Who we are?

2. Whowe are? • Team ofspecialisedexperts • AllservicesforwholeEurope in oneplace • EU regulatoryknowledgeandstrategies • MA holding and support • EU/local RA and PHV contact

3. Our Services • Continuous support andupdatesdepending on EU legislation • Regulatoryservices • Medicinalproducts, medicaldevices • Cosmetics, foodsupplements • Veterinaryproducts • Education + trainings • ClinicalTrials • PASS - Post-AuthorisationSafetyStudies • Marketing + sales • Import/Distribution • Marketing

4. RA Services = Regulatory House

5. Our Services – Key Features • Partner/Products/Concept analysis • Identification of key issues and risks of market entry • Elaborating of possible scenarios and strategy alternatives • Quantification of alternatives • Value, Time, Risks • Evaluation of influence on • Product definition • Registration strategy • Pricing • Reimbursement • Follow up procedures

6. Scope of The Services in Regulatory Affairs • Consultation and registration services in the territories • EU countries • Russia • Ukraine • Strategy, Registration, Maintenance Services in • Human and veterinary medicinal products • All alternatives of registration procedures (National, CP, MRP, DCP) • Food supplements and novel foods • Medical equipments/devices • „Health“ cosmetics

7. Registration Files - Submissions • Compilation and evaluation • Completeness and quality check: pre-submission • PreparationofCTD files • Support in creating Module 1 for all procedures according national/EU requirements • Negotiations with authorities • DCP slots blocking and management • Transforming/ creating ofe-CTD format

8. e-CTD • The electronic Common Technical Document (e-CTD) is an interface for the pharmaceutical industry to agency transfer of regulatory information. The content is based on the Common Technical Document (CTD) format. • The e-CTD was developed by theICH as standard format for regulatory submissions in the Europe, USA and Japan.

9. RegistrationFiles - Text Management Compliance in each country • Patient Information Leaflet (PIL), Summary of Product Characteristics (SPC), packaging material (mock-ups) • Harmonization of textsaccording to: • Actual QRD format • Localrequirements • EU reference product (generics) • Mock-up creation • Translation of texts to all languages • Braille requirements The smooth pass of the texts fundamental part of instant national phase of registration

10. Complex Regulatory Maintenance Management • Variations • Communication with authorities • Renewals of MAs • Sunset clause monitoring and solving Professional maintenance managementsaved time, stress, money…

11. Pharmacovigilance • Pharmacovigilance monitoring of the products 24/7/365 • Non-stop services for receipt of adverse events signals • Proprietary PHV database • Literature search service • Safety studies /clinical trials support • Complex services of QPPV: • Creation and run of the PHV system according to current EU requirements • Electronic submission of ADRs/AEs to EMA/NA (MedDRA, EudraVig) • Compulsory regular PHV training of the staff • Electronic submission of product information to EMA database (XEVMPD)

12. OtherServices • Public information service • 24/7/365 patient service • Disabled people • Consultation services for • Patients • Health care professionals • Companies The role of pharmacovigilance is becoming extremely important part of the dailybusiness

13. ClinicalTrials

14. Clinical Trial Preparation • Feasibility studies, start-up support • Selection of qualified investigators and trial sites • Preparation of study documents (Protocol, Investigator´s Brochure, Informed Consent Form, questionnaires, manuals etc.) • Protocol and medical writing • Statistical support, clinical trial designing • Submission to regulatory authorities and ethics committees • Co-ordination of preparation works, investigator´s meeting

15. Monitoring and CT Management • Site management, communication with investigators, on-site activities • Trial monitoring in compliance with Good Clinical Practice (GCP) • Data management and statistical data processing • Identification of changes and evaluation of regulatory aspects • Supervisionof the progress of a clinical trial • Supportfor fast recruitment • Ensuring protocol compliance • Applying SOPs, GCP and applicable regulatory requirements • Setup of adequate procedures for quality control and quality assurance

16. MedicalServices Support of the investigators • Preparation of Standard Operating Procedures • Good Clinical Practice trainings • Good Laboratory Practice trainings • Good Manufacturing Practice for Advanced Therapies • Legal aspects of CT, data protection, insurance Medical Services • Medical support of project teams • 24/7 medical support, ongoing medical safety review • Medical review of clinical study reports • Medical expert opinion • Medical reporting (interim, final reports, safety reports)

17. Pharmacovigilance , Risk Management • QPPV service • Immediate report of serious adverse events to sponsor • Reporting of SUSARS and all safety issues tocompetentauthority and ethics committee • Submission of annual safety reports to competent authority and ethics committee • Transmission of safety reports to investigators • Immediate hazard management • Risk management plan • Continuous follow-up and evaluation of risks • Quality assurance and Quality Control, QA/QC Audits

18. PASS

19. Post-AuthorisationSafetyStudies (PASS) • A post-authorisationsafety study (PASS) isdefined in Article 1(15) of Directive 2001/83/ECas any study relating to anauthorisedmedicinalproductconductedwiththeaim of identifying, characterisingorquantifying a safety hazard, confirmingthesafety profile of themedicinalproduct, or of measuringtheeffectiveness of risk-management measures. • PASS are designed to ensurethatmedicinalproducts are monitoredforlong-term safetyandeffectiveness in RoutineClinicalPracticeandmaybeinitiated, managedorfinanced by MAH voluntarily, orpursuant to anobligationimposed by a competentauthority. • PASS – Critical New Tool in searchingfor „MissingInformation“

20. PASS - Services PASS Management • Definitionofscientificformat of protocols, abstractsandfinal study report for non-interventional PASS • IdentificationoftheRequirementsandKeyelementsfor PASS • CreatingGuidance on Effectiveness of Risk Minimisation • Establishing monitoring system – GVP (Good Pharmacovigilance Practice) • E-register of non-interventional PASS maintained by theAgency • Publication of Final Study Report PASS On-siteservices • ON-SITE preparation of PASS (including on-sitetraining, contractissueetc.) • ON-SITE Data Management and Data Collection of PASS • e-CRFsservices, Statisticalanalysis • Preparing FINAL Study Report

21. Education & Training

22. Education & Training Regulatory affairs excellence ismainlydriven by knowledge – let´s beup to dateandlearneffectively • Life Cycle of Medicinal Products • Biostatistics • GCP course • Coordination of the clinical trials Allcourses are provided in co-operationwith PharmAroundeducationplatform www.pharmaround.com

23. Marketing + Sales

24. Market Access • Market analysis and market environment • Market Access strategy – reflecting actual and upcoming legislation development and „current“ practices • Pharmacoeconomic analysis • Budget impact • Cost effectiveness • Cost containment….. • Preparation and submission of application for • Maximum price • Reimbursement • Organisation of „patient registries“ • Management of„life cycle“ of the reimbursement/price

25. Knowledge - Creativity - Dedication - Success Committed to Your Success Slunná 16, Brno, 617 00CzechRepublic www.asamuel.eue-mail: office@asamuel.eutelefon: +420 534 008 052Fax: +420 545 233 606