Department of Pharmaceutical Chemistry

Pharmaceutical and Medicinal Chemistry Research Group

QUALITY MANUAL

2007

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

University of Kuopio Department of Pharmaceutical Chemistry Pharmaceutical and Medicinal Chemistry research group (PMC research group)

QUALITY MANUAL Summary of the Finnish version

___________________________________________________________________________ Author: Kirsi Luoto Maintenance and updating: Krista Laine Page 1/16 Printed on:___.___.____/___ Copied on:___.___.____/___

Version 8

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Contents

Page

1. PMC research group 1.1 Scope and research areas 1.2 Main processes 1.2.1 Research 1.2.2 Cooperation research 1.2.3 Teaching 1.2.3.1 Graduate studies 1.2.3.2 Postgraduate studies 1.3 Values and ethics 1.4 Vision 1.5 Strategy 1.6 Measurement of activities 1.7 Laboratory facilities 1.8 Data management and security

3 3 4 4 4 4 4 4 7 7 7 8 8 8

2. Personnel 2.1 Personnel policy 2.2 Organisation 2.3 Responsibilities 2.4 Training and development 2.5 Introduction 2.6 Job description 2.7 Work safety

8 9 9 10 11 11 11 12

3. Quality management system 3.1 Quality policy 3.1.1 Quality levels 3.1.1.1 Academic research 3.1.1.2 Cooperative research 3.1.1.3 Laboratory work of students 3.2 Purpose of the quality system 3.3 Responsibilities 3.4 Structure of the quality management system 3.4.1 Quality manual 3.4.2 Standard operation procedures (SOPs) 3.4.3 Process flow charts 3.5 Developing and measurement 3.5.1 Audits 3.6 Quality assurance 3.7 Documentation 3.8 Deviations

12 12 12 12 13 13 13 13 13 14 15 15 15 15 16 16 16

________________________________________________________________________________ Page 2/16

Version 8

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

1. PMC research group The Pharmaceutical and Medicinal Chemistry (PMC) research group is a part of the Department of Pharmaceutical Chemistry the Faculty of Pharmacy, at the University of Kuopio (http://www.uku.fi/english, http://www.uku.fi/farmasia/fake/indexe.htm). The PMC research group is a part of the Drug Research and Development Centre’s laboratories (Drug Design and Synthesis, Structural Chemistry and Drug Analysis). The Drug Research and Development Centre increases collaboration between the drug research groups at the University of Kuopio and pharmaceutical companies in order to create and transfer new products and technologies to the private sector (http://www.uku.fi/flk/indexe.htm). 1.1 Scope and Research Areas The core areas of the PMC research group are medicinal chemistry and the development of pharmaceutical drugs. The PMC research group conducts research and teaching on an internationally high level. The research is published in the high quality journals and the pharmaceutical innovations of the group are patented. The group performs collaboration projects with international and national pharmaceutical industry and universities. The research performed in PMC research group can be divided in 5 main research areas. The research areas of the PMC research group are presented in Table 1. Table 1. The 5 main research areas of the PMC research group Prodrug Technology

Drug Analysis

Molecular Modelling

Cyclodextrin Technology

Drug Synthesis

Prodrugs

Analysis of organic compounds (drugs, metabolites, endogenic compounds, etc.)

3D-QSAR

Sublingual administration

Synthesis of enzyme inhibitors and receptor ligands

CNS drug delivery Physicochemical characterisation of (pro)drugs

In situ- and in vivo -animal models

In vitro-

permeation: - Ocular - Topical (skin)

Method development, validation and documentation Instrumentation: - HPLC, UV/ DAD/FD/EC - GC-MS/LC-MS - spektroscopy

Target based drug design Method development of molecular modelling Virtual screening Modelling of physicochemical characteristics of drugs and adjuvants

Pulmonar administration Complexation of peptides Amorphic natural cyclodextrins Analysis of cyclodextrins

Synthesis of prodrugs Structure research: - elemental (CHN)-analysis - NMRspectroscopy - Mass spectrometry

________________________________________________________________________________ Page 3/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

1.2 Main processes

1.2.1 Research The research carried out in the PMC research group is presented on the www-pages of the Department of Pharmaceutical Chemistry (http://www.uku.fi/farmasia/fake/pmcresearch.htm). Each research project has its own study and research plans as well as a financial plan. To ensure the traceability of the study, every step of the study and results of the study are documented. All documents of importance for the research are archived. The scientists of the research group keep up their expertise by educating themselves through international courses and conferences and by following international publications. The opportunities for patenting results are systematically clarified before the results are published. The scientists of the research group are encouraged to cooperate with the private sector and to patent the results of their studies.

1.2.2 Cooperation research The cooperation research with the international and national pharmaceutical industry and universities is one of the main objectives of the PMC research group. The needs and requirements of the collaborators are discussed beforehand and performed according to the agreed principles. Also the regulations and instructions of the University of Kuopio are followed. The cooperation research is continuously developed according the needs of collaborators.

1.2.3 Teaching 1.2.3.1 Graduate studies

The scientist of the PMC research group takes part in the teaching of the Department of Pharmaceutical Chemistry. The Department provides teaching to students whose degree will be Bachelor of Pharmacy, Master of Pharmacy or Master of Science in Medicinal Chemistry. The field of the teaching is medicinal and pharmaceutical chemistry (analytical and synthetic pharmaceutical chemistry, synthetic, organic and bioinformatics, pharmaceutical biology, biochemistry, biotechnology, drug design and related topics). The teaching provided by the Department of the Pharmaceutical Chemistry is presented on the department’s www-pages (http://www.uku.fi/farmasia/fake/english/studies.htm). The structure of the degrees of Bachelor of Pharmacy, Master of Pharmacy and Master of Science in Medicinal Chemistry is shown in the University of Kuopio student’s guide of pharmacy (http://www.uku.fi/opiskelu/farmasia_opas.pdf, note: in Finnish). The quality manual of the teaching at the Department of the Pharmaceutical Chemistry is presented on the web site http://www.uku.fi/farmasia/fake/opetuksen_laatu.shtml, note: in Finnish.

1.2.3.2 Postgraduate studies

One of the main areas of the PMC research group is the postgraduate studies of the Ph.D. students. The PMC research group provides teaching to the Ph.D. students in its research areas. ___________________________________________________________________________ Page 4/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

The teaching is based on the scientific research and the latest knowledge in the field of pharmaceutical and medicinal science. The Ph.D. students of the group have graduate school places in the Graduate School of Pharmacy, the Graduate School of Bioorganic and Medicinal Chemistry and The National Graduate School of Informational and Structural Biology and Drug Discovery Graduate School. The Ph.D. dissertations of the PMC research group are presented in Table 2. The instructions for the postgraduate studies at the Faculty of Pharmacy are shown on the internet: http://www.uku.fi/farmasia/jatkokoulutus.shtml (note: in Finnish). The general instructions for the postgraduate studies at the University of Kuopio are on the web site http://www.uku.fi/opiskelu/farmasia_jatko_opas.pdf (note: in Finnish).

___________________________________________________________________________ Page 5/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

Table 2. The Ph.D. dissertations of the PMC research group Year

Dissertation

Tomi Järvinen

1992

Improvement of the Physicochemical Properties and Chemical Kinetics of Pilocarpine by Prodrug Technique

James Callaway

1994

Pinoline and other Tryptamine Derivatives: Formations and Functions

Antti Poso

1995

Modeling of some Bioactive Compounds Utilizing CoMFA with Different Field Types

Cecil Navajas Polo

1996

Computer-Aided Molecular Design Applied to Different Biologically Active Compounds

Pekka Jarho

1997

Cyclodextrins in Eyedrop Formulations: Studies with Pilocarpine Prodrugs, Anandamide and Dipivefrine

Paula SaarinenSavolainen

1998

Evaluation of In Vitro Methods Used to Study Interactions of Ophthalmic Drugs and Pharmaceutical Excipients with Lipid Bilayers and Cellular Membranes

David W. Pate

1998

Anandamide Structure-Activity Relationships and Mechanisms of Action on Intraocular Pressure in the Normotensive Rabbit Model

Jouko Savolainen

2000

Improvement of the Physicochemical Properties and Oral Bioavailability of Poorly Bioavailable Drugs by Cyclodextrin- and Prodrug-Technology

Jarkko Rautio

2000

Synthesis and In Vitro Evaluation of Novel Naproxen and Ketoprofen Prodrugs for Topical Drug Delivery

Jari Kovalainen

2000

Intramolecular Hydrogen Bonding in Histamine H3-Receptor Activation: Synthesis, NMR Studies and SAR of a Series of H3-Receptor Ligands

Riku Niemi

2000

Bisphosphonate Prodrugs - Synthesis and In Vitro Evaluation of Novel Clodronic and Etidronic Acid Derivatives

Jukka Leppänen

2002

Design and Synthesis of Entacapone Prodrugs and L-Dopa-Entacapone Codrugs

Erik Wallén

2003

Design and Synthesis of Novel Prolyl Oligopeptidase Inhibitors

Antti Mäntylä

2004

Synthesis and In Vitro Evaluation of Novel Buparvaquone Prodrugs for the Treatment of Leishmaniasis

Krista Laine

2004

Intraocular Pressure Lowering Activities of Endogenous Cannabinoids, and Their Uptake and Enzyme Hydrolysis Inhibitors in Normotensive Rabbits

Anu Tervo

2005

Molecular Field-Based Activity Predictions and Virtual Screening in Computer-Aided Drug Design

Juha Juntunen

2005

Water-Soluble Prodrugs of Cannabinoids

Outi Salo

2006

Molecular Modeling of the Endogenous Cannabinoid System: Usability of Modeling Results in Drug Design

Jukka Holappa

2006

Design, Synthesis and Characterization of Novel Water-Soluble Chitosan Derivatives

___________________________________________________________________________ Page 6/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

Year

Dissertation

Susanna Saario

2006

Enzymatic Hydrolysis of the Endocannabinoid 2-Arachidonoylglycerol. Characterization and Inhibition in Rat Brain Membranes and Homogenates.

Teija Parkkari

2006

Synthesis of Novel Cannabinoid CB1 Receptor Ligands.

Elina Jarho

2007

Synthesis, Structure-Activity Relationships and Physico-Chemical Properties of Novel Prolyl Oligopeptidase Inhibitors.

Janne Mannila

2007

Cyclodextrins in Intraoral Delivery of ∆9-tetrahydrocannabinol and Cannabidiol.

1.3 Values and ethics The PMC research group is committed to good scientific research and a continuous development of the research. The scientific efficiency of research on society is recognised. The basic values of the research group are expertise, responsibility, innovativeness, courage and consideration of the ethical values. The development of the group and its research is systematic, based on cooperation, and trust and respect on fellow workers. The PMC research group performs high level, confidential and effective research both within the research group and with the outside collaborators. The research follows high scientific standards and the ethical principles of the Finnish scientific society. 1.4 Vision The aim of the PMC research group is to be a high level international research group which • gives high quality teaching in its field of research both to graduate and postgraduate students • performs high quality, internationally-recognised and interdisciplinary scientific research • makes from one to two patentable drug innovations per year and promotes the commercialization of innovations • carries out high quality cooperation projects with the national and international pharmaceutical industry and other universities • provides high quality education in the pharmaceutical chemistry as well as a nationally unique education in the medicinal chemistry • takes part in international research projects • promotes the regional competitiveness of Eastern Finland

1.5 Strategy The main strategies of the PMC research group are to • publish the results in the high quality international-recognised publications • aim at interdisciplinary and wide cooperation • maintain high quality in the research • clarify the opportunities to patent the discoveries prior to the publishing • enlarge new research areas • organise opportunities for post-doc visits of students • increase cooperation with the private sector of pharmaceutical industry • develop the Drug Research and Development Centre

___________________________________________________________________________ Page 7/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

• • • • • • • •

Version 8

support the education of the group’s personnel develop active cooperation projects with the international research groups increase the efficiency of students recruitment by actively informing about the research areas and results of the group keep up to date the teaching of the group based on the development of research areas develop the shared teaching programme with the medicinal chemistry and increase its reputation develop the quality management system increase the efficiency of external funding applications by extending the responsibility of funding applications to wider personnel participate actively in several graduate schools

1.6 Measurement of activities The indicators of activities at the PMC research group are 1. The level of Impact Factor (IF)-publications (outstanding, excellent or other good level or a new type of journal which has not yet been classified) 2. The number of IF-publications and the sum of IF-publications 3. The number of Ph.D. degrees 4. The number of degrees of Bachelor of Pharmacy, Master of Pharmacy and Master of Science in Medicinal Chemistry 5. The number of patents / patent applications 6. The number of post doc visits 7. The amount of external funding 8. The number of group members (IF = Impact Factor, how often is the publication been cited in scientific publications in one year period). The indicators are followed at least once a year. The results are discussed and actions determined with the group’s personnel within seminars of the PMC research group. 1.7 Laboratory facilities The facilities of the PMC research group are in the Canthia and Mediteknia buildings at the University of Kuopio. The PMC research group has all necessary equipments for the studies and new equipments are acquired as needed. 1.8 Data management and security The data management and security issues of the PMC research group follow the rules and regulation of the University of Kuopio (http://www.uku.fi/tike/, http://www.uku.fi/atkk/tietoturva/, note: in Finnish). The research group has an internal file server (Samba), which for example enables file sharing and systematic and regular backup of all electronic documents of the research group. The internal file server is taken care of by the group’s security management. 2. PERSONNEL The personnel of the PMC research group is the key to the success of the group. The strengths of the group are based on the multidisciplinary expertise of the personnel. The PMC research group ___________________________________________________________________________ Page 8/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

includes teachers, scientists, postgraduate students, technical assistants and graduate students. The main part of the personnel (> 70 %) is employed by external funding. 2.1 Personnel policy The personnel policy of the PMC research group is based on fairness, open communication, discussions and cooperation of the personnel. The high quality and effectiveness of the group’s scientific research and teaching are attained by the expertise and responsibility of personnel, encouraging working atmosphere and consideration of ethical values. 2.2 Organisation The organisation chart of the PMC research group is presented in Figure 1.

___________________________________________________________________________ Page 9/16

Version 8

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

University of Kuopio

Faculty of Pharmacy

Department of Pharmaceutical Chemistry

Drug Research and Development Centre

Pharmaceutical and Medicinal Chemistry Research Group

Group Leader

Quality Assurance

Post doc- Group

Drug Design / Drug Design and Synthesis Laboratory

Drug Synthesis and Structural Chemistry / Drug Design and Synthesis Laboratory

Pharmaceutical Research / Drug Analysis Laboratory

Research Areas Prodrug Technology

Drug Analysis

Molecular Modelling

Cyclodextrin Technology

Drug Synthesis

Research Projects Project 1

Project 2

Project 3

Project 4

Project 5

Project n

Figure 1. The organisation chart of the PMC research group.

2.3 Responsibilities Post doc-Group: • non-scientific • discuss about research ideas ___________________________________________________________________________ Page 10/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

• • •

•

Version 8

discusses about funding strategy and responsibilities discusses about postgraduate studies of the Ph.D consists of o Group Leader o Post docs of the group o Quality Assurance Person o Representative of the Ph.D. students (when needed) o Representative of the technical assistance (when needed) assembles at least twice a year

The persons in charge of the research laboratories: • guide the workload of technical assistants • plan the usage of laboratory facilities and equipments • are responsible for acquiring of small equipments • arrange regular meetings of laboratories The persons in charge of the research areas: • are leaders of main research areas • manage the personnel of particular research area • are responsible for comprehensive development of research area • are responsible for practical issues The persons in charge of the projects: • are responsible for achievement of the aims of the projects • are responsible for the regular meetings of the projects • are responsible for cooperation projects • are responsible for reporting 2.4 Training and development The personnel of the PMC research group have a right and a duty to improve their own expertise by continuous education. The personnel inform the management of their need for suitable education and the opportunities for it. The training programmes are planned together with the management. The education of the personnel is documented for example in the CV, a training plan and / or a training card. The need for the development in the work is mapped out in the discussions with the management and by a personnel questionnaire. The questionnaire for the personnel is filled out at least every second year. The results of the questionnaire are discussed and actions are decided with the personnel in the group seminars. The PMC research group seminars are held at least twice a year. 2.5 Introduction All new employees are introduced to the activities of the PMC research group and the University of Kuopio by following the standard operating procedure of the group. The introduction of the personnel is documented. New employees are introduced to the general procedures of the research group and to the specific procedures that they need in their work. 2.6 Job description The PMC research group has standard operating procedures for the job descriptions, training and responsibilities of the personnel. Specific job descriptions, training programmes and responsibilities ___________________________________________________________________________ Page 11/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

of the personnel are documented as and when needed (for example in the cooperation research projects). 2.7 Work safety The PMC research group has standard operating procedures for the work safety. The person responsible for the work safety trains all new personnel to the work safety, the laboratory regulations and the first aid directions of the group and ones of the University of Kuopio. 3. QUALITY MANAGEMENT SYSTEM The basic elements of the quality management system in the PMC research group are the commitment of the personnel to the continuous development of the system and the contentment of the collaborators to the activities of the group. The issues of quality management system are informed to the personnel by e-mail, in the laboratory meetings and other meetings or seminars of the group. 3.1 Quality policy The PMC research group is innovative, appreciated research group which research is scientifically at the high level and internationally well known. The activities of the group are efficient, open, flexible, encourage and custom oriented. The activities are continuously developed to respond the internal and external challenges. The aim of the quality management system of PMC research group is to guarantee that the activities of the group responses to the internal and external needs. The quality system supports the research of the PMC group and is a part of the research practises of the group. The quality of the activities of the PMC research group is based on the personnel's skills, commitment, motivation and cooperation as well as the continuous development of all these areas. The quality management system improves the competitiveness of the research, the skills and productiveness of the PMC research group and supports the increasing cooperation in research. The quality managements system of the PMC group is developed in cooperation with the management and personnel. The aim of the quality system is to create and maintain the systematic and traceable documentation of all phases of the research. The quality policy of PMC research group is based on the quality policy of the University of Kuopio, and the Faculty of Pharmacy.

3.1.1 Quality levels The quality work of the PMC research group is performed on the level, which best serves the purpose. The quality work of the group has been categorised into three levels: academic research, cooperative research and student laboratory work.

3.1.1.1 Academic research

The academic research includes the research that has scientific publications or degrees as outcome (for example the postgraduate studies of the Ph.D. students, the research done by graduate students). The academic research follows high scientific standards and those standard ___________________________________________________________________________ Page 12/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

operation procedures of the group (SOP’s of general issues, personnel, research, methods and equipment) that are relevant for the research. The main goal of the quality work in the academic research is to ensure the validity, traceability and documentation of the research.

3.1.1.2 Cooperative research

The cooperative research follows the high scientific quality based on the expertise and general quality management system of the PMC research group. For example, the cooperative quality level is included to all of the cooperative researches of the Drug Analysis Laboratory. The level of the quality in cooperative research is instructed more specifically and accurately than in the academic research. The level of the quality is developed according to the needs and requirements of the collaborators (i.e., validations and quality assurance). If, for example, the equipment is used for the cooperative research, all users follow the higher quality level instructions when using the equipment.

3.1.1.3 Laboratory work of the students

The laboratory work of the students includes all teaching performed in the facilities of the PMC research group by a graduate student. The students are introduced to those operating procedures of methods and equipments that are needed in their work. They register as users of methods and equipment on the registration form of students and follow the procedures during their work. 3.2 Purpose of the quality system The purpose of the quality system is to • ensure the reliability and traceability of the research • maintain and continuously develop the systematic quality and documentation system • increase contentment of the collaborators and the operation of cooperation projects • promote the high quality of the research • improve the efficiency and productiveness of the activities in the group • follow and improve the achievement of aims of the group • support the development of personnel • assist the management in developing the activities 3.3 Responsibilities The personnel and the management of the PMC research group are responsible for the maintenance and development of the quality system. The management is responsible for setting the aims and arranging the resources for the quality work. The management leads, supervises and develops the quality system together with the quality assurance management. The quality assurance management has the main responsibility for the quality management system; its establishment, implementation, maintenance and development. 3.4 Structure of the quality management system The structure of the quality management system of the PMC research group is presented in Figure 2.

___________________________________________________________________________ Page 13/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

Quality Manual Process Flow Charts General Procedures

Personnel Procedures Research Procedures

Method Procedures

Equipment Procedures

Figure 2. The structure of the quality management system of the PMC research group. The quality management system consists of a quality manual, process flow charts and standard operation procedures (SOP). The quality manual and SOPs are available to the personnel as paper versions in the laboratories and as an electronic version on the internal file server (Samba) of the group. The quality system is regularly evaluated by internal audits (both by the research group and by the internal audits of the University of Kuopio). The audits by the collaborators are performed as and needed (for example in the cooperation research projects).

3.4.1 Quality manual The quality manual is the description of the activities in the PMC research group. It describes the general principles of operations and the quality system of the group. The quality manual is established and maintained by the quality assurance persons together with the management of the group. The quality manual is checked by the responsible persons of the research areas, quality checked by the quality assurance person and approved by the group leader. The quality manual is evaluated every other year and after any changes in the activities that influence the manual. The appendices of the quality manual can be changed separately to the manual. All changes of the quality manual are informed to the personnel (for example by e-mail or in the laboratory meetings). After the new version of the quality manual is available, the old version is archived. The quality assurance person is responsible for the evaluation and archiving of the quality manual. The quality manual is printed from the internal file server of the research group. After the quality manual has been printed, the person marks printing date and initials to first page of the manual. If the printed and marked quality manual is copied, the person marks the copying date and initials on first page of the manual. When the appendices are printed or copied the person marks printing or copying date and initials on each and every page of the appendices.

___________________________________________________________________________ Page 14/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

3.4.2 Standard operation procedures (SOPs) The standard operation procedures (SOPs) conduct and standardise the activities and operations of the PMC research group. The purpose of the standard operating procedures is to ensure that all operations are well planned and tested, and that the operation is always performed at same manners independently regardless the operator or the time when the operation is performed. Also the step by step traceability of the operations is ensured. The quality system of the research group is guided and controlled by the standard operation procedures (SOPs). The general standard operation procedures conduct the general operations (for example, the formulation of procedures and registers, maintenance of the documents and archiving). The research procedures conduct, for example, the use of laboratory notebooks, work safety, the rules of laboratory work, and the maintenance of the equipment. The personnel procedures guide the introduction, responsibilities, job descriptions and training of the personnel. The method procedures are instructions for performing an experiment. The procedures of the equipment guide the use and maintenance of the equipment. The SOPs can be written in Finnish or English or in both languages depending on the need.

3.4.3 Process flow charts The main processes of the PMC research group are research, cooperation research and education. The supportive processes are the quality system processes: maintenance processes and development of the quality system, new SOP, new SOP-version, removal of SOP, archiving, auditing, and introduction and training of the personnel. The processes are presented as flow charts. 3.5 Developing and measurement The quality system of the PMC research group is developed by - internal audits - feedback from personnel - feedback from collaborators - discussions in the meetings or seminars The operation of the quality system is evaluated by the personnel questionnaire. The questionnaire is collected at least every second year. It includes topics of the quality work, its maintenance and development. The results of the questionnaire are discussed and actions decided with the personnel in the group seminars. The quality system is developed according to the results of the questionnaire.

3.5.1 Audits The operation of the quality system is followed and developed by the results of the internal audits. The audits are planned beforehand and performed regularly. All results are documented and informed to the personnel. The PMC research group has standard operating procedures for performing the internal audits. The external audits (for example cooperation research projects) are planned, performed and documented case by case with the collaborators.

___________________________________________________________________________ Page 15/16

University of Kuopio Pharmaceutical and Medicinal Chemistry research group

Version 8

3.6 Quality assurance In general, the quality assurance includes the internal and external audits and their results and reports, discussion and decisions of the personnel and the maintenance of the SOP’s and the quality manual. When the quality is required to be on a higher level (for example, in the cooperation research projects), a more specific and accurate quality assurance programme is involved. In practice, the quality assurance includes testing of the systems, method validations, blanc, control and standard solutions, maintenance and calibration of the equipment. The level of quality assurance is determined to service the purpose and requirements of the research concerned. The responsible person of the research is also responsible for the practical quality assurance issues of the research. 3.7 Documentation The documentation is the most important factor in the assurance of the research traceability. The documentation of the research in the PMC research group is performed by documenting the important phases of the life span of the research. All important documents are archived. The scientist’s, laboratory and project notebooks are the most important methods of documentation in the group. The specifically detailed progress of the research is written on the scientist’s and laboratory notebooks. The person responsible for the research has a general responsibility on the documentation of the concerned research. The quality assurance person is responsible for the quality management documentations and their archiving. The composing, maintenance and archiving of the documents are conducted in standard operation procedures. 3.8 Deviations The principle of the work in the PMC research group is that the standard operation procedures are followed. All deviations from the standard operation procedures are documented. The documentation is done on scientist’s, laboratory and / or project notebooks, the notebooks of equipment or on the specific forms for deviations. The PMC research group has standard operating procedures for the controlling of the deviations and their documentation. The responsible person of the research decides the actions that the deviation causes and informs the personnel. The deviations that affect to the personnel are informed and the action decided in laboratory meetings or the group seminars.

___________________________________________________________________________ Page 16/16