European Medicines Agency approvals

Circadin is a prolonged-release tablet containing melatonin 2 mg. It has received European Medicine Agency approval for treatment of primary insomnia. Adverse reactions are uncommon, but include headache, pharyngitis, back pain, and weakness. There do not appear to be withdrawal effects. 

Two forms of pegylated IFN-a have been approved by the Food and Drug Administration (FDA) and by the European Medicines Agency (EMEA) for the... 

The European Medicines Agency and the new EU drug approval systems... 

In Europe, inspections are conducted by member states on behalf of the European Union. For drugs approved under the centralized procedure, inspections are coordinated by the European Medicines Agency (EMEA refer to Sections 7.3 and 8.3). For countries that are members of the Pharmaceutical Inspection Cooperation Scheme (PIC/S see Section 7.13), there is mutual recognition of inspections performed by members. 

Vinblastine (6.73) is an antimitotic drug that prevents polymerization of tubulin (Figure 6.26). When incubated with tubulin, vinblastine complexes in a 1 1 ratio with tubulin proteins. By blocking polymerization, vinblastine prevents microtubule formation and therefore mitosis. In contrast, paclitaxel (Taxol, 6.74) and epothilone B (6.75) stabilize aggregated tubulin. As a result, in the presence of paclitaxel and epothilone B, cells form static bundles of microtubules that are nonfunctional. Vinblastine and paclitaxel are both approved for clinical use against cancer. Ixabepilone (6.76), an analogue of epothilone B (6.75), has been approved by the FDA for treatment of certain forms of breast cancer. The European Medicines Agency (EMEA) did not approve ixabepilone out of concern over severe side effects.27... 

Since the first introduction of insulin to treat diabetic patients in 1923, much effort has been made to seek alternative convenient and painless routes for insulin administration instead of daily injections. In this respect the pulmonary route has received the most attention, and substantial evidence has shown inhaled insulin to be an effective, well-tolerated, noninvasive alternative route [53-56]. Insulin therapy is required for patients with type 1 diabetes. Although some patients with type 2 diabetes can control their disease with oral antidiabetics, many will eventually also require insulin. Thus, inhaled insulin shows promise for type 2 diabetic patients [54, 56]. There are two principal inhalation systems for insulin, namely aqueous solution and dry powder. The dry powder form (Exubera ) has been approved by FDA and the European Medicines Agency (EMEA) in January 2006. 

Centralized Procedure (CP) This is the procedure of most interest for biopharmaceuticals, as this is the mandatory route for review and approval of such drugs in the European Union. In the centralized procedure a single application is submitted to the European Medicines Agency (EMEA). A variety of presubmission activities, starting six months before the intended start date of the centralized procedure, are required [8], Two initial assessments by a Rapporteur and Co-rapporteur national authorities (one from each of two member states chosen by the EMEA) are made, leading to Day 80 Critical Assessment Reports. A consolidated list of questions (LoQ) is provided to the applicant at Day 120 when there is a clock stop, normally of three months, to allow the preparation and submission of responses. Following satisfactory negotiation of other steps in the procedure, the Committee on Human Medicinal Products will recommend authorization at Day 210, with authorization by the Commission at Day 277. 

In the following sections the testing strategies that have been applied in support of the approved biopharmaceuticals are reviewed and discussed in terms of the relevance to the evaluations of human safety and the lessons that have been leaned for future reproductive developmental toxicity testing. All information provided in the following narrative, unless otherwise referenced, have been extracted from the FDA summary basis of approval information www.fda.gov, the European Medicines Agency (EMEA) centrally authorized... 

This chapter provides a survey of US marketed biopharmaceuticals approved over the past 20 years. It is a simply a profile of the species and types of toxicology studies done for each drug for marketing approval. For a complete list of all preclinical studies for a biopharmaceutical, the reader is directed to the Web sites of the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). 

Source The main source of the information in this table is either the Food and Drug Administration (FDA) Web site or European Medicines Agency (EMEA) Web site. For biopharmaceuticals approved before 1995 limited information is available so the author used the most recent label (package insert) to derive the reproductive, carcinogeneticity, and genetic toxicology studies completed for marketing approval. 

An MAA for vinflunine (Javlor ) 43 (Pierre Fabre) has been submitted to the European Medicines Agency (EMEA) for the treatment of various cancers.103 Pierre Fabre had been developing vinflunine 43104 106 in the USA in partnership with Bristol-Myers Squibb for the treatment of breast, bladder and lung cancers but development was halted in late 2007.107 Four Vinca-type alkaloids have been approved for cancer treatment vinblastine 44108 and vincristine... 

An inhaled form of insulin has been approved by The European Medicines Agency for use in adult patients with diabetes mellitus. 

---