Explore the vast range of titles available.

This portrait of the global debate over patent law and access to essential medicines focuses on public health concerns about HIV/AIDS, malaria, tuberculosis, the SARS virus, influenza, and diseases of poverty. The essays explore the diplomatic negotiations and disputes in key international fora, such as the World Trade Organization, the World Health Organization and the World Intellectual Property Organization. Drawing upon international trade law, innovation policy, intellectual property law, health law, human rights and philosophy, the authors seek to canvass policy solutions which encourage and reward worthwhile pharmaceutical innovation while ensuring affordable access to advanced medicines. A number of creative policy options are critically assessed, including the development of a Health Impact Fund, prizes for medical innovation, the use of patent pools, open-source drug development and forms of 'creative capitalism'.

After decades of disregard in the Western world, phage therapy is witnessing a return of interest. However, the pharmaceutical legislation that has since been implemented is basically designed for regulating industrially-made pharmaceuticals, devoid of any patient customization and intended for large-scale distribution. Accordingly, the resulting regulatory framework is hardly reconcilable with the concept of sustainable phage therapy, involving tailor-made medicinal products in the global perspective of both evolutionary and personalized medicine. The repeated appeal for a dedicated regulatory framework has not been heard by the European legislature, which, in this matter, features a strong resistance to change despite the precedent of the unhindered implementation of advanced therapy medicinal product (ATMPs) regulation. It is acknowledged that in many aspects, phage therapy medicinal products are quite unconventional pharmaceuticals and likely this lack of conformity to the canonical model hampered the development of a suitable regulatory pathway. However, the regulatory approaches of countries where phage therapy traditions and practice have never been abandoned are now being revisited by some Western countries, opening new avenues for phage therapy regulation. As a next step, supranational and international organizations are urged to take over the initiatives originally launched by national regulatory authorities.

It is now a decade since the World Trade Organization (WTO) adopted the \"Declaration on the TRIPS Agreement and Public Health\" at its 4th Ministerial Conference in Doha. Many anticipated that these actions would lead nations to claim compulsory licenses (CLs) for pharmaceutical products with greater regularity. A CL is the use of a patented innovation that has been licensed by a state without the permission of the patent title holder. Skeptics doubted that many CLs would occur, given political pressure against CL activity and continued health system weakness in poor countries. The subsequent decade has seen little systematic assessment of the Doha Declaration's impact. We assembled a database of all episodes in which a CL was publically entertained or announced by a WTO member state since 1995. Broad searches of CL activity were conducted using media, academic, and legal databases, yielding 34 potential CL episodes in 26 countries. Country- and product-specific searches were used to verify government participation, resulting in a final database of 24 verified CLs in 17 nations. We coded CL episodes in terms of outcome, national income, and disease group over three distinct periods of CL activity. Most CL episodes occurred between 2003 and 2005, involved drugs for HIV/AIDS, and occurred in upper-middle-income countries (UMICs). Aside from HIV/AIDS, few CL episodes involved communicable disease, and none occurred in least-developed or low-income countries. Given skepticism about the Doha Declaration's likely impact, we note the relatively high occurrence of CLs, yet CL activity has diminished markedly since 2006. While UMICs have high CL activity and strong incentives to use CLs compared to other countries, we note considerable countervailing pressures against CL use even in UMICs. We conclude that there is a low probability of continued CL activity. We highlight the need for further systematic evaluation of global health governance actions. Please see later in the article for the Editors' Summary.

Purpose To identify factors associated with success of Market Authorisation Applications (MAAs) for pharmaceutical drugs submitted to the European Medicines Agency (EMEA), with an emphasis on the Scientific Advice (SA) given by the Committee for Human Medicinal Products (CHMP). Methods MAAs with a CHMP decision (outcome) between 1 January 2004 and 31 December 2007 were included in the analysis. Factors evaluated were: company size, orphan drug (OD) status, product type, existence of SA, compliance with SA, therapeutic area and year of outcome. Compliance with SA was retrospectively assessed with reference to three critical clinical variables in pivotal studies: choice of primary endpoint, selection of control and statistical methods. Results Of 188 MAAs with an outcome, 137 (72.9%) were approved, whereas 51 (27.1%) were not approved or were withdrawn by the company. In the simple logistic regression analysis, company size [odds ratio (OR) 2.96, 95% confidence interval (CI) 1.92; 4.56, p < 0.0001) was positively correlated with a positive outcome, whereas OD status (OD vs. non-OD: OR 0.38, 95% CI 0.19; 0.77, p = 0.0067) was negatively correlated. A total of 59 (31.4%) MAAs had obtained SA related to one or more of the three critical variables. Thirty-nine of these were assessed as being compliant with SA. Obtaining an SA per se was not associated with outcome (SA vs. no-SA: OR 0.96, 95% CI 0.49; 1.88, p = 0.92), but complying with SA was significantly associated with positive outcome (compliant with SA vs. no-SA: OR 14.71, 95% CI 1.95; 111.2; non-compliant with SA vs. no-SA: OR 0.17, 95% CI 0.06; 0.47, p < 0.0001). Stepwise regression analysis revealed that company size and SA compliance were independent predictors of outcome. The proportion of the MAAs that had received SA increased from 22% in 2004 to 47% in 2007. Company size and product type were associated with the frequency of requesting SA (26, 33 and 46% for small, medium-sized and large companies, respectively; 16, 39 and 48% for known chemical substances, new chemical substances and biologics, respectively). Factors related to compliance with SA were company size and OD status (25, 60 and 84% for small, medium-sized, and large companies, respectively; 77 and 38% for non-OD and OD status, respectively). Conclusions The strong association between company size and outcome suggests that resources and experience in drug development and obtaining regulatory approval are critical factors for a successful MAA. In addition, obtaining and complying with SA appears to be a predictor of outcome. Based on this analysis, companies, particularly smaller ones and those developing orphan drugs, are recommended to engage in a dialogue with European regulators via the SA procedure. Obtaining SA early in development and at major transition points as well as compliance with the advice given by the CHMP are recommended.

Objectives. We sought to collect and characterize all laws governing the operation of prescription monitoring programs (PMPs), state-level databases that collect patient-specific prescription information, which have been suggested as a tool for reducing prescription drug overdose fatalities. Methods. We utilized a structured legal research protocol to systematically identify, review, and code all PMP statutes and regulations effective from 1998 through 2011. These laws were then abstracted along eleven domains, including reporting provisions, data sharing, and data access. Results. PMP characteristics vary greatly among states and across time. We observed an increase in the types and frequency of data required to be reported, the types of individuals permitted to access PMP data, and the percentage of PMPs authorized to proactively identify outlier prescribers and patients. As of 2011, 10 states required PMPs to report suspicious activity to law enforcement, while only 3 required reporting to the patient’s physician. None required linkage to drug treatment or required all prescribers to review PMP data before prescribing. Few explicitly address data retention. Conclusions. State PMP laws are heterogeneous and evolving. Future studies of PMP effectiveness should take these variations into account.

In March 2017, the US FDA introduced the new Regenerative Medicine Advanced Therapy (RMAT) designation thus recognizing the enormous potential of these medicines and the need for efficient regulatory tools to accelerate their development and their commercial availability. The development of regenerative medicines is very challenging because of their complex and unique nature, especially to the rather unexperienced small- and medium-sized developing enterprises. With the new RMAT designation, FDA aims at providing intensive support to companies developing cell- and tissue-based therapies, tissue-engineering products, and combination treatments. This may also include cell-based products where the genome has been edited by emerging technologies such as CRISPR-Cas9. This article presents the newly launched “Regenerative Medicine Advanced Therapy” (RMAT) designation, outlines existing FDA regulatory tools aiming at expediting approval, and discusses the overall value of these programs. Additionally, recommendations are provided for companies developing these very specific and complex therapies on how and when to consider these tools for an integrated development and regulatory strategy.

This study evaluated the effect of the patent linkage system, fully introduced by the Korea-U.S. Free Trade Agreement in 2015, on patent challenges and the effective market exclusivity of new medicines in Korea. We used pharmaceutical approval data and pharmaceutical litigation data to detect new medicines and their counterparts, to collect patent challenges against new medicines, and to calculate effective market exclusivity for new medicines. Then, a nonparametric event history model was applied to statistically explain the duration of the market exclusivity of new medicines. Between 2007 and 2011, a total of 94 new medicines, consisting of 82 new chemical entities and 12 new biologics, were approved. The patent linkage system encouraged patent litigations to occur sooner, with a race to challenge the patents by various generic applicants. However, it was difficult to conclude that patent challenges had a significant impact on the prolongation of effective market exclusivity. The patent linkage system had a neutral effect on the effective market exclusivity of new medicines and encouraged patent challenges without abbreviating effective market exclusivity. In addition, this study highlights an important issue regarding biologics that has not been the subject of market competition, even for patent challenges.

Aimed at smaller companies and academic researchers, PRIME (PRIority MEdicines) aims to streamline the development process by offering early advice on clinical trial design. The EMA has not backtracked and at a press conference to launch PRIME, Zaide Frias, head of regulatory affairs for the agency, said that small and medium sized companies needed more assistance.