Author: Marijke Korteweg, PhD (Chem), PhD (Biochem), FIQA
Integrated Quality Management Advisor
The European Agency for the Evaluation of Medicinal Products
7 Westferry Circus, Canary Wharf, London E14 4HB, UK
Introduction
Competent authorities, responsible for the authorisation and supervision of medicinal products for human and veterinary use and the European Agency for the Evaluation of medicinal products, need to ensure consistency in methodology and criteria. The endeavour to adhere to Good Regulatory Practices is to the benefit of their customers or stakeholders, whether users of medicinal products, industry, interested parties, experts and staff. The identification of needs, the consideration of performance indicators and the comparison of cost-effective procedures will enable the development of an integrated (business/quality) management system and control of the processes to ensure harmonised Good Regulatory Practices. This is particularly important in a global context with expansion at regional level with enlargement of the European Union and increased cooperation with key regulatory partners on the world stage.
The Quality Management System at the EMEA
The European Agency for the Evaluation of Medicinal products (EMEA), established in 1995 as a major contributor to public and animal health in the European Union, initiated the implementation of Quality Management principles to the marketing authorisation of medicinal products in the European Union two years later.
The EMEA must provide a service and perform its tasks under the European Union legislation in the best possible and consistent way. The resources made available to the Agency through industry fees or contributions from the EU general budget must be used in an effective, efficient, prudent and transparent way.
In 1997, the EMEA decided to implement at the Agency a Quality Management System to satisfy all partners in the system (patients, consumers, health professionals, animal owners, Member States, European Union Institutions, industry and EMEA staff).
The EMEA QMS tailor-made model
When the QMS Project was initiated, the European Foundation for Quality Management (EFQM) model was proposed as the basis of the EMEA QMS. Experience with ISO standards and Kaizen was added and the EMEA tailor-made model was at the end of 2000 quite similar to ISO 9001:2000.
As part of the EFQM model, improvement teams were created and, upon completion of a team's project, discontinued. From 2 teams in early 1997 focussing on the EMEA culture and processes, the number increased to 9 in 1997 and 1998 and was subsequently reduced to 5 teams in 2000 and teams as needed for improvement of the processes from 2001 on (start of the integrated management system).
At the height of the work by the improvement teams about 50% of EMEA staff were involved. At the General Staff Assemblies they shared the progress of their projects with all EMEA colleagues.
The strength of the EMEA QMS is due to the fact that the staff and management have built the system together. At the EMEA the system has many "owners", all those who have spent time and effort to build, with limited resources, a system to assure the quality of the EMEA tasks.
Staff contributions to EMEA QMS
Building the system to assure the quality and improving it continuously requires enthusiasm and willingness to achieve, dedication to the task and energy and determination to hold on. It is the spirit of the multicultural staff at the EMEA and the leadership of those, who believe in building a centre of excellence, which is at the basis of the success and the following developments:
- The EMEA Mission Statement
- The EMEA Quality Policy and electronic Quality Manual
- The procedures for the EMEA Workplan, Annual Report and Sectorial Business Plans
- The EMEA Code of Conduct
- The EMEA internal audit system (14-18 audits per annum since 1998 by internal auditors, trained to audit in accordance with ISO 10011, now ISO 19011, to identify opportunities for improvement)
- Improvements in the performance evaluation, training and job description policies
- The EMEA staff motivation surveys, conducted annually since 1998
- The electronic EMEA activities tracking system "ActiTrak" to collect data for activities according to source of revenue
- Linked to ActiTrak is a system of flexible working hours
- A system to control the quality of information and translation of documents in the 11 official EU languages.
Further developments or spin-offs are:
- The EMEA Business Measurement, or EMEA scoreboard, a data measurement model incorporating many measurements obtained by earlier developed systems within the EMEA and with outside partners, a live database of EMEA key performance indicators, covering the following areas: scientific output, people, finance and strategic business planning.
- Euro-partnerships to improve relations with other EU bodies and enhancing the implementation of the Code of Conduct by EMEA staff, Management Board, Scientific Committee members and experts
- The Product Information Process Improvement Team, supporting the Product Information Management Project, including a scientific memory.
Benchmarking in the framework of the Pan-European Regulatory Forum on Pharmaceuticals
Good Regulatory Practices deserve to be a priority action area and several competent authorities had already experience with the implementation of a Quality System, whereas others wanted to benefit from the experience already gathered. Benchmarking is therefore appropriate to assure the quality of the tasks of the competent authorities in a cost-effective way and an ideal forum for this undertaking is The Pan-European Regulatory Forum (PERF). PERF is being undertaken with financial assistance from the European Community's Phare programme. The ultimate aim of this programme is the transposition of all technical regulations and European technical acts into the national legislation of central and eastern European Countries (CEECs). In this context and in the area of medicinal products, the PERF is designed to establish an internationally open dialogue, develop working mechanisms to facilitate adoption of the common technical requirements, ensure effective implementation and identify areas where additional action may be required.
Preparation of the GRP-QMS Benchmarking
To establish a benchmarking programme addressing the most important factors for the successful implementation of a quality system, a questionnaire was developed pertaining to Good Regulatory Practices (GRP) and Quality Management Systems (QMS). GRP was defined as "A Quality System to ensure that the users of medicinal products, the applicants, the regulators are satisfied with the scientific advice, opinions, the establishment of maximum residue limits, inspection and assessment reports and related documents, taking into consideration legal requirements and guidance in order to protect and promote human and animal health."
Authorities were invited by means of a questionnaire to establish for PERF II the way forward to benchmark Good Regulatory Practices-Quality Management Systems. In July 2000 the questionnaires were forwarded to Authorities involved in the assessment of marketing applications and supervision of medicinal products for human and veterinary use in the European Economic Area (EEA) and in EU candidate countries. Also authorities involved in specific areas like inspections related to medicinal products and pharmacovigilance can contribute to and benefit from the comparison and harmonisation of best practices and were invited to participate, as well as the European Commission and the European Directorate for the Quality of Medicines (EDQM), Council of Europe.
The outcome of the questionnaire determined the main areas of interest for EMEA and the Euro-partners to compare systems and processes and agree on the best practices.
Two GRP-QMS benchmarking meetings took place at the European Agency for the Evaluation of Medicinal Products (EMEA) in 2001 and one in 2002. The periods between the meetings were used to implement locally the quality system, to report through the network about the implementation progress and to prepare the programme of the next benchmarking meeting. The choice of a quality system is free and certification is not the first priority. The outcome, the positive impact on the tasks of the competent authorities is of importance. The benchmarking objective is to facilitate harmonisation of the systems, which will allow consistency and best use of resources.
At the meetings the most relevant results, failures and opportunities for improvement were addressed by volunteering authorities followed by a general discussion and exchange of experience on the same topic with the project objectives in mind:
- Benchmarking of quality systems implemented or in development by European and EU National Agencies, who volunteer to share experience in order to harmonise best practices
- Results of the benchmarking should be made available for inter-agency training
- The resulting quality management system should be presented at public workshops to benefit from suggestions for improvement
- Include wherever appropriate comparison with third countries, such as USA, Japan and Canada.
Delegates from 27 European countries, from the Directorate-General for Health and Consumer Protection (European Commission) and the European Department for the Quality of Medicines (EDQM, Council of Europe) shared with EMEA management and staff experience on:
- Practical implementation of a Quality Management System, with particular focus on both motivation of staff and motivation/commitment of management,
- Identification of processes needed for Good Regulatory Practices and documentation of processes in Standard Operating Procedures,
- Establishment of a quality policy / mission statement,
- Communication about the Quality Management System and Good Regulatory Practices within the organisation,
- Activities related to performance indicators and business measurement.
Selected best practices (cost-effective, efficient, and feasible) were furthered with mutual assistance through networking.
Practical implementation of QMS
It was very encouraging to see that great progress was made by several countries since the first benchmarking meeting in March 2001. The main points identified for the success of a Quality System are the motivation of the staff and the commitment of the management. The assistance of consultants, whether used to work for authorities or not and the benefits compared to the costs are useful elements for authorities starting the implementation of QMS. Different from a similar implementation of QMS in industry is the fact that also governmental commitment is or need to be sought in the case of national authorities. The more complex a national regulatory system is involving diverse bodies and different locations, the greater the need for governmental commitment and wish to see a top level decision regarding the Quality System to be implemented. The role of Quality Manager(s) is important. Major success factors are the decision to use internal staff mainly so that staff owns the process, as well as leadership from the top management.
The advantages of a process approach
To ensure consistency, the identification of processes needed for Good Regulatory Practices and documentation of these processes in Standard Operating Procedures (SOPs) are required. The type and level of detail of SOPs is subject of discussion. Sufficiently detailed to provide a clear message to all stakeholders (SOP for internal use and applicant) and remaining practical and therefore used is not an easy task. The availability of clear procedures to applicants for a marketing authorisation is part of the transparency policy. As indicated in ISO 9001:2000 the extent of the Quality Management System documentation can differ from one organisation to another due to a) the size of the organisation and type of activities, b) the complexity of processes and their interactions, and c) the competence of personnel. Moreover the documentation can be in any form or type of medium, which allows authorities in the same way as other organisations to select an electronic format if appropriate. It is essential to pay attention to the processes and start with flow-charts. SOPs should be written and revised in a meaningful way, and should serve users and not the other way around. Processes must be mapped also to identify situations where time can be saved and risks identified. The development of SOPs results in the development of smarter, more efficient approaches to the process by staff involved in the process.
The process approach facilitates the introduction of integrated management. The need to work in a transfunctional way provides opportunities for staff other than just promotion within the hierarchy by increasing experience and enlarging roles, identification with project success(es). A system based on processes is more flexible and facilitates horizontal staff mobility within the organisation. The process approach also facilitates the implementation of an Electronic Data Management System (EDMS), which provides full document control linked with the in-built processes in the system. The key processes must be identified before IT systems are developed. For instance pharmacovigilance experts of EU candidate countries are involved in the EudraNet development process allowing contribution in that area. A fully integrated system allows effective management of procedural, financial and administrative data within an organisation. The EMEA conducts now concerted financial and system audits against contracts and agreements, including those related to IT initiatives, in order to ensure that the agreements are respected. Auditing is a good exercise in getting to know people and using the experience gained with auditing serves the development of own processes in own unit/sector. This is 'working smart' by reducing duplication of work.
Communication about QMS / GRP and integrated management
Communication is necessary to inform, instruct, persuade, motivate, guide and ultimately to optimise behaviour. Benefits of having nominated an internal communication officer include the channelling of information (including avoiding 'E-mail overload') and having a consolidated point and means of communication. The ultimate goal is to improve efficiency of communication, promote best practice and thus save time. The recently created function of EMEA internal communication officer reports directly to the top management. First objective is to differentiate information management and dialogue i.e. 180° (getting the message across) vs. 360° (obtaining feedback). Communication channels are electronic, verbal and visual. Further benchmarking about ways to improve communication and networking between similar functions at the different organisations could be beneficial for management and staff. Communication between the benchmarking partners is equally important.
Performance measurement
In Europe there are important challenges ahead such as IT/European IT systems, orientational planning for the revision of the regulatory system, view to EU enlargement. Listing of main objectives, priorities and performance indicators is crucial for strategic business planning. New reporting elements have been introduced relating to human resources, audits and budget. Performance indicators do not only address the authorisation procedure but also post-authorisation issues i.e. pharmacovigilance and variations. Additionally at the EMEA also scientific aspects are evaluated e.g. by looking into the impact of scientific advice on list of questions/ ultimate outcomes of applications for marketing authorisation.
Performance indicators include moreover external and internal surveys, statistical reporting on scientific output and "unit cost" measuring staff hours vs. predefined activities using electronic time sheets. Staff motivation surveys provide opportunities to discuss results at all levels.
The key aspect of measuring performance is evaluation of trends. The process maps are at the basis of performance evaluation. By introducing the Electronic Common Technical Documents (eCTD) the e-review is induced. IT, networking and electronic review provide experience with possible direct impact on the process of performance indicators' identification, their archiving and inter-agency communication and training. The over-the-web exposure of the regulatory work process, being a subject to online feedback, provides simple but direct-to-evaluate checkpoints for performance measurement. The periodic analysis of incoming traffic /amount in Mbytes per week, month etc./ as well as the trends in amount and profile of the unique visitors can be valuable indicators.
In line with ISO requirements management needs to measure and review performance of operations regularly Based on this review system improvements can be planned and implemented. In order to make this process effective, the approach to measuring performance needs to be directed, indicators defined and applied systematically to all areas of activities. Industry perceptions for a complete process may be different from internal performance measurement criteria. Some aspects may cause delays that are outside the control of the agency, but still affect the perception and, thus, satisfaction of customers. Performance measurements by pharmaceutical industry associations are valuable elements for continual improvement.
The type of performance (e.g. related to public health, customers or mutual communication) and the indicators to be measured can be varied. The statistics can be made available, but assessment of the outcome is more difficult. The perception of different interested parties, mainly industry and patients, can be very different. The main performance indicators should be standardised and shared between the different agencies as far as possible. The way to measure performance becomes a question when resources are limited.
There may be dissatisfaction due to change in legislation and procedures. The satisfaction of the authorities should also be addressed. A combination of objective figures with supplementary and subjective statements from stakeholders could provide a better performance indicator. It is difficult to establish relevant Performance Indicators addressing events beyond the initial tasks. The discussion on defining effective performance measurement tools continues. There is a need to look into risk assessment as well, but authorities are not the owners of factors determining risks subsequent to the initial operations. Could an issue, appearing later for a medicinal product, have been prevented with the tools available at the time of the assessment of an application?
The way forward
Openness is one of the principles of good governance. Networking and benchmarking between authorities will increase, while internally the organisations continue to implement an integrated management system that will be able to ensure the quality of present and future tasks.