We embrace research and science, providing innovative products and integrated services to improve people s quality of life.

Transcription

1 Services Book 2016

2 Our DNA Philosophy We embrace research and science, providing innovative products and integrated services to improve people s quality of life. Vision We aspire to be one of the best healthcare companies in the world, providing leading pharmaceutical innovations and solutions, sustaining our impressive growth rates and securing customer preference. Mission We strive to make a difference in people s lives though leading innovation in medicine and research driven activities. We are firmly committed to continually excel in developing, manufacturing and commercializing advanced pharmaceutical products and services, made effectively and affordably available. Pharmathen Services 2

3 Contents Company Profile Third Party Auditing Regulatory Affairs Drug Safety & Pharmacovigilance Scientific Operations Intellectual Property Quality Management & Assurance Quality Control Pharmathen Services 3

4 We deliver high quality products and solutions with return to our customers and society Pharmathen Services 4

5 Company Profile Pharmathen, located in Athens, Greece, was founded in1969 as a private pharmaceutical company, and is focused on developing and marketing innovative health care products, with a strong position in generics. With a long history of development and manufacturing of pharmaceutical products, Pharmathen has emerged as one of the largest development companies in Europe. Today, the in-house development products of Pharmathen are registered in all major EU markets and licensed out to the largest pharmaceutical companies in Europe, Canada, Australia, South Africa and the United States. In addition, Pharmathen is able to provide a complete backwardly integrated service to its clients, from the synthesis of the API, to the formulation and finally to the production of the finished product. Furthermore, Pharmathen through its accumulated experience and know-how, is now able to provide, apart from products and advance technological solutions, various independent services to its partners, which are vital to the pharmaceutical industry worldwide. In this booklet you will find detailed descriptions, as well as therelevant contacts for these services, which include: Medical & Pharmacovigilance, Third Party Auditing, Regulatory Affairs, Quality Management & Quality Assurance, Quality Control, Intellectual Property, and Scientific Operations. Pharmathen Services 5

6 Third party Auditing Services Contacts: For details and inquiries, please contact our Head of International Audits & Compliance via or by phoning or Pharmathen Services 6 6

7 Third party audit (TPA) - GMP services Pharmathen offers professional services of conducting GMP audits, in particular APIs, to support Marketing authorization / Manufacturing license holders to comply with Article 46f of the Directive 2001/83/EC & 2001/82/EC and the rules governing Medicinal Products in the European Union, Volume 4 Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use, Part II (formerly Annex-18), Basic requirements for Active Substances Used as Starting materials The audit program of TPA services is in line with EU directives (Article 46f of 2001/83/EC) of API GMP expectations, commission delegated regulation (EU) No 1252/2014 of supplementing Directive 2001/83/EC & as per European Medicine Agency (EMA) guidance on the use of GMP compliant APIs manufactured in GMP compliant sites verified by the MA holder,; EMA/196292/2014, 21 May 2014, Guidance for the template for the qualified person s declaration concerning GMP compliance of active substance manufacture (the QP declaration template); European Medicines Agency (EMA) directive dated 21 May 2014 of EMA/334808/2014, Qualified Person s declaration concerning GMP compliance of the active substance manufacture The QP declaration template & EudraLex The Rules Governing Medicinal Products in the European Union Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Part 1 Chapter 5: Production : Starting Materials # 5.27 & Key advantages: Pharmathen s TPA services help the applicant of a marketing authorization or a manufacturing authorization holder to issue a declaration that the active substance(s) concerned has/have been manufactured in accordance with above directives. Pharmathen s TPA services are in line with the EMA (European Medicine Agency) GMP inspection group s aspirations, meaning that the results of an audit conducted by the third party are credible thus waiving the need for an audit conducted by the manufacturing authorization holder itself. Pharmathen Services 7

8 Brief synopsis on Pharmathen s TPA services: The audit program is a comprehensive service beginning with the pre-audit evaluation, followed by the actual conduction of the audit and detailed reporting, until the follow-up of formal audit observation closure/s. It also involves re-audit(s) or compliance audit(s) as and when required, and as per the frequency and requirements of our clients. Our experienced International Audit team is highly qualified and experienced in conducting Audits and reporting, having already conducted more than 1000 audits covering not only APIs, but also extending into finished dosage forms, packaging and laboratory operations, sterile products and starting materials like KSM, advanced intermediates (chemicals) etc. These audits so far have been conducted all across Asia, EU and the US. You can feel assured of the services offered as they are based on our fundamental principle, Commitment in dependability and reliability. Please find attached a short presentation that gives a more detailed description and the overview of our services. Auditing Program Report Structure Audit Report Format consisting of following key levels & types * 1) Audit Report AR Main section with 9 attachments 2) Attachments (AT-1 to AT-9) on each section described individually, with AT-1 to AT- 8 being systems specific, AT-9 is product specific, AT-10 only for sterile specific) Note: By this concept, each product details (narration as well as product specific observations) shall be kept separately as stand-alone such that any customer who is interested in a particular product shall be delivered 2-sets, i.e. 1 with systems specific and 1-product specific, and therefore the integrity of each product information is protected and it is not disclosed. This is giving consideration to the multiple products and different customers encountered and hence not to give unnecessary irrelevant extra info etc. 3) Audit Report Cross-reference file (pre-audit preparation data) ARC 4) Audit Report Supporting data release check-list (post-audit annexure data) ARS 5) Audit Report Release check-list (formal release) ARR 6) Annexure in support of report additional stand-alone files as listed out in ARS and ARR with previous audit references etc. Pharmathen Services 8

9 Total main files, supported by several reference & annexure files Summary: Overall it is like a Plant Master File with exhaustive information compiled as much as possible to make it a comprehensive package in totality. * Audit Report Package and Agreement Templates are available on request Synopsis International Audit Team placed strategically in India In line with the EMEA GMP inspection group s aspirations on 3rd party audits Expanding horizons to meet global demands Committed to be dependable & reliable with trustworthiness to partners Track Record Combined audit experience of more than 1000 audits Total hands-on industrial experience of 100 years Audits conducted so far across Asia, Europe, Mexico and US Range of audits cover entire Pharmaceutical supply chain, from API to finished dosage, to sterile, to packaging, to laboratory Extended to clinical (CRO & BA-BE) outsourced History Established in December 2007 to offer service to industry Continued relationship with several clients since establishment Signed exclusive arrangement with leading Generics Companies globally Existing clients from EU, US and Canada comprising of leading Global Generic pharmaceutical companies Client requests include new enquiries & repeat interests Pharmathen Services 9

10 Pharmathen Services 10 Pharmathen s Regulatory Affairs has more than 20 years of experience in regulatory submissions worldwide.

11 Regulatory Affairs Services Our primary focus is to use our expertise to ensure we globally provide high quality regulatory affairs advice, from the early concept stage and strategy building, up to and beyond dossier submission and marketing authorisation ensuring that your products are not only marketed by the quickest and most cost effective route, but remain on the market. Regulatory Services Strategic and product planning Regulatory submission Lifecycle management Regulatory support Strategic and product planning The Pharmathen team, with its extensive experience in Regulatory Affairs and strong scientific backgrounds, understands and can interpret regulatory scenarios for its clients and provides a wide range of approval strategies as well as the most advantageous authorisation routes to ensure a product reaches the market fast and efficiently. Some of our services include: Regulatory project management and a wide range of approval strategies to ensure a product reached the market fast and efficiently Continuous Regulatory support and guidance, with well defined clear objectives and appropriate milestone allocation Regulatory Intelligence Regulatory Documentation and full medical writing activities (Quality, Clinical, generating SmPCs/PILs, Labelling) High profile meetings with Authorities and thorough Agency interactions, liaising with a established network of Agency contacts Regulatory Submission Pharmathen Services 11

12 When it comes to dossier compilation and submission, Pharmathen knows how to ensure success. Our high level of expertise with pharmaceuticals, in liaison with our scientific writers and supported by the strong technical infrastructure result in state of the art dossier compilation. Pharmathen can provide assistance with the following: High quality CTD / ectd compliant dossier preparation to ensure efficient review by the Regulator (for all countries requiring a ectd submission including EU, GCC and KSA countries, South Africa etc) Extedo ectd Manager Software ICH compliant Review of raw data and reports for inclusion in the regulatory submission Worldwide Marketing Authorisation applications (including National, MRP, DCP, CP) Review of Authority Assessment Reports and preparation of quality responses with the appropriate level of detail Preparation of clinical and non-clinical overviews, and full scientific support Interaction with Authorities to establish crucial quality, clinical and non-clinical plans of action (Scientific Advice) Preparation and evaluation of toxicological reports Genotoxicity evaluation Preparation of product information texts including user tested patient leaflets WHO Prequalification of Medicines Programme EMA Article 58 procedure Pharmathen Services 12

13 Life cycle management The Pharmathen Regulatory team appreciates that a Marketing Authorisation requires continuous monitoring and provides continuous support to the client, by developing strategies for post approval activity. Pharmathen is always in the lead in assessing the risk-benefit profile of each medicinal product, guaranteeing you medicinal products safety at all times: Organisation and coordination of post approval activity (PSURs, Type IA/IB/II Variations including Grouping and Worksharing, Renewals, commitments) and all associated strategies. Preparation and submission of supporting data. Proactive approach in reviewing data and organising appropriate meetings with Regulators to address future issues. Regulatory Support The Regulatory Affairs department extends its services to excellent due diligence assessment when a client considers licensing in a novel product for which in-house expertise may not be available to assess the regulatory implications of the product. With our accumulated experience we can help clients evaluate business opportunities, and provide reassurance on the superiority of the dossier and minimise the risk of unsuccessful investments. Our due diligence services include: Assessment of product development strategies, evaluation of possible regulatory obstacles and perspectives for marketing authorisation Business opportunities for novel pharmaceutical products Feasibility studies to assess regulatory implications of alternative production processes For more information please feel free to contact us: Ms Stavroula Motsiou smotsiou@pharmathen.com Pharmathen Services 13

14 Drug Safety & Pharmacovigilance Services Driven by expertise, high level operational flexibility, and an unparalleled client-oriented approach, we are in position to strategically interact with a diverse client portfolio to provide top-class drug safety services. Whether it is a customized service for a small pharma or a full PV package allocation for a market leader, our goal remains unchanged: continuous, effective and qualitative surveillance of the safety profile of your products to ensure peace of mind with regulatory compliance and uneventful market presence, regardless of your operating business model and capacity. We have invested heavily in IT systems to work with cutting edge technologies in order to minimize unnecessary workload and optimize our procedures. All safety and regulatory systems are installed in-house at Pharmathen s data centre. Pharmathen Services 14 Our continuing expansion in terms of operations, technology, projects, market penetration and clientele is our unambiguous credential: we have become exceedingly efficient at meeting our goal!

15 Our track record in brief Our Pharmacovigilance system is fully aligned with ICH and other international standards, running on an ISO 9001:2008 certified QMS, and has repetitively been audited successfully by European Regulators and major stakeholders in the pharma industry over the last years. We boast an exceptional track record of meeting quality standards in our deliverables with a proven capacity for large volumes of work. Some of our major projects include: PSUR writing, retrospective literature Timely creation of 60 PSURs within 2 months on behalf of one of our major clients for urgent submission to their local Authority. No safety data from the medical literature were available, so full retrospective screening of a broad time period along with review and classification of results was also necessary. Case reports Relief of significant backlog ICSR volume for an affiliate identified during an Authority Inspection. By employing smart project design, sophisticated in-house multilevel deduplication techniques, critical quality review of clean output and efficient data handling for the transfer later on, we completed the project in 50% of the overall time requested by the Inspector. Drug repurposing Combining seemingly unrelated data from our databases to identify the use of a well-established molecule for the off-label treatment of perinatal asphyxia, an orphan disease that lacked effective pharmaceutical treatment. We have filed the relevant dossier and managed to obtain an orphan drug designation shortly after. Literature strategy, data management, proposal writing Submission of two prime quality service delivery proposals to the EMA for the screening of medical literature for case reports and processing of the same, and for the Eudravigilance data cleanup and management. Both proposals ranked exceptionally high (in top three). Pharmathen Services 15

16 A synopsis of our operations Our safety surveillance portfolio comprises thousands of medicinal products stemming from the worldwide monitoring of around 200 active substances of own and client s medicinal products. We currently assume full pharmacovigilance services for dozens of third parties, maintain XEVMPD datasets for thousands of medicinal products and have implemented hundreds of safety agreements actively implicating Pharmathen on a global PV network. We have invested heavily in IT systems to work with cutting edge technologies in order to minimize unnecessary workload and optimize our procedures. All safety and regulatory systems are installed in-house at Pharmathen s data centers. In addition, our group of experts is acting as the nominated Local Pharmacovigilance Contact for a number of top multinational pharmas. ICSRs (in 1000s) 20 Reporting compliance % ICSRs closing 2012 closing 2013 closing 2014 closing 2015 closing % PSURs/ACOs Pharmathen Services 16

17 Our Services Our team can provide assistance with the following: System Development & Standalone Services PV System Pharmathen offer a full range of core pharmacovigilance services customized to your needs, providing end-to-end coverage for your product portfolio. QMS Either be it from writing or reviewing your SOPs, to supporting you during an inspection or run a mock audit for you, to training and consultancy, we can fully cover you to achieve compliance and increase productivity. Risk monitoring & management Pharmathen offer a wide range of signal detection services including classical ad hoc clinical evaluation of case reports and/or statistical analysis to detect abnormal reporting frequency fluctuations throughout vast datasets of case reports. We can also undertake Emergency Communications and trigger Risk escalation/resolution processes. Local PV Network & EU QPPV Pharmathen can act as your local PV liaison with Authorities in all EU regions or even assume the EU QPPV responsibility for your products. Our Local PV Services include: Local contact person availability and back-up system, local legislation monitoring, local non-indexed literature screening, case collection & follow-up, NCA inspection readiness/support. Operations & Technical Competency Case management Pharmathen are hosting on premises an E2B compliant fully validated database with gateway transactions for end-to-end processing of case reports. Alternatively, we can conduct case management remotely connecting to your technical resources or using EVWeb. IT infrastructure & tools We can help you with xml data analysis, transformation, migration and uploading onto structurally E2B-compliant databases. XEVMPD We can insert and maintain your Article 57 data for your medicinal products either via EVWeb or from a gateway solution. Pharmathen Services 17

18 Medical Writing & Consultancy Operations Medical Writing Med Info Queries Business Intelligence, drug repurposing Safety Monitoring of Clinical Trials, Cosmetovigilance, Materiovigilance We produce high quality scientific documentation throughout the lifecycle of a medicinal product at all regulatory phases (Clinical or Non-clinical Overview, compilation and implementation of RMPs, PI-CCSI, readability test support etc). We can file, triage, respond and reconcile medical enquiries related to your product. We employ combined resources to achieve strategic consultancy and business development support on decision making based on the safety profiles of the products. We combine Pharmacovigilance, Pharmacoepidemiology and Pharmacogenetics to critically reevaluate data in order to achieve protection of public health, assure corporate regulatory compliance, improve current therapies and address unmet medical needs. Our range of services is extended to include review of clinical and non-clinical study protocols, investigator brochures, and final study reports with end-to-end analysis of safety-related data from clinical trials and post authorization studies; post-hoc scientific and statistical analysis of safety data; preparation and application for the WHO Prequalification Program; complete implementation of a Cosmetovigilance / Materiovigilance system; and more. Pharmathen Services 18

19 Our ATC portfolio: Antibiotics antimycotics and antivirals Antidiabetics Antineoplastics Antiinflammatory and topical pain killers Antithrombotics Bisphosphonates Cardiovascular drugs CNS drugs Ophthalmics Pituitary & hypothalamic hormones, antiparathyroid agents Respiratory drugs Statins and fibric acid agents Topical antifungals and corticosteroids Urologicals Vitamins and minerals Drugs for alimentary disorders And others Pharmathen Services 19

20 A worldwide collection of Pharmacovigilance data in the global safety database: For more information please feel free to contact us: Τ , (ext. 9) 24/7 <10 ICSRs 10<ICSRs<50 50<ICSRs< <ICSRs< <ICSRs< <ICSRs< ICSRs Pharmathen Services 20

21 Pharmathen Services 21

22 Pharmathen Services 22 A successful preclinical and clinical development program is always a challenge in the pharmaceutical world.

23 Scientific Operations Services Pharmathen can assist you on the following: CRO selection Having a wide experience with many CROs worldwide and also a huge experience on Clinical Trial Application process and timelines of the regulatory environment of many counties around the world we can guide you through the process of prequalification site-audit and our experience on the local regulatory environments so as to select the CRO that fits best with your clinical development. After an initial screening of many CROs, we contact all the key persons so as to gather all the information we need for our evaluation. This way the choices are narrowed down so as to ensure that the best option is selected for our client. In the final selection there are also some additional key parameters leading to the choice of the ideal CRO such as Pre-qualification audits, Scientific background of the involved personnel, Expertise, Regulatory environment they belong to, Consistency, Cost savings, General response time, timelines, lead-time, regulatory approval time, our prior experience, etc. Monitoring Services Our skilled and well-trained clinical associates ensure the highest quality of study monitoring in all phases of Bioequivalence studies or clinical trials. More specifically, on-site monitoring visits throughout the study are conducted to: Oversee data collection Review source documentation and case report forms Ensure regulatory compliance Resolve data queries Conduct interim analyses Harmonize and ensure the high quality of deliverables. Pharmathen Services 23

24 Preclinical and Clinical design and medical writing Our highly qualified medical writing team consisting of experienced MSc and PhD level scientists can assist you in every stage of your development. More specifically we can support you on the following areas: Preclinical and Clinical study design Protocol writing Clinical reports Investigators brochure IMPD and compilation of clinical trial application documents Design and Compilation of Pediatric Investigational plans In Vivo In Vitro Correlation (IVIVC) The development and validation of an IVIVC model is an important component of dosage form development and optimization. An IVIVC model is a relationship (preferable linear) between a biological parameter (i.e., Cmax, Tmax or AUC) produced by a dosage form and an in vitro characteristic (i.e., in vitro dissolution). The development of the correlation usually involves the following three steps: 1) Develop formulations with different release rates. 2) Obtain in vitro dissolution profiles by a suitable dissolution test and in vivo plasma concentration profiles. 3) Estimate the in vivo absorption curve using appropriate deconvolution techniques (e.g., Wagner-Nelson model, numerical techniques). Pharmathen Services 24

25 There are four IVIVC categories including Level A, Level B, Level C and multiple Level C. The highest level correlation, Level A, is a direct point-to-point relationship between the amount of the drug dissolved (in vitro data) and the amount of the drug absorbed (in vivo data). In other words, a Level A IVIVC model should predict the entire in vivo time course from the in vitro data. In a Level B IVIVC, the mean in vitro dissolution time is compared either to the mean residence time or to the mean in vivo dissolution time. A Level C IVIVC establishes a single point relationship between a dissolution parameter (e.g., percent dissolved at a specific time point) and a pharmacokinetic parameter (e.g., Cmax, Tmax, AUC) while a multiple Level C IVIVC correlates one of several pharmacokinetic parameters of interest to the amount of drug dissolved at several time points of the dissolution profile. An IVIVC model can be very useful for the comparison of therapeutic performances of two medicinal products containing the same active substance. A validated IVIVC can be used as a surrogate for in vivo bioavailability studies, and thus the number of bioequivalence studies required for approval as well as during scale-up and post approval change can be minimized. Pharmathen develops and applies IVIVC models using the following software packages: Microsoft Excel MATLAB Winnonlin The application area concerns: Optimization of the product development procedure (e.g., highly demanding products, sustained release formulations) Optimization of the pivotal BE studies designs (i.e., repeated dose studies) Support post-approval changes (i.e., modifications affecting dissolution rates) Pharmathen Services 25

26 Intellectual Property Services The Pharmathen patent department is well known in the industry for providing excellent patent reports for the projects that we out license to our customers. These freedom-to-operate reports are comprehensive, clear and updated regularly. We also engage top class scientific advisors and we can provide experimental reports in order to back up our positions. Pharmathen also files and prosecutes globally an extensive number of patents. All this work, searching, analysis, drafting, patent prosecution is performed by our internal patent team. Pharmathen Services 26

27 For the first time we are offering our patent services to external companies. We can offer the following services: 1. Freedom to operate reports. Comprehensive reviews of all patents (including status checks) relevant to the INN or it can be tailored to your need synthesis, intermediates, formulation, physical chemistry, use claims etc. The reports can be provided alone or with a review of your product. 2. Patent drafting. We can offer a full range of services from drafting to filing, prosecution and renewal in any life science field. 3. Strategy. We appreciate that any external patent attorney can offer analysis of a patent claim, but do they offer solutions? We know how to deliver products that are balanced in terms of commercial viability, timing and minimize uncertainty. Patent Team The patent team has eight people and is based in the UK, Athens and Thessaloniki. We are all science graduates with a range of disciplines from Chemistry, Pharmacy, Biochemistry and Molecular Biology. We operate in English but members of our team speak Greek, French, German and Chinese. Why work with Pharmathen? Tired of your outside patent attorney sending large bills and not providing clear commercially relevant advice? We appreciate that we operate as a division of Pharmathen, but we will operate on a strict confidentiality basis. To discuss further please contact: Apostolos Aivaliotis - aaivaliotis@pharmathen.com and Pharmathen Services 27

28 Pharmathen Services 28 Quality Management Quality Assurance Proposed Services

29 Corporate Quality Management Providing compliance with national and international standards and legislation. Providing compliance with internal procedures. Schedule, performance, support and report on internal audits in order to verify that the site operational management systems comply with the requirements of current GMP, ISO 9001 and ISO standard. Development of the master documents SOPs and Protocols of the Organization s QMS concerning the main quality affairs processes ( change control, customer complaints, corrective preventive actions, risk management, deviation investigation reports, suppliers complaints, Vendors qualification, Personnel Training, Annual quality product reviews, hygiene rules as defined in Pharmaceutical legislation ). Quality Assurance Development of the master documents SOPs and Protocols concerning the performance and reporting on Process Validation, Cleaning Validation, Product Quality Results Review and generally other validation activities. Development of the master documents SOPs and Protocols concerning the Environmental controls- Water treating systems - Process Validation & Product Quality Results Review of commercial batches. Development of the master documents SOPs and Protocols concerning the executing, monitoring and reporting on DQ / IQ / OQ / PQ / Calibrations for machinery & production areas. Product Quality Operations Liaison support between client s company (Pharmaceutical) and third party subcontractors to ensure compliance to Regulatory requirements, industry standards (GMP) and client company s expectations. Development of Quality / Technical Agreements between Pharmathen and third party manufacturers (TPM) as well as between Pharmathen and clients and/or clients affiliates. Coordination and collaboration in all quality aspects concerning new product technology transfers between development site and commercialization site within organization and between organization and third party manufacturers (TPM). Support new product introductions at the TPM sites and cooperate in the introduction of new analytical methods to pace with times and new regulations requirements. Pharmathen Services 29

30 Quality Control Services cgmp Quality Control (QC) testing for excipients, intermediates, raw materials, APIs and GMP batch release testing for drug products supporting pharmaceutical development and manufacturing. Pharmathen provides GMP quality control analysis and offers technical advice on the most cost effective approaches to QC testing for GMP manufacture of pharmaceuticals.quality control analysis, GMP microbiology release testing and GMP batch release testing is a routine activity in our network of GMP analytical laboratories which have a lot of experience for drug products. Pharmathen provides a full range of pharmacopoeial testing. If existing pharmacopoeial (compendial) methods are not appropriate, Pharmathen can provide method transfer for our client s methods covering a wide analytical technology scope from HPLC, GC, FTIR, and more. Expertise includes solids, semi-solids, lyophilized powders, liquids, parenterals etc. Compendial analysis for Excipients and Raw Materials Analysis (USP, EP and JP) Client specific method Intermediates & Finished Product Testing GMP batch Release Testing ICH Stability Testing & Storage Microbiological quality of sterile and non sterile products Pharmathen Services 30

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32 Pharmathen S.A., Headquarters 44, Kifissias Avenue, Marousi, Athens-Greece T: , F: Pharmathen UK Ground Floor South Wing, 10 Bricket Road, St Albans AL1 3JX, United Kingdom T: +44 (0)