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Pharmathen | Services | 2
PhilosophyWe embrace research and science,providing innovative products and integrated services to improvepeople’s quality of life.
Our DNA
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.
MissionWe 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.
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Table of Contents
4 Company Profile
6 Third Party Auditing
10 Regulatory Affairs
14 Drug Safety, Medical
& Risk Assessment Services
22 Scientific Operations
26 Intellectual Property
28 Quality Management & Assurance
30 Quality Control
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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.
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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”
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.
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 325 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.
Contacts:
For details and inquiries, please contact our Head of International Audits & Compliance via e-mail (madhu@pharmathen.com) or by phoning 0091-98401-71659 or 0030-6943-298600
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.
Total 13 – 14 ‘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
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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 325 audits• Total ‘hands-on’ industrial experience of 85 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
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Pharmathen’s Regulatory Affairs Department has more than 20 years of experience in regulatory submissions worldwide. Our department consists of more than 25 highly qualified professionals in the fields of biology, chemistry, molecular genetics, medicine and pharmacology/toxicology.
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
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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
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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 Ioanna Manteli – imanteli@pharmathen.com
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Strategy
Adoption
PlanningOperation
DynamicImprovement Development
Excellence
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Pharmacovigilance Pharmacovigilance (PV or PhV), also known as Drug Safety, is the pharmacological science relating to the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products.
PharmacoepidimiologyPharmacoepidemiology is the study of the uses and effects of drugs in well defined populations. To accomplish this study, pharmacoepidemiology borrows from both pharmacology and epidemiology.
PharmacogeneticsPharmacogenetics is the study of genetic differences in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.
We, at Pharmathen, aiming to comply with the continuously changing and demanding legislative environment, have employed a unique tool, the 3-P Science Model, which combines Pharmacovigilance,Pharmacoepidemiology andPharmacogenetics to achieve protection of public health, assure corporate regulatory compliance, improve current therapies and address unmet medical needs.
A wide spectrum of expertise from clinical pharmacology, epidemiology, pharmacy and neuroscience to applied and clinical biochemistry, molecular biology, international health policy and quality compliance are available for the 3-P performance.
3-P
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Pharmacovigilance Services
Centralized approachPharmathen offer a full range of pharmacovigilance services customized to your needs. If you want to avoid the burden of setting up your own pharmacovigilance system, Pharmathen may be a flexible and trustworthy solution providing end-to-end coverage for your product portfolio. Alternatively, we can set up your global pharmacovigilance system, write SOPs, train your staff and host the global safety database on your behalf.
Functional approachPharmathen can support you with specific functions i.e. worldwide literature search, aggregate report writing, case processing, global safety database management, signal detection, XEVMPD and local PV Contact Person support.
The Pharmathen key benefits
• in depth knowledge of changing regulations and legislation• extensive background in the field• track record of quality and efficient outputs• capacity for large volumes of work• effective project management• inspection ready team (already inspected by regulatory agencies)• established network of partnerships• investment in IT systems• client oriented approach
Pre- Clinicalstudies
Clinical Trials
Drug Submission
LisenseEarly Post-market Period
Increasing
Re-evaluationof licenseand commitments
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Pharmacovigilance within Pharmaceutical Product Life Cycle
• Qualified Person for Pharmacovigilance QPPV Services• Safety Aggregate reporting & Analytics• Quality Management
• Clinical Trial & Post Marketing Case Management
• Literature Monitoring
• Medical Information• Post Marketing Case Management• Signal Detection & Benefit-Risk Management• Audit Support
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Pharmacovigilance datais the basisof the 3-P Model
Pharmathen monitors more than 200 active substances. Our weekly Medical & Clinical literature screening, the continuous risk/benefit evaluation and medical information functions are of outmost importance for data collection and their scientific assessment. Identified off-label uses or even ADRs may lead to new therapies for unmet medical needs or to drug repositioning and improvement of existing therapies.
Pharmacovigilance
Pharmacoepidemiology
Pharmacogenetics
Maximize Safety
Maximize Efficacy
Maximize Market Potential
Save Money
Save Time
Drug Rescue
Drug Repositioning
Drug Discovery
Indication Discovery
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3-P Model: An open source approach aiming to improve existing therapies/ identify treatments for unmet medical needs
Improved safety and/or efficacy Profile
New Therapies
Drug Interaction/Genetic Profiling
Epidemiological Assessment
Alternate PharmacologicalApplication
Substance Biochemical/Metabolic mapping
Disease Mechanism Identification
Current treatment & intervention assessment/ evaluation
Active Substance/Moiety
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The Pharmathen Drug Safety, Medical and Risk Assessment Services presence in Europe
For more information please feel free to contact us:
Mrs. Evangelia DovaSafety Agreements Supervisor / Deputy QPPVT +30 210 6604423E edova@pharmathen.compharmacovigilance@pharmathen.com
A successful preclinical and clinical development program is always a challenge in the pharmaceutical world. In Pharmathen Scientific Operations Department we know how to ensure this, from the very early stages of a development.
More specifically, Pharmathen can assist you on the following:
CRO selectionHaving 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.
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
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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).
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.
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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)
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.
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 minimise uncertainty.
Patent Team
The patent department is led by Andrew Brown who is a fully qualified UK and European patent attorney with over 20 years’ experience in life sciences, having worked for a number of companies; GlaxoWellcome, AstraZeneca, ReckittBenckiser, Barr, PLIVA and Teva. The patent team has nine people and is based in theUK, 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:
Andrew Brown – abrown@pharmathen.com and +441612983111
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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 14001 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.
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 technologyscope 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
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Pharmathen S.A., Headquarters44, Kifissias Avenue, 151 25 Maroussi, Athens-GreeceT: +30 210 66 04 300F: +30 210 66 66 749
Pharmathen UKPrincess Mary House4 Bluecoats Avenue,Hertford, HertfordshireSG14 1 PB, United KingdomT: +44 (0) 1992 532280F: +44 (0) 1992 509203
info@pharmathen.com www.pharmathen.com
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