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Knoss W.,Federal Institute for Drugs and Medical Devices | Chinou I.,National and Kapodistrian University of Athens
Planta Medica | Year: 2012

The European legislation on medicinal products also addresses the medicinal use of products originating from plants. The objective of the legislation is to ensure the future existence of such products and to consider particular characteristics when assessing quality, efficacy, and safety. Two categories are defined: i) herbal medicinal products can be granted a marketing authorisation; and ii) traditional herbal medicinal products can be granted a registration based on their longstanding use if they are complying with a set of provisions ensuring their safe use. The Committee on Herbal Medicinal Products (HMPC) was established at the European Medicines Agency (EMA) to provide monographs and list entries on herbal substances and preparations thereof. Meanwhile, approx. 100 monographs have been published, which define a current scientific and regulatory standard for efficacy and safety of herbal substances and herbal preparations used in medicinal products. This harmonised European standard will facilitate the availability and adequate use of traditional herbal medicinal products and herbal medicinal products within the European Union. Consequent labelling shall also enable patients and health care professionals to differentiate medicinal products from other product categories like cosmetics, food supplements, and medical devices. Copyright © 2012 by Thieme Medical Publishers, Inc.


SAINT-LAURENT, CANADA--(Marketwired - Dec. 14, 2016) - IntelGenx Corp., (TSX VENTURE:IGX)(OTCQX:IGXT), and RedHill Biopharma Ltd. (NASDAQ:RDHL)(TASE:RDHL), today announced the signing of an exclusive license agreement with Pharmatronic Co. ("Pharmatronic Co.") for the commercialization of RIZAPORT® in the Republic of Korea (South Korea). RIZAPORT® is a proprietary oral thin film formulation of rizatriptan for the treatment of acute migraines. Under the terms of the agreement, RedHill granted Pharmatronic Co. the exclusive rights to register and commercialize RIZAPORT® in South Korea. IntelGenx and RedHill are entitled to receive an upfront payment and will be eligible to receive additional milestone payments upon achievement of certain predefined regulatory and commercial targets, as well as tiered royalties. Further financial terms of the agreement were not disclosed. The initial term of the definitive agreement with Pharmatronic Co. is for ten years from the date of first commercial sale and shall automatically renew for an additional two-year term. Commercial launch in South Korea is estimated to take place in the first quarter of 2019. "We are most pleased to be entering the Asian market for the first time with Pharmatronic, a Korean organization committed to customer service excellence," said Dr. Horst G. Zerbe, President and CEO of IntelGenx. "We will be working hard with our partners RedHill and Pharmatronic to bring our innovative product to market for patients in South Korea suffering with migraines. The execution of two commercialization agreements for RIZAPORT® in less than six months demonstrates our relentless execution of strategy to bring our innovative products to the global market." Mr. Adi Frish, RedHill's Senior VP Business Development & Licensing, said: "We are pleased to enter into our second commercialization agreement for RIZAPORT® and look forward to building a long-term relationship with Pharmatronic Co. This agreement for South Korea follows our recent commercialization agreement with Grupo JUSTE S.A.Q.F for Spain. We continue working diligently together with our partner IntelGenx to bring this unique migraine drug to additional markets and expect to re-submit the RIZAPORT® NDA to the FDA in the first half of 2017." RIZAPORT® (5 mg and 10 mg) was granted marketing authorization by the Federal Institute for Drugs and Medical Devices of Germany (BfArM) under the European Decentralized Procedure (DCP), in which Germany served as the Reference Member State for other European Union (EU) countries. This authorization was the first national marketing approval for RIZAPORT®. A first commercialization agreement was signed with Grupo JUSTE S.A.Q.F (Grupo JUSTE) for Spain and additional potential territories and, subsequently, a national Marketing Authorization Application (MAA) for RIZAPORT® was submitted by Grupo JUSTE in Spain under the European DCP. IntelGenx and RedHill expect to re-submit the RIZAPORT® New Drug Application (NDA) to the FDA in the first half of 2017 and subsequently receive a new PDUFA (Prescription Drug User Fee Act) date and are currently in discussions with potential commercialization partners for the U.S. market. RIZAPORT® is a proprietary oral thin film formulation of rizatriptan benzoate, a 5-HT1 receptor agonist and the active drug in Merck & Co.'s Maxalt®. RIZAPORT® 5 mg and 10 mg were approved for marketing in Germany in October 2015 under the European Decentralized Procedure. A New Drug Application for RIZAPORT® was also filed with the U.S. FDA in 2013 and a CRL was received in 2014. RedHill has entered into licensing agreements to commercialize RIZAPORT® in Spain (with Grupo JUSTE S.A.Q.F) and in South Korea (with Pharmatronic Co.). Rizatriptan is considered to be one of the most effective oral triptans, a class of molecules that constricts blood vessels in the brain to relieve swelling and other migraine symptoms. The worldwide annual sales of triptans were estimated to have exceeded $690 million in 2015(1). RIZAPORT® is based on IntelGenx's proprietary VersaFilm™ technology. It dissolves rapidly and releases its active ingredient in the mouth, leading to efficient absorption of the drug through the gastrointestinal tract. The administration method of the RIZAPORT® oral thin film, which does not require the patient to swallow a pill or consume water, along with its pleasant flavor, presents a potentially attractive therapeutic alternative for migraine patients, specifically for patients who suffer from migraine-related nausea, estimated to be approximately 80% of the total migraine patient population(2) and patients suffering from dysphagia (difficulty swallowing). RedHill Biopharma Ltd. (NASDAQ:RDHL)(TASE:RDHL) is a biopharmaceutical company headquartered in Israel, primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill's pipeline of proprietary products includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study and an ongoing proof-of-concept Phase IIa study for multiple sclerosis; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA™ (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered uPA inhibitor, targeting gastrointestinal and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in Germany in October 2015. Pharmatronic Co. is a privately held pharmaceutical company headquartered in Seoul, South Korea which distributes exclusively licensed pharmaceutical products with innovative sales and marketing know-how. Since its establishment in 2005, Pharmatronic Co. has focused R&D and marketing resources on the specialized target field of neurology, ENT and urology, building a strong image as a leading provider in the pharmaceutical and healthcare industry. IntelGenx is a leading oral drug delivery company primarily focused on the development and manufacturing of innovative pharmaceutical oral films based on its proprietary VersaFilm™ technology platform. Established in 2003, the Montreal-based company is listed on the TSX-V and OTC-QX. IntelGenx highly skilled team provides comprehensive pharmaceuticals services to pharmaceutical partners, including R&D, analytical method development, clinical monitoring, IP and regulatory services. IntelGenx state-of-the art manufacturing facility, established for the VersaFilm™ technology platform, supports lab-scale to pilot and commercial-scale production, offering full service capabilities to our clients. More information is available about the company at: www.intelgenx.com. This document may contain forward-looking information about IntelGenx' operating results and business prospects that involve substantial risks and uncertainties. Statements that are not purely historical are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. These statements include, but are not limited to, statements about IntelGenx' plans, objectives, expectations, strategies, intentions or other characterizations of future events or circumstances and are generally identified by the words "may," "expects," "anticipates," "intends," "plans," "believes," "seeks," "estimates," "could," "would," and similar expressions. All forward looking statements are expressly qualified in their entirety by this cautionary statement. Because these forward-looking statements are subject to a number of risks and uncertainties, IntelGenx' actual results could differ materially from those expressed or implied by these forward looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed under the heading "Risk Factors" in IntelGenx' annual report on Form 10-K, filed with the United States Securities and Exchange Commission and available at www.sec.gov, and also filed with Canadian securities regulatory authorities and www.sedar.com. IntelGenx assumes no obligation to update any such forward-looking statements. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange), nor the OTCQX accepts responsibility for the adequacy or accuracy of this release. (2) Lipton RB, Buse DC, Saiers J, Fanning KM, Serrano D, Reed ML. (2013) Frequency and burden of headache-related nausea: results from the American Migraine Prevalence and Prevention (AMPP) study, Headache. 2013 Jan;53(1):93-103.


TEL-AVIV, Israel, Dec. 14, 2016 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, together with IntelGenx Corp. (TSX-V:IGX) (OTCQX:IGXT) (“IntelGenx”), a Canadian drug delivery company focused on oral drug delivery, today announced the signing of an exclusive license agreement with Pharmatronic Co. (“Pharmatronic Co.”) for the commercialization of RIZAPORT® in the Republic of Korea (South Korea). RIZAPORT® is a proprietary oral thin film formulation of rizatriptan for the treatment of acute migraines. Under the terms of the agreement, RedHill granted Pharmatronic Co. the exclusive rights to register and commercialize RIZAPORT® in South Korea. RedHill and IntelGenx are entitled to receive an upfront payment and will be eligible to receive additional milestone payments upon achievement of certain predefined regulatory and commercial targets, as well as tiered royalties. The initial term of the definitive agreement with Pharmatronic Co. is for ten years from the date of first commercial sale and shall automatically renew for an additional two-year term. Commercial launch in South Korea is estimated to take place in the first quarter of 2019. Mr. Adi Frish, RedHill’s Senior VP Business Development & Licensing, said: “We are pleased to enter into our second commercialization agreement for RIZAPORT® and look forward to building a long-term relationship with Pharmatronic Co. This agreement for South Korea follows our recent commercialization agreement with Grupo JUSTE S.A.Q.F for Spain. We continue working diligently together with our partner IntelGenx to bring this unique migraine drug to additional markets and expect to re-submit the RIZAPORT® NDA to the FDA in the first half of 2017.” “We are most pleased to enter the Asian market for the first time with Pharmatronic, a Korean organization committed to customer service excellence,” said Dr. Horst G. Zerbe, President and CEO of IntelGenx. “We will be working hard with our partners RedHill and Pharmatronic to bring our innovative product to market for patients in South Korea suffering from migraines. The execution of two commercialization agreements for RIZAPORT® in less than six months demonstrates our relentless execution of strategy to bring our innovative products to the global market.” RIZAPORT® (5 mg and 10 mg) was granted marketing authorization by the Federal Institute for Drugs and Medical Devices of Germany (BfArM) under the European Decentralized Procedure (DCP), in which Germany served as the Reference Member State for other European Union (EU) countries. This authorization was the first national marketing approval for RIZAPORT®. A first commercialization agreement was signed with Grupo JUSTE S.A.Q.F (Grupo JUSTE) for Spain and additional potential territories and, subsequently, a national Marketing Authorization Application (MAA) for RIZAPORT® was submitted by Grupo JUSTE in Spain under the European DCP. RedHill and IntelGenx expect to re-submit the RIZAPORT® New Drug Application (NDA) to the FDA in the first half of 2017 and subsequently receive a new PDUFA (Prescription Drug User Fee Act) date and are currently in discussions with potential commercialization partners for the U.S. market. About RIZAPORT® (RHB-103): RIZAPORT® is a proprietary oral thin film formulation of rizatriptan benzoate, a 5-HT receptor agonist and the active drug in Merck & Co.’s Maxalt®. RIZAPORT® 5 mg and 10 mg were approved for marketing in Germany in October 2015 under the European Decentralized Procedure. A New Drug Application for RIZAPORT® was also filed with the U.S. FDA in 2013 and a CRL was received in 2014. RedHill has entered into licensing agreements to commercialize RIZAPORT® in Spain (with Grupo JUSTE S.A.Q.F) and in South Korea (with Pharmatronic Co.). Rizatriptan is considered to be one of the most effective oral triptans, a class of molecules that constricts blood vessels in the brain to relieve swelling and other migraine symptoms. The worldwide annual sales of triptans were estimated to have exceeded $690 million in 20151. RIZAPORT® is based on IntelGenx's proprietary VersaFilm™ technology. It dissolves rapidly and releases its active ingredient in the mouth, leading to efficient absorption of the drug through the gastrointestinal tract. The administration method of the RIZAPORT® oral thin film, which does not require the patient to swallow a pill or consume water, along with its pleasant flavor, presents a potentially attractive therapeutic alternative for migraine patients, specifically for patients who suffer from migraine-related nausea, estimated to be approximately 80% of the total migraine patient population2 and patients suffering from dysphagia (difficulty swallowing). About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) is a biopharmaceutical company headquartered in Israel, primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill’s pipeline of proprietary products includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study and a completed proof-of-concept Phase IIa study for multiple sclerosis; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered uPA inhibitor, targeting gastrointestinal and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in Germany in October 2015. About Pharmatronic. Co: Pharmatronic Co. is a privately held pharmaceutical company headquartered in Seoul, South Korea which distributes exclusively licensed pharmaceutical products with innovative sales and marketing know-how. Since its establishment in 2005, Pharmatronic Co. has focused R&D and marketing resources on the specialized target field of neurology, ENT and urology, building a strong image as a leading provider in the pharmaceutical and healthcare industry. About IntelGenx: IntelGenx is a leading oral drug delivery company primarily focused on the development and manufacturing of innovative pharmaceutical oral films based on its proprietary VersaFilm™ technology platform. Established in 2003, the Montreal-based company is listed on the TSX-V and OTC-QX. IntelGenx highly skilled team provides comprehensive pharmaceuticals services to pharmaceutical partners, including R&D, analytical method development, clinical monitoring, IP and regulatory services. IntelGenx state-of-the-art manufacturing facility, established for the VersaFilm™ technology platform, supports lab-scale to pilot and commercial-scale production, offering full service capabilities to our clients. More information is available about the company at: www.intelgenx.com. 2 Lipton RB, Buse DC, Saiers J, Fanning KM, Serrano D, Reed ML. (2013) Frequency and burden of headache-related nausea: results from the American Migraine Prevalence and Prevention (AMPP) study, Headache. 2013 Jan;53(1):93-103. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to establish and maintain corporate collaborations; (vi) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (vii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (viii) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (ix) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (x) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xi) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xii) competitive companies and technologies within the Company’s industry; and (xiii) the impact of the political and security situation in Israel on the Company's business. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 25, 2016. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law.


Weise M.,Federal Institute for Drugs and Medical Devices | Kurki P.,Finnish Medicines Agency | Wolff-Holz E.,Paul Ehrlich Institute | Bielsky M.-C.,Medicines and Healthcare Products Regulatory Agency | And 2 more authors.
Blood | Year: 2014

Despite the establishment of a specific approval pathway, the issuance of detailed scientific guidelines for the development of similar biological medicinal products (so-called "biosimilars") and the approval of several biosimilars in the European Union, acceptance of biosimilars in the medical community continues to be low. This is especially true in therapeutic indications for which no specific clinical trials with the biosimilar have been performed and that have been licensed based on extrapolation of efficacy and safety data from other indications. This article addresses the concerns frequently raised in the medical community about the use of biosimilars in such extrapolated indications and explains the underlying scientific and regulatory decision making including some real-life examples from recently licensed biosimilars. © 2014 by The American Society of Hematology.


Xbrane has received advice from BfArM, the German Federal Institute for Drugs and Medical Devices, with regards to the clinical and regulatory aspects of the Company's planned submission of a Marketing Authorization Application (MAA) for Spherotide 1-month formulation for the European Union. A Market Authorization in EU would enable Xbrane to sell and market Spherotide in Europe and would serve as a base and facilitator for the approval process in other regions. The MAA will, according to the advice received by BfArM, be supported by a single pivotal clinical trial in prostate cancer patients. The clinical efficacy of Spherotide will be measured as testosterone suppression under castration level by day 28. The secondary endpoints as suggested by Xbrane were all accepted by BfArM. Xbrane estimates that the clinical trial will involve 150-170 prostate cancer patients and to be initiated first half of 2017. In accordance with Xbrane's commercialization strategy for Spherotide the study shall be co-funded by the future European sales and marketing partner. "We are happy to gain support for our regulatory and clinical strategy in discussions with BfArM. The advice was pragmatic and concrete and we are very confident that the discussed thresholds for efficacy are achievable. This allows us to proceed with all activities required for finalizing the MAA for the European Union, " Martin Åmark, CEO Xbrane Biopharma Xbrane plans to file a MAA under the hybrid pathway, directive 2001/83/EC article 10 (3), following the decentralized procedure with Germany as the Reference Member State (RMS), and including other main European countries. Spherotide is a generic to the drug Decapeptyl® with global sales of approximately SEK 4 billion. It is a formulation with long acting effect after injection with the active substance triptorelin and is used primarily in the treatment of prostate cancer, endometriosis and uterine fibroids. The drug is based on encapsulation of the active substance in biodegradable microspheres that degrade in the body after injection and create a long acting effect. Spherotide is the only generic to Decapeptyl®. About Xbrane Biopharma AB Xbrane is a commercial phase Swedish biopharmaceutical company specialized in High Demand Biosimilars and long acting injectables. Xbrane has world leading expertise in developing generics for long acting injectable drugs and proprietary high-yield protein expression technology for the development of biosimilars. Xbranes's headquarter is located in Stockholm and the company's in-house research and development facilities are in Sweden and Italy. Xbrane is listed at Nasdaq First North since February 3rd under the name XBRANE and Avanza Bank AB is Xbranes certified advisor. For more information see www.xbrane.com. For further information, please contact: Martin Åmark Chief Executive Officer M: +46 (0) 763-093 777 E: martin.amark@xbrane.com This information is information that Xbrane Biopharma AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 8:30 October 31 2016.


News Article | December 7, 2016
Site: www.nature.com

Steffen Schulz was completing his PhD in medical neuroscience at the Charité university hospital in Berlin when he realized he wanted more job security than academia could offer. He is now a drug-safety manager at a pharmaceutical company in Germany. Where do you work? I'm based in Berlin. I grew up, studied for my diploma and did my PhD here, and I'm still in the same area. How did you get your job? I actually got it before I finished my PhD. My wife was pregnant with twins and I didn't want another fixed-term contract or to be forced to move anywhere. I considered a postdoc, but that felt like a stopgap. So I applied for work at a large pharmaceutical company, and started a trainee position there before I submitted my thesis. Since then I've been made permanent, and then promoted. What do you do there? In the drug-safety department, we take messages from physicians, pharmacists and patients about side effects from our company's drugs. I record and analyse that feedback, evaluate the benefit-to-risk ratio and see if any changes should be made to the patient-information leaflet or if we need to do something more dramatic. The serious side effects are reported directly to health agencies — Germany's Federal Institute for Drugs and Medical Devices and the European Medical Agency. They can withdraw a drug from the market. What would you tell people who want to move out of academia? You can't apply early enough — it's worth trying even before you submit your thesis. Be aware of the different options. I hadn't heard of drug safety before I saw this job. And know your skills — most PhD students don't realize that they already have a lot of experience. Even managing experiments is a form of project management. That's valuable. This interview has been edited for length and clarity. For more, see go.nature.com/2fv6p2s


Eckstein N.,Federal Institute for Drugs and Medical Devices
Journal of Experimental and Clinical Cancer Research | Year: 2011

Breast and ovarian cancers are among the 10 leading cancer types in females with mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer malignant diseases, the war on cancer declared by Richard Nixon four decades ago seems to be lost. Approximately 21,800 women in the US will be diagnosed with ovarian cancer in 2011. Therefore, its incidence is relatively low compared to breast cancer with 207.090 prognosed cases in 2011. However, overall survival unmasks ovarian cancer as the most deadly gynecological neoplasia. Platinum-based chemotherapy is emerging as an upcoming treatment modality especially in triple negative breast cancer. However, in ovarian cancer Platinum-complexes for a long time are established as first line treatment. Emergence of a resistant phenotype is a major hurdle in curative cancer therapy approaches and many scientists around the world are focussing on this issue. This review covers new findings in this field during the past decade. © 2011 Eckstein; licensee BioMed Central Ltd.


Wiesner J.,Federal Institute for Drugs and Medical Devices
Journal of Ethnopharmacology | Year: 2014

Each application for authorisation of a medicinal product must be accompanied by the particulars and documents referred to in Directive 2001/83/EC on the Community code relating to medicinal products for human use. Details on the documentation needed for traditional herbal medicinal products (THMP) are given in article 16c of the above mentioned Directive. It is pointed out that a bibliographic review of safety data together with an expert report and additional data, if necessary, are required. The Committee on Herbal Medicinal Products (HMPC) provides in its "Guideline on the use of the CTD format in the preparation of a registration application for traditional herbal medicinal products" (EMA/HMPC/71049/2007 Rev. 1) guidance on how to present the information and the dossier needed for an application. There, in agreement with the Directive 2001/83/EC, a bibliographical review of safety data is required within the "Non-clinical Overview". However, it is assumable that for such products, with a long tradition of usage bibliographical information relating to non-clinical safety are available, even if incomplete or not in accordance with today's state of the art. In the "Guideline on non-clinical documentation for herbal medicinal products in applications for marketing authorisation (bibliographical and mixed applications) and in applications for simplified registration" (EMEA/HMPC/32116/2005) it is reflected how to deal with such an incomplete set of data for traditional herbal medicinal products and crucial information are highlighted. This article will focus on the explanation of the requirements needed for the non-clinical safety evaluation of THMPs and some detailed explanations of the performance and interpretation of the mutagenicity studies. © 2014 Elsevier Ireland Ltd. All rights reserved.


Siener R.,University of Bonn | Bangen U.,University of Bonn | Sidhu H.,Oxthera Inc. | Honow R.,Federal Institute for Drugs and Medical Devices | And 2 more authors.
Kidney International | Year: 2013

About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract, we assessed the role of O. formigenes in oxalate metabolism by evaluating its intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium oxalate stone formers, 26 tested negative for O. formigenes and were compared with the 11 patients who tested positive. Patients provided 24-h urine samples on both a self-selected and a standardized diet. Urinary oxalate excretion did not differ significantly on the self-selected diet, but was significantly lower in O. formigenes-positive than in O. formigenes-negative patients under controlled, standardized conditions. Intestinal oxalate absorption, measured using 13 C 2 oxalate, was similar in the patients with or without O. formigenes. Plasma oxalate concentrations were significantly higher in noncolonized (5.79 μmol/l) than in colonized stone formers (1.70 μmol/l). Colonization with O. formigenes was significantly inversely associated with the number of stone episodes. Our findings suggest that O. formigenes lowers the intestinal concentration of oxalate available for absorption at constant rates, resulting in decreased urinary oxalate excretion. Thus, dietary factors have an important role in urinary oxalate excretion. The data indicate that O. formigenes colonization may reduce the risk of stone recurrence. © 2013 International Society of Nephrology.


Alpha-1-proteinase inhibitor (α1-PI) is the most relevant protease inhibitor in the lung. Patients with hereditary deficiency of α1-PI suffer from an impaired hepatic synthesis of α1-PI in the liver and in consequence an insufficient concentration of the protease inhibitor in the lung followed by development of lung emphysema due to an impaired protease antiprotease balance and a local relative excess of neutrophil elastase (NE). In contrast, patients with cystic fibrosis (CF) are characterised by a normal synthesis of α1-PI and a severe pulmonary inflammation with a strong excess of NE in the lung followed by progressive loss of lung function. In principle, both patient groups may benefit from an augmentation of α1-PI. Intravenous augmentation, which is established in patients with α1-PI deficiency only, is very expensive, subject to controversial discussions and only about 2% of the administered protein reaches lung interstitium. Inhalation of α1-PI may serve as an alternative to administer high α1-PI doses into the lungs of both patient groups to restore the impaired protease antiprotease balance and to diminish the detrimental effects of NE. However, prerequisites of this therapy are the reproducible administration of sufficient doses of active α1-PI into the lung without adverse effects. In our review we describe the results of studies investigating the inhalation of α1-PI in patients with α1-PI deficiency and CF. The data demonstrate the feasibility of α1-PI inhalation for restoration of the impaired protease antiprotease balance, attenuation of the inflammation and neutralisation of the excess activity of NE. Likely, inhalation of α1-PI serves as cheaper and more convenient therapy than intravenous augmentation. However, inhalation will be further optimised by use of novel nebulisers and optimised breathing techniques. © I. Holzapfel Publishers 2010.

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