Patricia Van Arnum was executive editor of Pharmaceutical Technology.

Patricia Van Arnum

The Pharmaceutical Manufacturers of America (PhRMA) and the Biotechnology Industry Organization (BIO) are among 16 business groups that have joined a newly formed coalition, the Alliance for Fair Trade with India (AFTI). The AFTI, which is cochaired by the National Association of Manufacturers  (NAM) and the US Chamber of Commerce’s Global Intellectual Property Center, was formed to support increased action to resolve what it terms as "discriminatory" trade practices, including what it terms as an "erosion" of intellectual property (IP) rights in India. 

“India’s recent discriminatory and unfair actions are harming American jobs and have put at risk the $60-billion trade relationship we have with our fourth largest trading partner,” said NAM President and CEO Jay Timmons, in a June 18, 2013 NAM  

 “We are asking the Obama Administration to engage India’s government at the highest levels to put an end to these harmful practices and to prevent this from happening again. The NAM is committed to working with our industry partners to ensure that India abides by global trade rules to protect America’s competitiveness.” 

Earlier this month, the NAM, along with other industry associations, including PhRMA and BIO, sent a 

to President Obama raising concerns about India’s trade practices and their impact on US-based manufacturers. “It is time the Government of India ended discrimination against our nation’s exporters and took steps to ensure it is not repeated in the future,” the letter noted. “To achieve this result, we urge the US government immediately to initiate bilateral engagement at the highest levels and to coordinate closely with the European Union and other like-minded economies.” 

In the coming weeks, AFTI said it will work with the Administration and members of Congress to pursue public policy-options that “help create a level playing field for US exporters operating in India,” according to June 18, 2013 AFTI 

  “Additionally, AFTI will outline the consequences of inaction, specifically as they relate to job creation, economic growth and continued innovation” said the release. 

In addition to AFTI, more than 170 members of the US House of Representatives and 40 US senators sent letters to President Obama and US Secretary of State John Kerry expressing concerns with India’s “discriminatory” trade and intellectual property practices and urged for immediate action to address them.  On June 14, Senate Finance Committee Chairman Max Baucus (D-MT) and Ranking Member Orrin Hatch (R-UT) sent a 

letter, and on June 18, more than 170 House members, led by Reps. Erik Paulsen (R-MN) and John Larson (D-CT) sent one.

 On June 20, House Ways and Means Committee Chairman Dave Camp (R-MI), Ranking Member Sander Levin (D-MI), Trade Subcommittee Chairman Devin Nunes (R-CA), Trade Subcommittee Ranking Member Charles Rangel (D-NY) and 35 members of the House Ways and Means Committee also sent a 

 On June 20, 40 senators, led by Sens. Rob Portman (R-OH) and Bob Menendez (D-NJ) also sent a 

The letters come as Secretary Kerry traveled to the Middle East and Asia, which included a trip to New Delhi, from June 23-25, where he chaired the interagency delegation to the fourth annual US–India Strategic Dialogue. The Strategic Dialogue, inaugurated in 2009, is a forum for discussing US–India cooperation on bilateral and regional issues 

Articles

The Alliance for Fair Trade with India is seeking action to resolve discriminatory trade practices and improved protection of intellectual property rights.

PhRMA, BIO Join Newly Formed Coalition Advocating for Fair Trade with India

on June 14, 2013, that it is proceeding with a formal sale process of the company and will invite Royalty Pharma, who had 

an earlier $8-billion unsolicited takeover bid for the company to participate if Royalty Pharma wishes. On June 17, Elan shareholders voted in favor of a proposal to buy back $200 million in shares using the proceeds of Elan's sale of its share of multiple-sclerosis drug Tysabri (natalizumab). In response, Royalty Pharma 

 its request for a judicial review of the Irish Takeover Panel’s decision requiring it to lapse its offer if Elan shareholders approved the share-repurchase program.

Although Elan shareholders approved the share repurchase at the company’s extraordinary general meeting held on June 17, they voted down three other transactions: a $1-billion deal with the US pharmaceutical company Theravance that was announced in May 2013; a proposed EUR-263.5 million ($350-million) acquisition of AOP Orphan Pharmaceuticals, a Vienna-based pharmaceutical company focused on rare and orphan diseases; and the divesture of Elan’s ELND005, a drug in clinical development for treating separate indications of Alzheimer's disease and bipolar disease to Speranza Therapeutics. In the proposed Theravance deal, Elan would have paid $1 billion in a royalty-participation agreement in which Elan would receive a 21% stake in potential future royalty payments related to four respiratory programs in which Theravance is partnered with GlaxoSmithKline. 

The move follows rejection of Elan shareholders of certain key deals and withdrawal of Royalty Pharma bid.

Elan Initiates Formal Sale Process of Company

 Quality is of utmost importance in drug development and manufacturing. The increased globalization of the pharmaceutical and biopharmaceutical industries, resulting in more complex and elongated supply chains on a raw material and ingredients basis, obligates suppliers and pharmaceutical and biopharmaceutical companies to develop ways to achieve greater transparency and understanding of those supply chains to ensure product quality and regulatory compliance. 

 will examine these issues in a educational 

Achieving Raw-Material Transparency in the Pharmaceutical/ Biopharmaceutical Supply Chain

, live on Tuesday June 18 from 11:00 AM to 12:00 PM EST. This 60-minute webcast will examine industry practice and the use of regulatory guidance (FDA, EU, and ICH) for developing operational control and quality processes for mitigating risk in the pharmaceutical/biopharmaceutical supply chain. Industry experts will share ways, from both a supplier and pharmaceutical/biopharmaceutical company perspective, on ways to resolve the challenges toward achieving supply-chain transparency and its management. The webcast will feature supplier and customer strategies and a systems approach for the supply-chain transparency of critical raw materials supplied for use in regulated applications.

				The panelists for the webcast include: Wes Schmidt, Divisional Vice-President of AbbVie Operations Quality Assurance; Tom Beil, Vice-President of Quality and Regulatory Affairs, Sigma-Aldrich/SAFC; and Daniel Matlis, president of Axendia. The panelists will share insight into identifying what is critical to gain supply-chain transparency for raw materials; understanding challenges in risk mitigation; and learning how to identify critical requirements when seeking to balance between cost and security as a drug moves through the pipeline from research to commercialization.

				Audience members will be able to ask the panelists questions for additional insight during the live webcast on Tuesday June 18 from 11:00 AM to 12:00 PM EST. Additional information on the webcast, including how to register for the live event and on-demand viewing may be found

Quality is of utmost importance in drug development and manufacturing.

Quality Focus: Ensuring Raw Material Transparency

Risk and reward. It is a balance that has to be achieved in any business endeavor and is of utmost importance for pharmaceutical and biopharmaceutical companies managing their growth and manufacturing in emerging markets. Emerging markets are a crucial part of pharmaceutical companies’ growth strategies, but in serving those markets, pharmaceutical and biopharmaceutical manufacturers must align that strategy with partners that can facilitate access to local markets, manage complex supply chains, meet global and national regulatory standards for quality, and secure production for local as well as established markets in North America and Western Europe.

 will examine these issue in greater depth in an educational live 

Risk-Mitigation Strategies for API Manufacturing in Emerging Markets

 on Wednesday June 19 11:00 AM to 12:00 PM EST. This 60-minute webcast will provide insight and case-study analysis on the approaches taken by pharmaceutical companies to build their manufacturing networks in select emerging markets while mitigating risk in supplier selection and qualification to ensure reliable and consistent product supply.

		Panelists for the webcast include Thomas Niemeyer, Global External Supply Lead, Chemical Research & Development, Pfizer; Andy Wong, Principal, IMS Consulting Group; and Thomas Speace, President, Neuland Laboratories. The panelists will share insight into the opportunities in emerging markets; how to apply risk-mitigation strategies for supplier selection and qualification; how to manage supply chains for intermediates and APIs; and elucidate the regulatory and unique national requirements in emerging markets for pharmaceutical manufacturing.

		Audience members will be able to ask the panelists questions for additional insight during the live 

 on Wednesday June 19 from 11:00 AM to 12:00 PM EST. Additional information and how to register for the live webcast and on-demand viewing may be found 

Risk and reward. It is a balance that has to be achieved in any business endeavor and is of utmost importance for pharmaceutical and biopharmaceutical companies managing their growth and manufacturing in emerging markets.

Risk-Mitigation Strategies in Drug Manufacturing for Emerging Markets

The board of directors and executive management of the pharmaceutical company Elan have rejected a revised bid of $15.50 a share or approximately $8 billion by the pharmaceutical company Royalty Pharma. In turning down the bid, Elan says the offer undervalues the company and has urged Elan shareholders to reject the bid in a shareholder meeting to be held on June 17, 2013. 

Royalty Pharma made an unsolicited revised bid to acquire all the shares of Elan for $13.00 per share plus up to an additional $2.50 per share in contingent value rights for a total bid price of $15.50 a share. In rejecting the bid, Elan said in a June 11, 2013 

 the offer was “wholly inadequate for Elan shareholders,” and in a letter to its shareholders, urged them to reject the offer at an upcoming extraordinary general meeting to be held on June 17.  A key point of contention is the valuation of Elan’s participation in the multiple-sclerosis drug Tysabri (natalizumab). Earlier this year, Elan restructured its collaboration with Biogen Idec for Tysabri, in which Elan received a $3.25-billion payment plus an ongoing royalty interest in the drug. Elan says that the royalty and cash alone value Tysabri to be worth at least $15.50 per share or as much as $20.80 per share, thereby undervaluing Elan by as much as $4.3 billion. 

In addition to voting on the Royalty Pharma offer, Elan shareholders will also be voting on whether to approve three earlier deals of Elan: a $1-billion deal with the US pharmaceutical company Theravance that was announced in May 2013; a proposed EUR-263.5 million ($350-million) acquisition of AOP Orphan Pharmaceuticals, a Vienna-based pharmaceutical company focused on rare and orphan diseases; and the divesture of Elan’s ELND005, a drug in clinical development for treating separate indications of Alzheimer's disease and bipolar disease to Speranza Therapeutics. In the Theravance deal, Elan would pay $1 billion in a royalty-participation agreement in which Elan would receive a 21% stake in potential future royalty payments related to four respiratory programs in which Theravance is partnered with GlaxoSmithKline. 

Elan’s board and executive management said it is “exploring all opportunities that maximize the full value of the company for its shareholders” and that it will consider other offers for the company. 

to say that subsequent deals by Elan, including the deals involving Theravance, AOP, and Speranza, as well as share repurchase transactions “do not come close to replacing the earnings that Elan gave up by selling half of its Tysabri interest,” and urged Elan shareholders to vote against the resolutions at the upcoming shareholders’ meeting. 

Elan urges its shareholders to reject bid in an upcoming meeting on June 17.

Elan Board Rejects Multibillion Takeover Bid from Royalty Pharma

 to Novartis for cGMP violations at its manufacturing facility for finished pharmaceuticals in Unterach, Austria. The site became part of Sandoz and Novartis through the acquisition of EBEWE Pharma in 2009.

	The Warning Letter was issued based on an inspection of the facility from Oct. 15–23, 2012 at which FDA noted several violations of cGMP in the company’s quality control unit. FDA cited the company for failing to obtain FDA’s approval of changes in the quality controls established in an approved application prior to distributing a product with those changes. The agency noted that the company manufactured and distributed finished parenteral drugs to the US market using unapproved procedures for visual inspection prior to obtaining approval of a supplement regarding these changes.

	FDA said it informed Novartis several times, in writing and orally, not to distribute the implicated product until receiving approvals of the supplements and had informed the company in writing on March 14, 2012, that these supplements were not approvable. Although Novartis ceased using the unapproved method, FDA said that the company failed to provide a plan to address the products distributed in the US market that used the method.

	FDA is asking Novartis to provide all the distribution information of the lots manufactured using these unapproved methods, including risk assessments if the drug were to remain on the market. The agency is also asking the company to provide a complete list of products it manufactures and a commitment to audit current production procedures against the standards established in approved applications (including approved supplements). It is also asking the company to provide an action plan to appropriately address each discrepancy identified by the audit and to describe the specific corrective actions the firm is implementing to ensure adherence to application commitments in the future as well as proper evaluation and handling of proposed changes to them.

	FDA also cited Novartis for failing to establish a scientifically sound and appropriate test procedure to determine conformance of the finished drug product to an established specification. The agency said “the procedures established to perform the visual inspection of critical defects, such as particulate matter in finished parenteral drug vials, are inadequate in that operators following these procedures have repeatedly failed to detect visible particles.” The agency said that on at least 10 occasions, the company’s inspection of finished-product vials failed to detect visible particle material. “Although we recognize that in some instances your firm rejected batches with these defects, we are concerned that you did not detect visible particles until after release of other affected lots,” said FDA in its Warning Letter. “Because your lot inspection failed to detect visible particle matter in numerous instances, we are concerned that your inspection program is not robust enough to serve its intended purpose.”

	FDA is asking Novartis to describe the actions taken to ensure that the finished parenteral drugs the company manufactures are essentially free of particle matter. The agency also is asking the company to describe its revised inspection program and enhanced acceptance-quality-limit program and to indicate the impact of the particle defects on product produced for the US market.

	“We take seriously the warning letter observations cited by the FDA and will work closely and expeditiously to address these concerns to the agency’s full satisfaction,” said Ameet Mallik, Sandoz’ Head of Biopharmaceuticals & Oncology Injectables, in a June 4, 2013 Novartis press release. “Sandoz has made strong progress in strengthening operations in Unterach through significant investments in both resources and state-of-the-art technologies. We remain deeply committed to fully addressing all outstanding issues and meeting all quality standards.”

	Sandoz said since 2011, it is not aware of any adverse events in products manufactured at the Unterach site associated with the observations in the letter. Also, the company does not anticipate any related product supply issues at this time.

 on May 20, 2013, Sandoz was conducting a voluntary nationwide recall to the hospital/user level of two lots of its methotrexate sodium, USP, 25 mg/mL, 40 mL vial injectable product in the US due to the discovery of particulate matter in vials during routine quality examination of retention samples at the manufacturer. The lot numbers and expiration dates of the two recalled lots are: CL0996 (expiration date 12/2013) and CJ4948 (expiration date 05/2013). These lots were distributed nationally across the US and to a single foreign country (Poland).

The company is cited for using unapproved visual-inspection methods for finished parenteral drugs and conducting inadequate visual inspections.