On July 6, 2018, the European Medicines Agency recalled certain batches of valsartan and valsartan/HCT film-coated tablets distributed in 22 countries in Europe, plus Canada.[14] Zhejiang Huahai Pharmaceutical Co. (ZHP) in Linhai, China manufactured the bulk ingredient contaminated by N-nitrosodimethylamine (NDMA), a carcinogen. The active pharmaceutical ingredient was subsequently imported by a number of generic drugmakers, including Novartis, and marketed in Europe and Asia under their subsidiary Sandoz labeling, and in the UK by Dexcel Pharma Ltd and Accord Healthcare.[14] In Canada, the recall involves five companies and a class action suit has been initiated by a private law firm.[15][16] Authorities believe the degree of contamination is negligible, and advise those taking the drug to consult a doctor and not to cease taking the medication abruptly. On July 12, 2018, The National Agency of Drug and Food Control (NA-DFC or Badan POM Indonesia) announced voluntary recalls for two products containing valsartan produced by Actavis Indonesia and Dipa Pharmalab Intersains.[17] On July 13, 2018, the FDA announced voluntary recalls of certain supplies of valsartan and valsartan/hydrochlorothiazide (HCTZ) in the U.S. distributed by Solco Healthcare LLC, Major Pharmaceuticals, and Teva Pharmaceutical Industries.[18] Hong Kong’s Department of Health initiated a similar recall.[19] On August 2, 2018, the FDA published two lengthy, updated lists, classifying hundreds of specific U.S. products containing valsartan into those included versus excluded from the recall.[20] A week later, the FDA cited two more drugmakers, Zhejiang Tianyu Pharmaceuticals of China and Hetero Labs Limited of India, as additional sources of the contaminated valsartan ingredient.[21]

Observation of the mRNA expression levels of the osteogenic markers helps to distinguish the stages of differentiation and maturation of BMSCs into osteoblasts. Previous studies48,49 have shown that ALP is secreted during the early stage of osteogenic differentiation, whereas OCN, a marker of a mature osteoblast differentiation, is a necessary factor for bone calcification and mineralization. BSP is one of the major non-collagenous glycosylated phosphoproteins of the extracellular matrix in bone. It is a mineralized tissue-specific protein that is expressed in differentiated osteoblasts and appears to function in the initial mineralization of bone. In this study, expression of bone-related genes, including Runx-2, ALP, OCN and BSP, is observed to be upregulated in the PArN-BMSCs cultures after 3 days but in the PAr-BMSCs, all the gene expressions are not significantly changed compared to the blank (Fig. 4c). By monitoring the Runx-2 and OCN protein levels, the BMSCs are collected from PE, Par, and PArN at day 7. It is the matrix maturation stage of osteogenic differentiation and the ECM and stem cell functions are kept in balance. Our results (Fig. 4d) confirm that the charged surface (PArN) with tertiary amines increase bone-related protein products. By considering cell calcification, gene expression, and protein production, the positively-charged tertiary amines on PArN have significant effects on signaling BMSCs to differentiate via the osteogenic pathway, while the C-C and C = C groups on PAr are less effective in osteogenesis despite excellent cell attachment and proliferation. It is consistent with chitosan12,50 and polypeptide51 with amino groups.

Even if we complete our planned clinical trials and believe that the clinical data confirms that Aramchol is both safe and effective for its intended use or uses, obtaining approval of an NDA, or other regulatory approval, is an extensive, lengthy, expensive and uncertain process, and the FDA and other regulatory agencies may delay, limit or deny approval of Aramchol for many reasons, including, without limitation, the fact that:

Our Articles provide that a director may, by written notice to the Company, appoint another person to serve as an alternate director provided that such appointment is approved by a majority of the directors then in office, and that such appointing director may remove such alternate director. Any alternate director shall be entitled to notice of meetings of the Board and of relevant committees and to attend and vote accordingly, except that the alternate has no standing at any meeting at which the appointing director is present or at which the appointing director is not entitled to participate as provided in the Companies Law. A person who is not qualified to be appointed as a director, or a person who already serves as a director or an alternate director, may not be appointed as an alternate director.

Bachem has the experience and the financial resources to meet growing regulatory and GMP demands. We have also submitted dozens of technical packages in support of successful IMPD and IND applications.

Any drug product manufactured or distributed by us pursuant to FDA approvals are subject to continuing regulation by the FDA, including, among other things record-keeping requirements; cGMPs; reporting of adverse experiences with the drug; providing the FDA with updated safety and efficacy information; drug sampling and distribution requirements; notifying the FDA and gaining its approval of specified manufacturing or labeling changes; and complying with FDA promotion and advertising requirements.

Demel, R. A. & De Kruyff, B. The function of sterols in membranes. Biochim Biophys Acta 457, 109–32 (1976).

With the exception of products that are authorized centrally, the competent authorities of the member states are responsible for granting marketing authorizations for medicinal products placed on their national markets. If the applicant for a marketing authorization intends to market the same medicinal product in more than one member state, the applicant may seek an authorization progressively in the community under the mutual recognition or decentralized procedure. Mutual recognition procedure, or MRP is used if the medicinal product has already been authorized in a member state. In this case, the holder of this marketing authorization requests the member state where the authorization has been granted to act as reference member state by preparing an updated assessment report that is then used to facilitate mutual recognition of the existing authorization in the other member states in which approval is sought (the so-called concerned member state(s)). The reference member state must prepare an updated assessment report within 90 days of receipt of a valid application. This report together with the approved Summary of Product Characteristics, the SmPC (which sets out the conditions of use of the product), and a labeling and package leaflet are sent to the concerned member states for their consideration. The concerned member states are required to approve the assessment report, the SmPC and the labeling and package leaflet within 90 days of receipt of these documents. The total procedural time of the MRP is 180 days.

Yes to all, we could list so many, the work of Luther Burbank fascinates me still. And to clarify, I did not mean to point out Einstein’s humanness, as all great scientists will take a blind path at some point. I was only was using it as an example to refer back to the post about never revisiting the idea of God because there is nothing “factual”. Do we know what we think we know? It quickly become philosophical as I think Paul mentioned.

        Various laws, regulations and executive orders also restrict the use and dissemination outside of the U.S., or the sharing with certain non-U.S. nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products. If we expand our presence outside of the U.S., it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us from developing, manufacturing, or selling certain products and product candidates outside of the U.S., which could limit our growth potential and increase our development costs.

        In May 2018, we entered into a sales agreement (the "Sales Agreement") with Stifel, Nicolaus & Company, Incorporated ("Stifel"), which permitted us to sell, from time to time, at our option, up to an aggregate of $50.0 million of shares of our common stock through Stifel, as sales agent. In December 2018, we terminated the Sales Agreement. Prior to termination, we had not sold any Shares pursuant to the Sales Agreement.

        In February 2018, we announced the completion of dosing and top-line data for our global Phase 2 clinical program in PNH. The global, dose-finding, twelve-week, open-label Phase 2 program was designed to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and pharmacodynamics of zilucoplan in patients with PNH.