Horst Kastrup September 8, 2015 The “T” in PETD

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Some data regarding the environment Company: Expected net sales in 2015: > 2 billion USD Employees (worldwide) end of 2014: approx Subsidiaries in more than 60 countries, products sold in more than 150 countries Company grows by acquisition of companies and products (company acquisitions include ASTA Medica, 3M Pharma, Valeant Europe, Tropon (part of Bayer group), Madaus, Rottapharm) Current portfolio: more than 80 originator products (substances) 3 The “T” in PETD

Some data regarding the environment Focus on Europe (net sales 1 st half of 2105): Europe63 % USA16 % Emerging markets18 % R x Medicinal products 62 % C x / OTC Medicinal products/ medical devices36 % 4 The “T” in PETD

Some facts regarding the environment Company includes: Marketing & sales subsidiaries, usually including regulatory/ pharmacovigilance functions Manufacturing plants (Europe, USA) Pharmaceutical development unit Corporate functions in Sweden, Germany, and Italy (including C(D)RA, CPV, Clinical Development, CQA) More than 100 contract manufacturers, many scientific contractors 5 The “T” in PETD

Role: Senior Regulatory Advisor including - Identification of new challenges due to expected/new regulatory requirements/ legislation - Proposals for the implementation of new processes to meet new requirements - Presentations/ trainings for regulatory staff and other departments, which are affected by new requirements 6 The “T” in PETD

Routine training: SOP training (regulatory SOPs) Training of new staff and annual refreshing regarding confidentiality rules, work accident prevention, data protection rules, confidentiality obligations, equal rights principles, environmental protection rules & program, reporting obligations regarding product risks 7 The “T” in PETD

Training following company acquisitions (concerned staff in all subsidiaries), new contractors etc.: SOP training (regulatory SOPs) Training regarding company confidentiality rules, work accident prevention, data protection rules, confidentiality obligations, equal rights principles, environmental protection rules & program, reporting obligations regarding product risks Training regarding standard procedures and business principles in Regulatory Affairs, which are not written down in SOPs 8 The “T” in PETD

Training of junior staff or new staff from other industries (not limited to RA) Basic training (focus on ICH/ European requirements) on e.g. - CTD format and content - Administrative procedures at the agencies (new authorizations, update of licenses, notification obligations) - Search strategies for professional information (including use of authority databases, websites of legislative bodies, Cortellis database, RSS feeds …) 9 The “T” in PETD

Training on other GxP requirements Training on PV, Clinical and Pharmaceutical Development, Quality Assurance, GMP routine topics is provided by trainers from CPV, CD, CPD, CQA, Manufacturing (includes e.g. training of sales force regarding reporting of product risks) Training regarding new challenges in these areas is provided by CDRA experts, if requested by the concerned departments 10 The “T” in PETD

Training due to the company focus on Europe Most regulatory and PV material for submission purposes is prepared based upon EU requirements. To enable subsidiaries outside the EU to communicate their specific need (if not yet included in tabulations with country specific needs), basic training regarding ICH/ EU document requirements/ EU regulatory procedures is provided to RA/PV staff outside the EU 11 The “T” in PETD

Planning of training Training matrices are provided for GxP SOP training (mandatory) Similar training matrices are provided for other topics, if reasonable (or required) 12 The “T” in PETD Scientific staff/ managers dep. 1 Non-scientific staff/ specialists dep. 1 Scientific staff/ managers dep. 2 Non- scientific staff/ specialists dep. 2 SOP XXXM-Mv SOP YYY--MM SOP ZZZM---

Examples of training topics provided during the past two years or scheduled for 2015 (SOP training not included) 13 The “T” in PETD

Basic training (for new staff) Purpose: to understand, that medicinal products are special goods, and why manufacture and distribution of a medicinal product is (and was) subject to special supervision by the authorities 14 The “T” in PETD

Quality issues  New Good Distribution Practice Guideline (new requirements for wholesale function, qualification of suppliers)  New GMP requirements for APIs  Risk adjusted GMP for excipients  ICH M7 update (potential genotoxic/ carcinogenic impurities)  ICH Q3D update (elemental impurities)  Updates of some chapters of EU Eudralex GMP guideline 15 The “T” in PETD

Quality issues – focus on falsified/ counterfeit medicines  Falsified medicines inside and outside the legal distribution chain  Anti-counterfeit requirements in relevant markets (Turkey, Argentina, China, South Korea, Brazil, Saudi Arabia, US, …)  Requirements due to anti-counterfeit legislation in Europe (unique identifier, tamperproof closure) 16 The “T” in PETD

Pharmacovigilance issues  New procedures with the involvement of the Pharmacovigilance Risk Assessment Committee (PRAC) at the EMA  Understanding and filling of the extended EudraVigilance Medicinal Products Dictionary (xEVMPD), upcoming implementation of the ISO norms for the description of medicinal products (IDMP)  Electronic EU pharmacovigilance reporting  New labeling requirements due to the PV legislation  Understanding the new EU PV fees/ calculation of the fees/ budgeting of expected fees  Switch from PSUR to PBRER format and new EU submission time schedules 17 The “T” in PETD

Regulatory issues  New electronic filing portals  New variation classification rules/ new procedural rules for variations  New regulatory reporting obligations (product authorizations/ withdrawals outside the EU)  Demarcation medicinal products/ medical devices/ biocides/ cosmetics/ food supplements … Regulatory issues related to medical devices  Pending EU legislation – upcoming EU regulation on devices/ focus: new classification rules/ new certification requirements 18 The “T” in PETD

Clinical Development issues  New EU Regulation on Clinical Trials/ new rules for clinical trial applications  EU Clinical trials data base  Transparency rules for clinical trials/ trial reports Pediatric medicines  Pediatric trials EU database  Pediatric development plans (prerequisite for approval of new medicinal products with patent protection) 19 The “T” in PETD

Trademark issues  Handling of notifications of parallel imports/ compliance check of PI samples Labeling  Child proof/ senior citizen friendly packaging  Optimization of lay-out to avoid medication errors Environmental issues  Assessment of environmental impact of new products  Sustainability of packaging materials/ compliance with EN/ ISO standards  Sustainability of products and services in the framework of the revised ISO certification 20 The “T” in PETD