interest groups.

	The Pharmaceutical Research and Manufacturers of America, which represents innovator pharmaceutical development companies, said the organization supported the committee’s goal of accelerating drug development and would review the nearly 400-page discussion draft and provide additional comments.

	A statement from the Biotechnology Industry Organization noted that several of the organization’s priority suggestions were incorporated in the discussion draft, including the need for a research commitment to study precursors and signs of disease and disease risk factors for chronic conditions. 

	The Generic Pharmaceutical Association issued a statement saying it was “deeply disappointed” in the discussion draft and expressed reservations about the Dormant Therapies provision, saying it “would potentially grant brand drug companies an unprecedented increase in exclusivity for a curiously broad category of new drugs, delaying the competition from generic drugs and biosimilars that promotes beneficial innovations in treatments.”

	The discussion document may be introduced as legislation later this year; however, any progress must overcome competing special interests in industry and Congress. It will be interesting to see how patient well-being will be considered in the process.

When referring to this article, please cite it as:
	R. Peters, "Cures Require Compromise," 

Initiatives to speed drug development must pass Congress and special interest groups.

Cures Require Compromise

	As 2014 drew to a close, FDA reported a number of milestones in drug approvals. Through early December, the agency had approved 35 new molecular and biologic entities, up from 27 in 2013; this total was the second highest number of approvals in a single year in the past decade. Biologics, with 10 approvals, represented nearly one-third of all approvals (1).

	Patients with rare diseases benefited from a record number of novel drugs entering the market in 2014. The 15 drugs approved were the most in a single year since the Orphan Drug Act was enacted in 1983.

	FDA Commissioner Margaret Hamburg noted in the FDA blog (2) that 15 of the approvals were first-in-class drugs, an indicator of their potentially strong clinical impact.

	Hamburg noted that three new approvals were for antibacterial drugs-Dalvance (Durata Therapeutics), Sivextro (Cubist Pharmaceuticals), and Orbactiv (The Medicines Company)--to treat skin infections, specifically acute bacterial skin and skin structure infections. From 2004 to 2013, only five new systemic antibacterial drugs were approved, FDA reports.

	FDA also issued a report card of its own performance. Hamburg cited FDA’s expedited development and review programs--fast track, priority review, accelerated approval, and breakthrough therapy designation-as being instrumental in moving drugs more quickly to market. More than half of the drugs (57%) were approved under priority review; 37% received fast-track designation. “Early and repeated communications with sponsors have also been helpful in speeding these products to market,” she wrote in the blog.

	Hamburg noted that 34 of the 35 drugs approved as of Dec. 3, 2014 were approved before or on their Prescription Drug User Fee Act review goal date; 23 of the 35 drugs were available to patients in the United States before they were available to patients in Europe. Another indication of performance improvements, noted John Jenkins, director of the Office of New Drugs (OND), Center for Drug Evaluation and Research (CDER), is that more submissions are moving through the review process in just one review cycle (1).The review and approval process still has room for improvement. The pace of requests for breakthrough designation have remained steady, however, of the 211 breakthrough therapy requests, 49% were denied; 6% were pending; and 15% were withdrawn. FDA plans to issue further guidance to clarify subjective statutory criteria and basic standards needed for breakthrough requests.

	Jenkins said that manufacturing development and scale up must be accelerated, and noted that several approvals, while expedited or on time, were delayed due to the need to address manufacturing issues.


	CDER’s Office of Pharmaceutical Quality (OPQ) goes live in January 2015, as a single unit dedicated to product quality. FDA expects the OPQ to better align all drug quality functions at CDER, including review, inspection, and research for domestic and foreign drug manufacturing sites.  This “super-office” will bring all non-enforcement-related drug quality work into one office, creating “one quality voice and improving our oversight of quality throughout the lifecycle of a drug product,” as described on www.fda.gov. Janet Woodcock, director of CDER, will serve as acting director.


	1.  J. Jenkins, CDER New Drug Review: 2014 Update, presented at FDS/CMS Summit (Washington, DC, Dec. 11, 2014).
	2.  Margaret A. Hamburg, 

2014 Drug Approvals: Speeding Novel Drugs to the Patients Who Need Them

: When referring to this article, please cite it as R. Peters, " Breakthroughs, with Some Reservations," 

New designations lead to faster drug approvals, but there is more work to be done.

Breakthroughs, with Some Reservations

	According to the industry group PhRMA, the average annual total compensation for biopharmaceutical workers in 2011 was $110,490, almost twice the average salary earned by all US workers (1). An American Association of Pharmaceutical Scientists survey lists the mean annual base salary for pharmaceutical scientists in the US, as of July 2014, as $143,800 (2).
	
	On paper, these salary numbers are impressive. However, the number of research, development, manufacturing, sales, and other positions eliminated in the bio/pharma industry, more than 155,000 since 2009 (3), is sobering. What is the current employment picture for those professionals working in the bio/pharmaceutical development and manufacturing segments? In this issue, the editors of 

 address employment, compensation, workload, training, and other factors in our annual employment survey on pages 20-23.

		Almost 54% of the respondents are contracted to work 40 hours per week; nearly three-quarters of those surveyed say they work more than 40 hours.

		The positions require a variety of skill sets, including knowledge of regulatory practices, chemistry, analytical techniques, and statistics.

		The respondents were experienced: 66% have more than 15 years of experience in the industry.

		For the most part, the respondents are not impressed with the training for people newly hired for the industry; 78% said the new hires were adequately trained, but not exceptional.

		More than 60% reported a salary increase from 2013 to 2014, Of the 50% of the respondents who received a bonus, one-quarter received larger bonuses than the previous year.

		More than 80% received at least two weeks of vacation time; however, 80% of the respondents said they spent at least part of their vacation time doing work.

	In evaluating factors other than compensation, more than three-quarters of the respondents said they did not experience discrimination; their skills were used to the fullest extent; and their work was valued by their employer. Some respondents, however, saw limited opportunities for professional development (35%) and career advancement (40%).
	
	When considering a job change, salary is the top consideration, respondents report, followed by professional advancement and job security. Intellectual challenge and work/life balance are other top considerations.

	Salary is not the main reason respondents come to work, however. Challenging projects, intellectual stimulation, a good work/life balance, supportive management, and job security were the top reasons cited.

	Overall, the respondents were tolerant of negative workplace factors; less than 15% percent identified a specific factor as a reason to quit their job. Low pay was the second leading contributor to job dissatisfaction, behind budgets that are too low to accomplish tasks. Negative workplace attitudes, issues with management, and discrimination were other top concerns.

 team, I thank all bio/pharmaceutical professionals for their contributions to the industry and extend our best wishes for a prosperous and successful 2015.

	References
	1. PhRMA, “The Biopharmaceutical Industry Helps Strengthen the U.S. Economy”, www.phrma.org/economic-impact, accessed Nov 24, 2014.
	2. AAPS, 

, (Arlington, VA, 2014).
	3. P. Loftus, M. Falconi, H. Plumridge,“In Drug Mergers, There’s One Sure Bet: The Layoffs”,

l, April 29, 2014, accessed Nov. 24, 2014.

 When referring to this article, please cite it as R. Peters, "The BioPharma Working Life," 

Professionals share the ups and downs of working in the bio/pharma industry.

The Bio/Pharma Working Life

Ebola virus disease (EVD), which first appeared in Africa 38 years ago, generally was perceived by people in developed nations as a scary, deadly, but distant illness far removed from their lives.

EVD is a severe, often fatal disease that is transmitted human-to-human through bodily fluids. According to World Health Organization (WHO) data, nearly 2000 people in Africa were infected with EVD from 1976 through 2013 with an average fatality rate of 50%. The latest outbreak began in March 2014 in Guinea and spread to Sierra Leone, Liberia, Senegal, and Nigeria. As of Oct. 14, WHO reported 9216 confirmed, probable, or suspected cases of EVD worldwide and 4555 deaths.

When the first patient with EVD walked into a US hospital, the facility was not prepared; two nurses treating the patient were infected. Despite initial missteps, federal and local officials contained the outbreak to that single hospital. But it was too late to contain overreaction by the public, press, and politicians, which spread much faster and wider than the disease itself and distracted public attention from real health threats.

While the afflicted nurses battled the disease, politicians lined up to criticize the reaction of the federal government. Demonstrators outside the White House called for a halt to flights from West Africa. Schools closed. In one extreme example of undue caution, a school in Maine placed a teacher on a 21-day leave after she attended a conference in Dallas in mid-October, even though she had no contact with any people, transportation, or facilities involved in three EVD cases diagnosed in that area.

The 2014 outbreak clearly illustrates there is a need for effective vaccines and therapies for EVD; a handful of vaccines and treatments are in early development and testing stages. Questions remain, however, about the bio/pharma industry’s ability or desire to develop and produce therapies or vaccines cost-effectively.


While EVD generated alarm, two other health issues presented serious medical challenges for US patients.

Between mid-August and mid-October, the Centers for Disease Control (CDC) and state public health laboratories confirmed that 825 people, mostly children, in 46 states and the District of Columbia had respiratory illnesses caused by enterovirus D68 (EV-D68); seven patients died. Enteroviruses and rhinoviruses cause millions of respiratory illnesses in children each year; however, the 2014 outbreak of EV-D68 was much greater than that reported in previous years. There are no vaccines to prevent EV-D68.

Influenza is an annual threat to the health of the general public and patients with compromised medical conditions in particular. The October to March flu season is just underway and CDC estimates that 5-20% of Americans get the flu each year. While most people recover, CDC estimates that between 3000 and 49,000 Americans die from the flu or its complications every year.

The flu virus is contagious and, unlike EVD, can be spread through airborne transmission (a cough or sneeze) and by someone infected with the virus who is not showing symptoms. Unlike EVD and EV-D68, however, vaccines to protect against the flu are readily available; CDC says the vaccine reduces the chance of getting the flu by approximately 60%. Still, less than half of the US population gets innoculated.

Count me among those lining up for an annual flu shot. The vaccine does not come with a guarantee that I will avoid the flu, but a shot of prevention is worth more than a pound of paranoia.


Rita Peters is the editorial director of 

Ebola Virus Disease (EVD) is a severe, often fatal disease that is transmitted human-to-human through bodily fluids.