ACONDICIONAMIENTO DE RECINTOS- CONFORT 1. AIRE ACONDICIONADO

In the Directive 2001/83/EC, articles 101 to 108, the EU gives instructions how to handle the surveillance of authorized medicinal products. According to this Directive all Member States

152 _{J. H. Kim and A. R. Scialli, "Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease} (Oxford Journals; Toxicological Sciences Volume 122, Issue 1, pp. 1-6)," 2 April 2011. [Online]. Available: http://toxsci.oxfordjournals.org/content/122/1/1.full. [Accessed 22 November 2013].

153 _{"The Importance of Pharmacovigilance - Safety Monitoring of medicinal products, WHO 2002," [Online].} Available: http://apps.who.int/medicinedocs/pdf/s4893e/s4893e.pdf. [Accessed 29 October 2013]. 154 _{"The Importance of Pharmacovigilance - Safety Monitoring of medicinal products, WHO 2002," [Online].} Available: http://apps.who.int/medicinedocs/pdf/s4893e/s4893e.pdf. [Accessed 29 October 2013]. 155 _{"WHO-UMC homepage," [Online]. Available: http://www.who-umc.org/DynPage.aspx. [Accessed 30} October 2013].

156 _{"The Importance of Pharmacovigilance - Safety Monitoring of medicinal products, WHO 2002," [Online].} Available: http://apps.who.int/medicinedocs/pdf/s4893e/s4893e.pdf. [Accessed 29 October 2013]. 157 _{"WHO - Pharmacovigilance," [Online]. Available:}

http://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/. [Accessed 30 October 2013].

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of the European Union and marketing authorization holders of medicinal products have to establish a pharmacovigilance system in order to collect and to evaluate all information about potential risks regarding medicinal products, with particular reference to adverse reactions and interactions. [1]158 _{However, not only information about adverse drug reactions under} normal conditions of use shall be in scope of the pharmacovigilance system, but also any data on misuse and abuse of the drugs that may have an impact on the benefit-risk balance of the products. [1]159 _{Such information is summarized in a risk management plan including} the safety risk assessment and defined risk minimization measures. The marketing authorization holders are expected to provide a succinct update of the worldwide safety experience of a medicinal product together with a critical evaluation of its benefit-risk balance considering new or changing information to the competent authorities at defined time points post-authorization. These reports are called periodic safety update reports (PSURs) [89]160_, nowadays also denoted as periodic benefit-risk evaluation reports (PBRERs) since the reports provide a greater emphasize on the benefit of medicinal products. [93]161

Every marketing authorization holder is obliged to appoint a qualified person for pharmacovigilance (QPPV) who is responsible for the permanently and continuously post authorization surveillance. [1]162 _{The duties and responsibilities of the QPPV are clarified in} the Directive 2001/83/EC, as well. Beyond the territory of the EU the Directive affects also all other countries. Marketing authorization holders located in non-EU countries have reporting requirements towards the competent authorities within the EU with respect to medicinal products that are authorized in at least one EU country. The marketing authorization holder is required to record and report suspected serious adverse reactions promptly to the competent

158 _{"Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001," (OJ L 311,} 28.11.2001, p. 67). [Online]. Available: http://ec.europa.eu/health/files/eudralex/vol-

1/dir_2001_83_consol_2012/dir_2001_83_cons_2012_en.pdf. [Accessed 16 January 2015].

159 _{"Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001," (OJ L 311,} 28.11.2001, p. 67). [Online]. Available: http://ec.europa.eu/health/files/eudralex/vol-

1/dir_2001_83_consol_2012/dir_2001_83_cons_2012_en.pdf. [Accessed 16 January 2015]. 160 _{"Volume 9A of The Rules Governing Medicinal Products in the European Union - Guidelines on} Pharmacovigilance for Medicinal Products for Human Use," September 2008. [Online]. Available:

http://ec.europa.eu/health/files/eudralex/vol-9/pdf/vol9a_09-2008_en.pdf. [Accessed 30 October 2013]. 161 _{European Medicines Agency, "ICH guideline E2C (R2) on periodic benefit-risk evaluation report (PBRER),"} January 2013. [Online]. Available:

http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2012/12/ WC500136402.pdf. [Accessed 27 January 2014].

162 _{"Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001," (OJ L 311,} 28.11.2001, p. 67). [Online]. Available: http://ec.europa.eu/health/files/eudralex/vol-

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authority, latest within 15 calendar days163_{, regardless whether the incident occurred within} the territory of an EU Member State or in a country outside of the EU. [1]164

In the context of the already mentioned Pharmaceutical Package the new pharmacovigilance legislation, comprising a directive (Directive 2010/84/EU) and a regulation (Regulation EU No 1235/2010), was adopted by the European Parliament and the European Council in December 2010. The new legislation serves the purpose to strengthen and to simplify the European pharmacovigilance system and to provide the public with helpful information about the benefit-risk aspects of medicinal products. In October 2012, the new pharmacovigilance legislation was amended again by Directive 2012/26/EU and Regulation EU No 1027/2012. The amendment’s purpose is to further support the protection of patient health. It refers e.g. to the marketing authorization holder’s obligation to notify the EMA immediately in case of the withdrawal of a medicinal product. The notification also has to include the reasons for the withdrawal of the respective product from the market. [94]165 _{To provide specific guidelines} regarding the provisions related to the EU safety monitoring system and the requirements with respect to pharmacovigilance procedures, the EMA released the good pharmacovigilance practice (GVP) guidelines which comprise multiple modules. 12 modules (I – X, XV and XVI) are already effective. 3 modules (XI, XII and XIV) are still in development, while the development of module XIII was stopped. Its contents will be included in module XII. [95]166 _{Thus, the document Volume 9A of "The rules governing medicinal products in the} European Union - Pharmacovigilance" is being replaced by the 15 GVP modules. [96]167 In Germany the handling of pharmacovigilance is settled in the AMG, §§ 62-63c. The German competent authorities such as the BfArM and the Paul-Ehrlich-Institute (PEI) collaborate closely and interact with the WHO, the EMA and FDAs of other countries, amongst others. [53]168 _{Every health facility, e.g. pharmacies and medical practices, is}

163 _{15 calendar days for serious cases, 90 calendar days for non-serious cases}

164 _{"Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001," (OJ L 311,} 28.11.2001, p. 67). [Online]. Available: http://ec.europa.eu/health/files/eudralex/vol-

1/dir_2001_83_consol_2012/dir_2001_83_cons_2012_en.pdf. [Accessed 16 January 2015]. 165 _{European Medicines Agency, "2010 Pharmacovigilance Legislation," 2013. [Online]. Available:}

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000492.jsp&mid= WC0b01ac058033e8ad. [Accessed 3 December 2013].

166 _{European Medicines Agency, "Good Pharmacovigilance Practices," 2014. [Online]. Available:}

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_00034 5.jsp. [Accessed 31 January 2015].

167 _{European Commission, "The EU Phamacovigilance System," 2013. [Online]. Available:}

http://ec.europa.eu/health/human-use/pharmacovigilance/index_en.htm. [Accessed 3 December 2013]. 168 _{"German Medicinal Products Act; Gesetz über den Verkehr mit Arzneimitteln (Arzneimittelgesetz - AMG),"} as announced on 12 December 2005 (Federal Law Gazette I p. 3394); last amended on 10 October 2013 (Federal Law Gazette I p. 3813). [Online]. Available: http://www.gesetze-im-

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obliged to report any adverse drug reaction, which is brought to their attention, pursuant to the graduated scheme which is given by governance as a guide so that everyone knows to whom the information has to be provided. [53]169

The law includes special regulations with respect to pharmaceutical companies. According to § 63a every company must implement and continuously run a pharmacovigilance system. A named qualified person, responsible for pharmacovigilance, has to account for the required qualification and to ensure the pharmacovigilance system is managed according to the legislative regulations. Furthermore, the qualified person is the interface to the competent authorities. [53]170

169 _{"German Medicinal Products Act; Gesetz über den Verkehr mit Arzneimitteln (Arzneimittelgesetz - AMG),"} as announced on 12 December 2005 (Federal Law Gazette I p. 3394); last amended on 10 October 2013 (Federal Law Gazette I p. 3813). [Online]. Available: http://www.gesetze-im-

internet.de/bundesrecht/amg_1976/gesamt.pdf. [Accessed 26 November 2013].

170 _{"German Medicinal Products Act; Gesetz über den Verkehr mit Arzneimitteln (Arzneimittelgesetz - AMG),"} as announced on 12 December 2005 (Federal Law Gazette I p. 3394); last amended on 10 October 2013 (Federal Law Gazette I p. 3813). [Online]. Available: http://www.gesetze-im-

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CHAPTER TWO – PHARMACEUTICAL COMPANYS’ ANTI-COUNTERFEITING MEASURES

As counterfeit medicines pose a major risk to the safety of patients, and thus to public health, pharmaceutical companies should endeavor to contribute to the combat against counterfeiting of medicinal products, far beyond the obligations that are laid down in statutory provisions. There are several options for pharmaceutical companies to implement anti- counterfeiting measures. Some examples of these measures are explained below including data monitoring and evaluation, collaboration with authorities, investigative measures, legal measures, technological measures, awareness-raising, review of established anti- counterfeiting procedures and activities.