“So we arrive at the million-dollar question: Are regulatory agencies and pharmacopeias doing a good enough job, if a sponsor can comply with [most] regulations and yet send a product on the market which contains carcinogens,” asks Anders Fuglsang, founder of Fuglsang Pharma. “We can’t test for everything, but I’m not entirely happy with that statement as a patient or consumer,” he says. Fuglsang hopes that there will be an independent analysis of the root cause of the nitrosamine contamination, performed by independent experts outside of regulatory agencies or pharmacopeias. In the end, he says, “we can only find what we are looking for.” But the sartan API contamination case suggests a need to focus more closely on assessing potential risks during process synthesis review.

        In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for biopharmaceutical companies, which have experienced significant stock price volatility in recent years. The results of any legal proceedings are inherently uncertain and, regardless of the ultimate outcome or the merits, require substantial time and other resources to defend. Accordingly, any litigation that we could face may result in substantial costs to us, divert management’s attention and resources from our company as well as harm our reputation with analysts and investors, which could substantially harm our business, financial condition and results of operations.

The Medicare Modernization Act imposed new requirements for the distribution and pricing of prescription drugs for Medicare beneficiaries under Part D. Under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities that provide coverage of outpatient prescription drugs. Part D prescription drug plan sponsors are not required to pay for all covered Part D drugs, and each drug plan can develop its own drug formulary that identifies which drugs it will cover and at what tier or level. However, Part D prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all the drugs in each category or class. The Centers for Medicare & Medicaid Services published a final rule in 2014 implementing the Medicare Modernization Act. Contrary to the proposed rule, which would have enabled Part D plans to offer fewer drugs, the final rule maintained the existing six protected classes of drug categories, but stated that some of the proposals not included in the final rule could still be finalized in the future, which would impact payor formulary and coverage decisions.

Chen, C. Z., Li, L., Lodish, H. F. & Bartel, D. P. MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83–86 (2004).

If a Non-Electing U.S. Holder who is an individual dies while owning our ordinary shares, the Non-Electing U.S. Holder’s successor would be ineligible to receive a step-up in tax basis of such ordinary shares. Non-Electing U.S. Holders should consult their tax advisors regarding the application of the “net investment income tax” (described below) to their specific situation.

        In order to secure coverage and reimbursement for any product approved for sale, a company may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the costs required to obtain FDA or other comparable regulatory approvals. Nonetheless, product candidates may not be considered medically necessary or cost effective. Additionally, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a drug product does not assure that other payors will also provide coverage for the drug product. Third-party reimbursement may not be sufficient to maintain price levels high enough to realize an appropriate return on investment in product development.

EpiCept Corporation (NasdaqCM:EPCT) is focused on the development and commercialization of pharmaceutical products for the treatment of cancer and pain. The Company’s lead product is Ceplene®, which has been granted full marketing authorization by the European Commission for the remission maintenance and prevention of relapse in adult patients with Acute Myeloid Leukemia (AML) in first remission. The Company has two oncology drug candidates currently in clinical development that were discovered using in-house technology and have been shown to act as vascular disruption agents in a variety of solid tumors. The Company’s pain portfolio includes EpiCept™ NP-1, a prescription topical analgesic cream in late-stage clinical development designed to provide effective long-term relief of pain associated with peripheral neuropathies.

A brain is a network of neurons i.e. a neural network (a single neuron is also a network and so on). The immune system is also a network. In general, a system can be considered a network.A living organism is a network. When dies the network dissolves in smaller networks.

Wu, C. C. et al. The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte. J Mol Cell Cardiol 27, 1263–9 (1995).

        The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional application which matures into a granted patent. A U.S. patent also may be accorded a patent term adjustment, or PTA, under certain circumstances to compensate for delays in obtaining the patent caused by the U.S. Patent and Trademark Office. In some instances, such a PTA may result in a U.S. patent term extending beyond 20 years from the earliest date of filing a non-provisional patent application. In addition, in the U.S., the term of a U.S. patent that covers an

FDA approval could be more complicated because they need to target one disease in particular though, and they would probably need to focus on a very serious disease to justify gene therapy.

1. P. Johnson, “Quality In, Quality Out:Regulatory Drivers of Supplier Quality Management in the Pharm and Biopharma Industries,” Xtalks Webcast (September 18, 2018). 2. FDA, “Valsartan Products Under Recall,” fda.gov, August 28, 2018. 3. P. Magee and J. Barnes, “British Journal of Cancer , 10 (1) 114-122 (1956), 4. C. Purdy, “A Common Blood Pressure Medicine is Being Recalled Because it Was Mixed With NDMA". 5. A. Tricker et al, Carcinogenesis 12(2); 257-261 (1991). 6. M. Jagerstad, Mutation Research 574(1-2), 156-172 (August 2005) 7. EMA, “Valsartan: Review of Impurities Extended to Other Sartan Medicines,” Press Release, September 21, 2018. 8. FDA, “FDA Announces Preliminary GC/MS Headspace Method for Determining NDMA in valsartan” Press Release, August, 2018. 9. EDQM, “OMCLs Release Three Methods for Determination of NDMA in Sartans,” Press Release, September 21, 2018. 10. FDA Press Release, “FDA Places Zhejiang-Huahai on Import Alert,” fda.gov , September 28, 2018. 11. EMA, Press Release, “EU Inspection Finds Zhejiang Huahai Site Non-Compliant,” ema.europa.eu , September 28, 2018. 12. FDA, Form 483, fda.gov