Rita Peters is the former editorial director of 

Pharmaceutical Technology, Pharmaceutical Technology Europe

Rita C. Peters

	The end of the year is the traditional time to assess achievements and shortfalls of the past 12 months. A preliminary review of the bio/pharma industry accomplishments shows some impressive results. By the end of November 2018, FDA had approved 53 novel drugs, setting a pace for the most approvals on record.

	The approvals included notable advances in science and targeted medicine. On November 26, FDA approved Vitrakvi (iarotrectinib), the second cancer treatment approved based on a biomarker for different types of tumors rather than tumors originating in a specific organ or part of the body. The therapy is the first to receive a tumor-agnostic indication at the time of initial FDA approval (1).

	In announcing the approval, FDA Commissioner Scott Gottlieb noted that the therapy marked “a new paradigm in the development of cancer drugs that are ‘tissue agnostic.’” Gottlieb also credited increased knowledge of cancer mutations, breakthrough therapy designation and accelerated approval processes, and a modern framework of clinical trial designs as contributing to more targeted and effective cancer treatments.

	While the approvals marked progress in innovation, the global recall of the API valsartan due to the discovery of impurities N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in drug products raised questions about the quality of drug substances in the supply chain.

	Quality problems were a mixed bag this year. The number of warning letters issued by FDA were on a slightly slower pace compared with 2017; however, the number of drug recalls were up.

	While innovative achievements such as new drug approvals get the headlines and are recognized and rewarded, quality programs are essential but rarely get attention until something goes wrong. In this issue, and in supplemental online coverage, the editors present multiple views of quality issues throughout the drug development and manufacturing continuum.

: Representatives from global bio/pharma answer key questions about an enhanced approach to the lifecycle of an analytical procedure based on practical experience of applying these concepts to real projects.

: Consultants and experts in risk assessment share best practices that will help ensure the quality of APIs, ingredients, and process aids and materials.

: The handoff from inventor to contract development and manufacturing organization partner, depends on communicating the right information at the right time. This article examines recent failures and lessons learned.

: FDA warning letters often refer to training deficiencies. Learn the underlying technical and cultural reasons and why it can be difficult to tie employee training programs to business objectives.

: Learn how non-compliance can exacerbate drug shortages and how it can play into affordable healthcare.

	The editors regularly add features, news, and reports on a range of quality issues to the 

. Recent additions include mock inspections, eliminating obsolete heavy metals test, and lot release testing. Bookmark 

 for quick access to the latest bio/pharma quality topics.

	1. FDA, “FDA Approves an Oncology Drug That Targets a Key Genetic Driver of Cancer, Rather Than a Specific Type of Tumor,” Press Release, Nov. 26, 2018.

	When referring to this article, please cite it as R. Peters, “The Key Word: Quality," 

Articles

Bio/pharma companies cannot spell success without solving all elements of quality programs.

The Key Word: Quality

Proteins must be characterized at many phases of biopharmaceutical research, development, and manufacturing, each with differing demands and requirements. Instrument capabilities-and limitations-influence the speed and success of development efforts. Researchers from biopharma, contract service organizations, and academia face challenges of selecting and optimizing appropriate techniques for protein characterization needs.

 shared similar concerns about the need to conduct complex protein characterization studies under the pressures of tight timelines and urgency to get new drug products to clinic and approval.

Bio/Pharma Laboratory Best Practices 2018 

	When referring to this article, please cite it as R. Peters, "Complex Protein Studies Demand Dynamic Techniques," 

Pharmaceutical Technology Bio/Pharma Laboratory Best Practices 

By adapting techniques from other sciences-and exploring better tools for biologics drug development-researchers are addressing challenges of protein characterization.

Complex Protein Studies Demand Dynamic Techniques

	Using the annual CPhI Worldwide tradeshow as a benchmark, the bio/pharma industry appears to be healthy and growing. Organizers of the 2018 event, held Oct. 9–11 in Madrid, Spain, reported attendance has increased by 9000 attendees compared with the last CPhI event in Madrid in 2015. Nearly 44,500 participants from 164 countries visited the three-day event, which included more than 2,500 exhibits, conference sessions, and networking opportunities (1).

	Opinions about industry prospects around the globe also were revealed. In an annual study released during the event (2), CPhI reported results of a survey of bio/pharma professionals that ranked India, the United States, and China as the top regions for predicted pharma market growth. The US ranked first of 10 countries evaluated for reputation, followed by Germany, Japan, the United Kingdom, and France. India was ranked sixth; China was ranked last.

	CPhI also measured perceptions of the knowledge of bioprocessing professionals, innovation, and quality with the US ranking first, followed again by Germany, Japan, and the UK. In a measure of growth potential, Ireland-home to planned expansions of bioprocessing capacity-ranked third.

	In addition to the industry data, innovative technologies and services that support bio/pharma development, manufacturing, and distribution were recognized at the 2018 CPhI Pharma Awards Gala, held on Oct. 9, 2018.

	The winners were selected from 139 finalists in 17 categories including drug formulation, manufacturing, materials, packaging, drug delivery, patient compliance, contract services, pharma company of the year, and CEO of the year. The finalists were selected from more than 250 entries. The winners are as follows:

-MiVital AG, Micelle Inside Solubilization

-Merck, Simplification of Fed Batch Processes Using Modified Amino Acids

-Tornado Spectral Systems, HyperFlux PRO Plus, Tornado Spectral Systems

-Nemera , e-NOVELIA, smart ophthalmic add-on. Highly commended: Stiplastics, Stiplastics

- CatSci Ltd, Development of a novel bio-catalyzed manufacturing route for a generic API. Highly commended: Cambrex, Continuous Flow Centre of Excellence

-Technoflex, Dual-Mix. Highly commended: Aptar Pharma, QuickFlip

Supply Chain, Logistics, and Distribution

-West Pharmaceutical Services, Inc., Delivering on the Promise of Good Corporate Citizenship

-Medical Brands and Vemedia, Excilor 2-in-1 Wart Treatment Device

-SRS Life Sciences Pte Ltd, SRS Unistraw Delivery System

	Congratulations to the awards finalists and winners. Information about select winning technologies will be published in future issues of 

	1. CPhI, “Global pharma set for strong year with record 164 countries and 44,500 attendees at CPhI Worldwide,” Press Release, Oct. 22, 2018.
	2. CPhI, “CPhI’s Pharma Industry Rankings: A Snapshot of Pharma’s Health,” CPhI Annual Industry Report, October 2018.


	Vol. 42, No. 11
	November 2018
	Page: 10

	When referring to this article, please cite it as R. Peters, " Innovation and Industry Strength Recognized at CPhI," 

Survey results and record attendance show positive signs for various bio/pharma regions.

Innovation and Industry Strength Recognized at CPhI

	If companies make pre-competitive advances on manufacturing processes, noted Peter Marks, director of the Center for Biologics Evaluation and Research at FDA, to the audience at an FDA Town Hall session at BIO 2018, they can concentrate more resources on making a better drug.

	Industry-wide cooperative efforts, however, are difficult to accomplish. Overworked bio/pharma professionals cannot spare time, and drug companies do not want to invest financial resources in consortiums or efforts that cannot demonstrate bottom-line results. Perhaps the greatest hurdle to cooperation is the resistance to share information about internal business or technical operations outside of the company.

	As an independent channel for information and insight about pharmaceutical formulation, development, and manufacturing, 

 stands ready to publish and share the latest advances, technologies, and processes for bio/pharmaceutical development. We need, however, input from experts working in bio/pharma.

	Although 2019 is four months away, for the publishing world, the new year is right around the corner. The editorial calendar, a list of topics that 

 will cover each month, is complete, and the editors are seeking contributions. Now is a good time to remind bio/pharma experts of ways they can contribute.

	Peer-review papers provide science and technical insight into drug formulation and manufacturing processes including method development, materials analysis, validation studies, equipment testing, and regulatory process analysis. Four types of peer-review submissions are considered: standard data-driven, novel research papers; technical case studies/application notes; topical literature or patent reviews; and science-based opinion papers.

	The double-blind review period typically takes four to six weeks. Accepted papers are scheduled for publication on a first-accepted basis and usually are published four to six months following acceptance.

 editors welcome contributions from experts at bio/pharmaceutical companies, regulatory authorities, industry suppliers, and consultants on a range of development, manufacturing, quality, regulatory, analytical, operational, supply chain, and outsourcing topics. Specific topics are listed on the editorial calendar.

	Industry experts can participate by authoring objective, technical articles, or by providing expert commentary for articles authored by the editors. Ideas for contributions should be discussed with the editors in advance. To start the process, contact us about four months prior to publication.

	To keep the contributions focused on advancing bio/pharma development and manufacturing, the editors employ these guidelines:

 does not charge a fee to publish an editorial-driven article; however, all submissions are reviewed and edited by the editorial team; final publication is determined by the editors.

		All submissions must be original and cannot have been published previously in any format-including company literature or website postings or in another language.

		The contributed paper must be objective and cannot promote a company’s products or services.

		Authors are expected to provide suitable references to published third-party literature to support all statements in submitted manuscripts.

		Authors are required to sign a license agreement prior to publication.

	Detailed submission guidelines are listed on 

 link to learn more about authoring a peer-review paper or technical article; review instructions to prepare the document, figures, and tables; and view the editorial calendar for 2019.

	Our theme for the year is Transforming Bio/Pharma Development and Manufacturing. I hope you collaborate with us.

	When referring to this article, please cite it as R. Peters, “Be a Part of the Solution," 

Sharing know-how can help resolve common bio/pharma technical challenges.

Be a Part of the Solution

	While many people headed to summer vacation fun, FDA was busy in July, outlining a reorganization plan, issuing new guidance documents for gene therapy development, establishing a task force to prevent drug shortages, announcing measures to ensure safety in drug compounding and increase consumer access to nonprescription drugs, and indicating the agency would explore more flexible import policies.

	FDA’s Biosimilars Action Plan (1), announced on July 18, 2018, may have the most implications for the market segment. In introducing the plan, FDA Commissioner Scott Gottlieb took innovator biopharmaceutical companies to task for impeding the delivery of biosimilar drugs to market (2). To date, only three of the 11 biosimilar drugs approved by FDA have reached patients, and the lack of competition in the biosimilar space cost US patients more than $4.5 billion in 2017, Gottlieb noted.

	“Sometimes it feels as if we’re seeing the biosimilars version of ‘Groundhog Day,’ with brand drug makers replaying many of the same tactics, and all of us being too susceptible to many of the same misconceptions about biosimilars’ safety and efficacy relative to originator biologics,” Gottlieb said in prepared remarks at the Brookings Institution. “We’re falling into some of the same doubts and policy constraints that were used to deter competition from generics in the years after the Hatch Waxman Act. But we’re not going to play regulatory whack-a-mole with companies trying to unfairly delay or derail the entry of biosimilar competitors. We’re not going to wait a decade or more for robust biosimilar competition to emerge.”

	Delaying tactics may discourage biosimilar sponsors from developing products and reduce public confidence in market-based pricing mechanisms, ultimately hurting innovator companies, Gottlieb said; therefore, FDA’s Biosimilars Action Plan seeks to achieve a balance between innovation and competition. The Plan, part of the Trump Administration’s Blueprint to Lower Drug Prices, focuses on improving the efficiency of the biosimilar and interchangeable product development and approval process; maximizing scientific and regulatory clarity for biosimilar product development; improving understanding of biosimilars among patients, clinicians, and payors; and supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay competition.

	“Effective market competition from biosimilars depends on additional actions from our public and private sector partners to align reimbursement and formulary design to encourage appropriate biosimilar adoption,” Gottlieb said. “Competition requires all of us to shine a light on the anti-competitive impact of tying rebates and bundling biologics with other products to protect biologics’ market share. And it requires us to educate providers and patients about biosimilars, and why people should have confidence in the safety and effectiveness of these FDA-approved products,” he said.

	Prior to the introduction of the Biosimilar Action Plan, the Biotechnology Innovation Organization said-in response to the Blueprint to Lower Drug Prices-that it was working to “increase marketplace competition by speeding regulatory approval of more innovative drugs, and promoting greater and faster generic and biosimilar entry once patents and exclusivities for innovator drugs have expired,” but opposed ideas that “impeded innovation” such as price controls, drug importation, or direct government of negotiation of Medicare drug prices (3).

	While there appears to be general agreement on the end-game, the means of getting there are up for debate. A public hearing scheduled for Sept. 4, 2018 could have some interesting conversations.

	1. FDA, Biosimilars Action Plan: Balancing Innovation and Competition, July 2018.
	2. FDA, Remarks from FDA Commissioner Scott Gottlieb, MD, as prepared for delivery at the Brookings Institution on the release of the FDA’s Biosimilars Action Plan, July 18, 2018.
	3.  Biotechnology Innovation Organization, “BIO Submits Comments Re: HHS Blueprint to Lower Drug Prices and Reduce Out-of-Pocket Costs,” Statement, July 13, 2018.

	When referring to this article, please cite it as R. Peters, “FDA is Not Playing Games with Biosimilars" 

Frustrated by slow market adoption, Gottlieb maps out new plan for biosimilar competition.

FDA is Not Playing Games with Biosimilars

	In introducing FDA’s Biosimilars Action Plan (1) on July 18, 2018 at the Brookings Institution, FDA Commissioner Scott Gottlieb issued strong criticism of the biopharmaceutical industry’s slow delivery of biosimilar drugs to market.

	Through July 2018, only three of the 11 biosimilar drugs approved by FDA have reached patients, and the lack of competition in the biosimilar space cost US patients more than $4.5 billion in 2017, Gottlieb noted in prepared remarks (2). The estimate was a preview of soon-to-be-released FDA analysis of biosimilar competition across Organization for Economic Co-operation and Development (OECD) markets and projections of the impact on the US market if all FDA-approved biosimilars were “successfully marketed here in a timely fashion,” Gottlieb said.

	Biologic-based drugs represent 40% of total spending on prescription drugs, but less than 2% of Americans use them, said Gottlieb. “So, enabling a path to competition for biologics from biosimilars is key to reducing costs and to facilitating more innovation.”

	Litigation, intellectual property, and pricing and rebate strategies have contributed to delays in getting biosimilars to market, similar to tactics employed with the rise of generic small-molecule drugs.

	“Sometimes it feels as if we’re seeing the biosimilars version of ‘Groundhog Day,’ with brand drug makers replaying many of the same tactics, and all of us being too susceptible to many of the same misconceptions about biosimilars’ safety and efficacy relative to originator biologics,” Gottlieb said in prepared remarks. “We’re falling into some of the same doubts and policy constraints that were used to deter competition from generics in the years after the Hatch Waxman Act. But we’re not going to play regulatory whack-a-mole with companies trying to unfairly delay or derail the entry of biosimilar competitors. We’re not going to wait a decade or more for robust biosimilar competition to emerge.”

	Competition strengthens innovator drug efforts

	Delaying tactics may discourage biosimilar sponsors from developing products and reduce public confidence in market-based pricing mechanisms, ultimately hurting innovator companies, Gottlieb said. Therefore, FDA’s Biosimilars Action Plan seeks to achieve a balance between innovation and competition. “Our aim is to reduce the time, uncertainty, and cost of drug development, while also supporting a competitive market through the efficient approval of lower-cost generic, biosimilar, and interchangeable alternatives after the expiration of patents or other statutory exclusivities,” Gottlieb noted.

	FDA’s Biosimilars Action Plan, part of the Trump Administration’s Blueprint to Lower Drug Prices, focuses on the following four areas:

Improving the efficiency of the biosimilar and interchangeable product development and approval process.

 Priorities include development of application review templates for 351(k) biologics license applications; improved coordination and support within FDA through the Office of Therapeutic Biologics and Biosimilars; coordination with the Center for Drug Evaluation and Research; and introduction of information resources and tools to assist biosimilar sponsors, such as an index of critical quality attributes.

Maximizing scientific and regulatory clarity for the biosimilar product development community. 

Priorities include guidance documents for scientific and regulatory predictability, harmonization with international regulations, acceptance of non-US comparator products, and use of real-world data to support regulatory decisions related to biosimilars. To date, FDA has issued six final and four draft guidance documents for biosimilars.

Developing effective communications to improve understanding of biosimilars among patients, clinicians, and payors

. FDA noted the need for audience-appropriate educational materials for patients, clinicians, and payors to inform various groups about biosimilars and the processes FDA uses to evaluate them.

Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay competition. 

FDA said it will clarify its position on issues affecting reference product exclusivity to achieve balance between innovation and competition. The agency also would identify ways statutory or regulatory requirements may delay biosimilar approvals and work with Congress to close any loopholes.

	Gottlieb noted that the current generic-drug market “while not perfect, is robust in most respects. But it took about two decades to develop.” Prescriber and patient confidence in generic drugs had to be developed, legal tactics restricting competition had to be addressed, and coverage systems had to be changed to take advantage of generic entry, he said, and the experience with generic drugs demonstrates that FDA cannot address these issues alone.

	“Effective market competition from biosimilars depends on additional actions from our public and private sector partners to align reimbursement and formulary design to encourage appropriate biosimilar adoption,” Gottlieb said. “Competition requires all of us to shine a light on the anti-competitive impact of tying rebates and bundling biologics with other products to protect biologics’ market share. And it requires us to educate providers and patients about biosimilars, and why people should have confidence in the safety and effectiveness of these FDA-approved products.

	“Without those actions, our collective vision of a pathway for more affordable biosimilar products will be frustrated,” he said.

Biosimilars Action Plan: Balancing Innovation and Competition

Remarks from FDA Commissioner Scott Gottlieb, M.D., as prepared for delivery at the Brookings Institution on the release of the FDA’s Biosimilars Action Plan

In launching FDA’s Biosimilar Action Plan, Gottlieb takes innovator companies to task for delaying competitive biosimilar products.