GAPP Joint Action

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facilitatinG the Authorisation of Preparation Process for blood and tissues and cells

Abbreviation	GAPP Joint Action
Formation	2018
Type	EU funded project of CHAFEA Health Programme
Legal status	Ongoing
Purpose	Aims at increasing the support offered to the development of a common approach in the Member States for properly implementing Union legislation concerning authorization of preparation processes for blood and tissues and cells.
Coordinator	National Institute of Health (ISS), Italy
Budget	€ 1199824,37
Website	www.gapp-ja.eu

GAPP Joint Action (facilitatinG the Authorisation of Preparation Process for blood and tissues and cells) is a 36 months EU funded project of CHAFEA. Health Programme (ID 78529).Broad geographical coverage is a strong feature of this program with a consortium of 27 Associated and 13 Collaborative partners who represent the Competent Authorities of the involved fields from 16 European countries. The EDQM-CoE, ECDC and professional societies (ESHRE, SOHO) will contribute with international expertise.

Mission

GAPP Joint Action (facilitatinG the Authorisation of Preparation Process for blood and tissues and cells) aims at facilitating the development of a common and optimal approach to assess and authorise preparation processes in blood and tissues establishments (BEs and TEs). Particular attention will be devoted to innovative processes that might come up taking advantage of the work developed in previous EU funded projects/actions.

This Joint Action will clearly contribute to the implementation of Union legislation in the fields of human tissues and cells, blood, providing tools and training to increase harmonisation of those MS activities that regulate the areas of blood transfusion, transplantation of tissues and cells and assisted reproduction, in strong abidance with art 4.5 of Annex I of Regulation 282/2014. These are fields of healthcare that involve a considerable amount of movement of donated substances of human origin between MS and also movement of citizens between MS for treatment, particularly in the field of assisted reproduction.

The aim of the action is to prepare a “Good Practice Guidelines to authorisation and preparation process in blood, tissues and cells” and its three technical annexes respectively on i) authorisation changes in donation, procurement and collection, processing, preservation, storage and distribution (divided in three part blood, tissues and cells, and reproductive tissues and cells); ii) assessing the quality and safety of donor testing, microbial inactivation and sterilisation steps as part of PPA; iii) assessing clinical data as part of PPA.

In addition to this it will be built a model and a tool to facilitate sharing of information among European Union Competent Authorities and a number of CA inspectors will be trained specifically to assess and authorise preparation processes of tissues, cells, reproductive cells and blood products.

Background

There is growing importance in the utility of substances of human origin for a wide range of medical conditions in which blood transfusion, tissue and cell transplantation, including assisted reproduction,offer therapeutic solutions and/or improve the quality of human life.These therapeutic modalities are important areas of healthcare across the EU, and involve a considerable amount of movement of donated Substances of Human Origin and also citizens for treatment between EU Member States, due to unequal access, particularly in the field of assisted reproduction.

Although the aforementioned therapies differ from each other in many technical aspects, they have certain shared ethical, quality and safety requirements that relate to their origin in the human body and their ultimate clinical application in humans. Donation of substances of human origin is based on a common set of ethical principles and good governance mechanisms that guarantee the protection of the fundamental human rights of both donors and recipients all over European Member States. All the areas are overseen, together with organ transplantation, by one group within the European Commission, the group working on Substance of Human Origin (SOHO) and the EU Directives that regulate them have many common elements.

Until now, great progress has been achieved in the EU for ensuring a common level of quality and safety standards (e.g., the need for preventing disease transmission) but therapies based on substances of human origin are becoming ever more numerous and varied thanks to progress in cellular and molecular biotechnology and microbialin activation methodologies, among many others. The benefits of improved and innovative technologies in these fields should be made available for patients via robust authorization procedures where safety and quality are well demonstrated in both low resource and high resource countries.

GAPP Joint Action aims at increasing the support offered to the development of a common approach in the Member States for properly implementing Union legislation concerning authorization of preparation processes for blood and tissues and cells.

The basis for the contents of this Joint Action have not been thoroughly addressed in a substantial way in previous EU funded actions although the possible need for clinical follow-up data as part of Preparation Process Authorization for blood, tissues and cells is being addressed in a work-package of the joint action VISTART (Vigilance and Inspection for the safety of transfusion assisted reproduction and transplantation).

Also two ongoing Public Health Programme projects focused on tissues and cells (Euro-GTPII - Good Practices for demonstrating safety and quality through recipient follow-up and ECCTR- European Cornea and Cell Transplantation Registry) are developing methodologies for such follow up for particular types of tissues and cells. In particular, any possible advantage will be taken from the surveys already conducted while any effort will be taken in order to avoid overlapping of GAPP-JA with these previous projects, through direct involvement of their coordinators.

From a methodological point of view, GAPP will develop an overall guidance on organization of Process Preparation Assessment system at Competent Authorities level (Work Package 5), that will be supplemented by three Technical Annex (Work Packages 6-7-8). As finally durable output of the whole action, a knowledge sharing platform on Process Preparation Assessment will be developed and fed under Work Package 9, whereas training courses addressed to Competent Authorities inspectors will be designed and implemented under Work Package 10.Four horizontal Work Packages 1-4 (Coordination of the action, Dissemination & Communication, Evaluation, Integration in National policies & Sustainability) will support this JA throughout its duration.

The GAPP JA activities will contribute to greater assurance of delivering safe and effective treatments in these fields, regardless of the Member State in which the treatment takes place, where initially highly specific technical knowledge and clinical expertise is requested for assessing and authorizing innovative processes.The contribution of GAPP is considered pivotal, in order to ensure that all substances and procedures are subject to European safety and quality requirements.

All Member States will appreciate the benefit of a clear, agreed-upon, harmonized approach to the Process Preparation Assessment with reciprocal advantages in enhancing their technical and organizational skills by comparing the best practices in the fields of blood, tissues and cells. Some Member States will have the opportunity to learn from other Member States where regulatory systems have been already consolidated in this particular field.The sharing of expertise and development of clear guidance will result in the provision of safer and better quality blood, tissue and cell healthcare services to patients in the EU, thanks also to a better attention for impact on patients undergoing treatment with novel therapeutical approaches. In this regard all patient transfusion, tissue or cell transplantation or assisted reproduction treatment will be targeted for quality improvement by this action.

The common European level framework which is to be achieved by addressing the activity of Authorizations of Preparation Processes by Competent Authorities contributes in reducing health inequalities by increasing safety and even encouraging innovation. The general impact will be beneficial for EU citizens and aid in better guaranteeing access to harmonized health care throughout the Union, especially in a field increasingly open to  technical and scientific advances.

EHA supports the project as a Collaborating Stakeholder, contributing expertise and contacts as well as assistance on communication and dissemination.

Work packages

WP1 - Coordination of the action by lead ISS-CNT-CNS

Start month:1 - End month: 36

Objectives

This WP is aimed to manage and coordinate the project and make sure that it is implemented as planned, managed following the EC rules and procedures.

The coordination role, assumed by the project leader, is intended to:

• coordinate the action transversally and vertically:
  • supervise the design and implementation of the single work packages, supporing WP leaders,
  • supervise vertically the work carried out in each WP ensuring the expected deadlines and deliverables are met;
  • ensure a steady information on WP progress;
  • monitor transversally the compliance of each partner and assess whether the activities are balanced or not, and in this case allowing to jeopardize the performance of the partners in the other WPs.
  • guarantee quality working procedures, oriented to results and aims, transparent and balanced within the transnational consortium;
  • design a General Working Plan for the JA and coordinate specific working plans within each WP;
  • ensure a permanent and transparent communication within the consortium, and dynamise JA implementation
  • motivating all partner organisations for guaranteeing a balanced participation, avoiding any inactivity during specific periods of the JA life.

Description

Task 1.1- Organization of general plenary coordination meetings, where Steering Committee will convene: Kick-off (M2), intermediate meetings (M18) and final meeting (M36); interim WP meetings for reaching agreements on specific issues, developing work, and exchanging relevant information, including working progress will be held by conference calls. The final meeting will take place together with the final dissemination conference.

Task 1.2 Project working bodies (Project Committee will be constituted by all partners involved in the Consortium; WPs Steering Committee will be composed of the members of the coordination unit and the leaders of the WPs, being this Steering Committee an operational body for collective decision-making and reporting on the execution of the project).

Task 1.3 A Manual for the financial and administrative management of the JA will be prepared and circulated among partner, where the different reporting periods will be defined, along with management and financial rules and procedures (M4).

The General Management team will include two scientific managers, CNT and CNS General Directors, that will have overall responsibility for the whole joint action, two project management experts, a senior biologist team leader and a senior haematologist leader plus two technical coworkers. Project managers will supervise all the actions and works performed and steer the coordination team/unit.

The whole team, constituted by CNT-CNS staff, will monitor the progress of the Joint Action transversally and vertically, will establish communication with the steering committee on a regular basis, will report to the Directors of the Joint Action.

WP2 - Dissemination & Communication by lead PGH

Start month:1 - End month: 36

Objectives

The overall objective is to identify and reach the target audience and stakeholders, including EU and national policy makers, academic institutes, professional associations, end users and the public, in order to raise their awareness regarding the findings of the consortium and to encourage them to support and adopt the commendations on the “Authorisation of preparation processes in blood and tissues and cells”. More specifically, the objectives of WP2 are:

• To define and establish the consortium’s dissemination and communication strategy.
• To define and reach the target audience and stakeholders at the level of institutions, professional societies, policy makers and final users.
• To raise awareness of the target audience, stakeholders and community in general, as regards the project activities.
• To provide the means for dissemination and communication of the JA actions and outputs

Description

This WP will be co-lead by the Papageorgiou General Hospital and the 7th Health Region of Crete

WP2 is dedicated to the dissemination of the action and its deliverables. Dissemination refers to the process of making the results and deliverables of the action available to the stakeholders and a wider audience.

Here all actions planned to ensure that the results and deliverables will be made available to the stakeholders and can be used by them will be described. WP2 activities will include the development of the dissemination plan, a stakeholder analysis, identification of target groups, adequacy of channels used to reach them, and actions to ensure proper visibility of European Union co-funding.

The dissemination strategy should pay attention to the transfer of knowledge and to the processes needed for embedding and future take-up. The sustainability of the dissemination actions will be properly addressed.

The Dissemination WP team will include two Project Managers (one from Papageorgiou General Hospital and one from the 7th Health Region Greece) who will have the overall responsibility of the WP, one project mananger expert who will support and monitor all dissemination activities, two haematologists experienced in preparation processes on blood, tissues and cells, two highly qualified administrators, two administration staff, three information technology experts and one web graphic designer. The whole team consists of the staff of the Papageorgiou General Hospital and the 7th Health Region / University Hospital of Heraklion and two subcontractors (one dissemination/communication expert and the graphic designer). An experienced conference organizer will be also subcontracted for the final conference organization

Task 2.1 – Dissemination and Communication Strategy (M1-M36)

The task will define a detailed dissemination strategy to ensure high visibility and impact for the project. In specific, a dissemination plan covering all the duration of the project will be authored describing the aims and objectives of the JA, the actions to be disseminated, the target audiences/groups and stakeholders, the benefits to end users, the dissemination methods/activities, the timescales and responsibilities of the members of the team, the targets, the estimated costs, the evaluation and criteria for success. This task will also include planning for scientific publications in highly-ranked, open access journals, presenting the project concept, vision and results. Interaction and synergies with relevant initiatives/bodies/organizations will also be defined. Emphasis will be given on establishing measures as regards the sustainability of project outcomes. The dissemination strategy will be revised periodically based on the feedback and the achieved results to ensure that the targeted events maximize visibility and that the dissemination activities reach the targeted audience.

In this frame, a dissemination meeting will be held before the revision of the Dissemination Plan, in order to ensure that all partners are “in the same page” regarding the necessary dissemination and communication activities.

Task 2.2 – Dissemination and Communication Package (M1-M36)

A multi-strand approach will be used to ensure the effectiveness of the dissemination actions of the Consortium. This includes:

2.2.1 Configuration of the project Identity: Design the project logo, production of a design for printed material, production of banners, posters, flyers, preparation of the newsletters, production of video material, as well as official project templates for PowerPoint presentation. The Layman Brochure will be as well developed at month 3. The Brochure will address to all target groups including general public and it will contain a short description of the project, the aims of the work packages as well as the list of all the associated and collaborating partner organizations involved in the Action.

WP3 - Evaluation by lead MOH - HR

Start month:1 - End month: 36

Objectives

This WP aims to ensure that the project is being implemented as planned, reaches its objectives and produces high quality deliverables, especially monitoring activities within the WP5-WP10, e.g. for all meetings and training events under such WPs, questionnaires will be distributed to ascertain how participants evaluated the usefulness and organisation of the event. To achieve the aim, beside other activities WP leader will attend relevant project events according to the evaluation plan. In addition, an evaluation of whether project outputs fit the purpose will be carried out. The evaluation WP will also take advantage of the contribution of an External Advisory Board to be set up at the beginning of the Action. The Board will be involved in plenary meetings and will deliver inputs for both deliverables and evaluation reports for this WP. The composition of the EAB will take into account the different fields covered by this JA in terms of expertise and therefore is going to be made of 6 experts; one expert for each SoHO field (blood, tissues and ART), one expert for TTD testing, one expert for microbiology (sterilisation and pathogen inactivation issues) and one expert in clinical trials).

Description

The progressive achievements of Action activities and quality of deliverables will be continuously monitored and reported to the PPM. All associated partners and project events participants will contribute to the work of the WP3 by providing their own evaluation of all events attended. EAB will give expertise within their competences in evaluation of specific scientific/expert issues addressed in events and outputs of the Action where such an expertise is applicable.

The work will be carried out in two aspects: internal and external evaluation.

Within all relevant project’s events (including outputs) following elements will be evaluated:

• organisational elements (venue, traveling organisation, accommodation and related information…),
• technical elements (core materials and information flow, course, content and goal of the event, etc) and
• professional/scientific elements (deliverables).

The WP leader will produce an interim and final report, with executive summary shared with internal and external stakeholders. The final evaluation report will be focused on the outcomes and the reached objectives but also on the impact of the Action having in focus particularly sustainability of outcomes. Evaluation reports will be a standing item on Steering Committee meeting agendas, ensuring that quality of outputs in both means accuracy and contemporaneity is always a top priority.

At the beginning of the project, in cooperation with EAB where applicable, will be defined sets of indicators according to SMART criteria (paying in particular attention to have quantifiable indicators wherever possible) to assess performance. Set of indicators will be established for each specific objective of the project and will comprise:

• Output indicators linked to results
• Impact indicators linked to objectives

For single deliverable quality and applicability will be assessed based on, for example, following quality indicators:

• timelines of outputs
• comprehensiveness of collected data
• critical/analytical nature of conclusions
• clarity of conclusions/proposals
• realistic nature of conclusions/proposals
• adequacy of MS representation
• clarity of information presented and recorded.

Surveys will be conducted through questionnaires structured as following:

• enabling analysis and grading
• reasonably short (up to 10 questions)
• simple language
• minimal likelihood of misunderstanding
• close ended format (fixed answer set)
• dichotomous questions (yes/no) preferred
• requests for narrative answers avoided
• even number rating scale (to avoid „golden middle” answers)
• opportunity for expressing opinion (one open ended question)

Through the whole duration of the project WP leader and EAB will tightly cooperate aiming to produce timely and harmonized WP3 outputs. To achieve that leader and EAB will have 2 technical meetings which can be organized as video/teleconference if considered appropriate or back-to back to other project event (such as technical or plenary meeting for example).

Task 3.1. Definition of a project evaluation plan

In the first 6 months of JA lifetime project evaluation plan will be defined.

Task 3.2 Internal evaluation

Through the task all relevant project’s events and outputs, such as technical meetings, plenary meetings, workshops/trainings, deliverables etc. will be assessed and evaluated.

The work methodology will include:

1. Data recording out of routine documentation of horizontal WPs and pre-release deliverables (training materials, guidelines, operations manual, recommendations, results of pilot projects, etc.),
2. Surveys,
3. Observation (support, early reaction, data security) with a calendar of milestones.

Task 3.3. External evaluation

Through the task all professional/scientific elements of each project’s event and output, such as technical meetings, plenary meetings, workshops/training, deliverables etc will be assessed and evaluated under guidance and with inputs of EAB, to be composed of 6 internation.

WP4 - Integration in national policies and sustainability by lead IVO

Start month:24 - End month: 36

Objectives

This WP will set up a plan to describe the potential of GAPP results for integration in policies (at national, regional or local levels) and to ensure the sustainability of the JA activities at national or on the local or regional level. As a final result a common proposal for supporting a sustainable implementation in single countries will be agreed upon. Through the development of plans and tools for implementation in the MS of the outcome from this JA.

The work will focus on implementation and thereby sustainability at two levels.

• At the CA level for regional/ national policies and eventually homogenous within Europe
• At the professional level for acceptance and thereby integration into good practice at national/ European level.

Description

WP4 will set up a model for CA´s in the MS to incorporate the results of the JA into policies at national/local level. Along with such policies WP4 will provide additional input to the work of WP2 (dissemination) and evaluate the acceptance (at the CA and the professional level) of the results in this JA. Toward the end of the action (M30) the analysis of possible barriers and obstacles to integration and sustainability of JA results in single countries will be performed as part of the general survey on integration in national policies and recommendations for overcoming these will be added as parte of final sustainability report. Consensus about the criteria in the process for authorisation when introducing new methods in Blood, Tissues and Cells including ART, will eventually create recommendations of good practice among the professionals and acceptance of future regulations. The issues and plans for development and subsequent sustainability of the knowledge-sharing platform whose concept model will be defined under WP9 will be as well analysed and clarified.

At the CA level:

In particular the deliverables from WP5 will provide the basis for recommendations, depending on the various institutional organisations in the different MS.

Also the deliverables from WP5 with guidance on what to authorize, how to apply for authorization, definition of significant changes of processes as well as suitable teams for authorization will be important parts to integrate at the level of CA in the different MS.

Likewise the guidance on assessment of validations from the work of WP6 and the impact of clinical data from WP8, will have to be implemented at the CA level and included in the customized tool-box for the different MS.

Most likely it will be necessary to define a minimal requirement at the CA level and maybe rate the suggested recommendations from basic/acceptable to a desired level. We have to take into account that some MS already have working processes for authorization and licencing of new methods (at least in some areas in this sector) whereas others do not. Thus, the plan for implementation will be created as a ladder where the CA can introduce the recommendations/ requirements stepwise which will facilitate adjustments also at the CA level.

At the professional level:

An important part in implementation and sustainability of requirements and recommendations is to obtain consensus at the professional level. The results of the JA should be accepted by the professionals, preferably through international organisations (EBA, ESHRE, EATB, EEBA JAICE etc). These organisations are included as collaborating partners in WP6. WP8, with focus on clinical data as part of the authorization will have the output from other projects as a basis (VISTART, EuroGTP and ECCTR) where professional organisations have participated. WP4 suggest that the deliverables from WP6 and WP8 should be presented at the European meetings held by these associations, also described in the dissemination plan by WP2.

In this WP, the National Tissue Council (within the Swedish Association of Local Authorities and Regions) will be collaborating partners. The Tissue Council have working groups for Blood, ART, HPC and one for each regenerative tissue and one of their tasks is to provide guidance to tissue establishments. Thus, their role as collaborative partners will be to provide expertise and evaluate the recommendations and added value of the results from the JA and provide recommendations to the tissue establishments at the national level.

Work plan

Task 4.1 A pilot for integration of PPA in national policies in SE

In Sweden, it is the National Board of Health and Welfare (Socialstyrelsen) that is the regulatory CA transposing the Swedish laws on Blood safety and Quality and safety for tissues and cells respectively into regulatory acts. Thus, these acts regulate what should be done whereas IVO has the mandate to write regulatory acts on how it should be.

WP5 - Development of Overall Guidance on organization of PPA system by lead HPRA

Start month:2 - End month: 32

Objectives

This WP shall review the existing guidance relevant to PPA procedures including those that were, developed by previous projects (EUSTITE, VISTART, EUROTGPII and ECCTR); survey and evaluation of the existing PPA systems in force in the various Member States and, based on this, develop a set of best practice guidelines for PPA systems.

Description

This WP will develop guidance on how a Preparation Process Authorisation programme should or could be organised. This WP will take advantage of the results of the VISTART Joint Action as far as analysis of existing procedures and drafting of authorisation principles for novel processes is concerned, as well as the outcomes of the EUSTITE, EUROGTPII and ECCTR projects, that should however be extended to the blood sector. In order to ensure comprehensive consideration and review of VISTART WP5B, EUROGTP II and ECCTR outputs and to ensure that development of the relevant technical annexes and guidelines, leaders of these projects/actions/WP will be involved in two devoted meetings. Revision of guidance for blood establishments will be as well ensured by adhoc subgroup.

Lessons learned from experience in the systems for authorisation of medicinal products and medical devices at national and EU level will be examined and compared with existing experience in the TCB fields.

The following activities will be included:

• Development, circulation and analysis of results of a questionnaire survey of MS to explore and have a comprehensive picture of existing PPA systems – supplementing the VISTART WP5 Part B survey.
• Desk-based review of product authorisation systems in place in other relevant sectors (e.g. medicines, medical devices)
• Organization of a multi-country workshop to further explore organizational and procedural models identified by the survey and to identify strengths, weaknesses and best practices.
• Development of general good practice guidelines for PPA – putting a system and Standard Operating Procedures in place at the Member State level, including a methodology to inform blood and tissue establishments (BE/TE) regarding those procedures.

The guidelines shall include:

• An overview of the single authorisation steps from the request submitted by a BE/TE to the release of authorisation by CA
• Timing of application for PPA
• Definition of significant change in preparation process
• Terms for application (also building on the outcomes of VISTART WP6 - manual for inspections)
• Organisational models and mandates of the CAs responsible for the PPA
• Optimal composition of the assessing team in the CA (members' qualifications, background, use of external experts etc.), definition of inspectors’ involvement,
• Definition of types of authorisation (e.g. full, conditional, temporary – taking into account the outcomes of VISTART WP5 part B)
• Recommendations on how to analyse and address ethical issues.
• Development of model template forms for PPA.

Task 5.1 Review and revision of the outcomes of EUSTITE, VISTART WP5B, EUROGTPII and ECCTR projects results

Revision of the results of VISTART WP5B, EUROGTP II and ECCTR projects related to the authorisation of preparation processes for tissues and cells, so as to be applicable to blood establishments.

Task 5.2 Survey

Design a survey to review the implementation of the outputs from the previous projects and to have a comprehensive overview of the PPA systems in place in each of the Member States.

Task 5.3 Desk-based review of existing PPA systems in place in other relevant sectors

Task 5.4 Multi-country workshop

This workshop will have the objective of further exploring the different organisational models for PPA used by the various Member States and also to identify the associated common best practices.

Task 5.5 Development of Good Practice Guidelines for PPA

Elaborate good practice guidelines for PPA based on the requirements defined by the European Directives, analysis of the outputs of previous projects and the review and analysis conducted as part of this work package, in order to define a common approach and methodology.

WP6 - Technical Annex 1 to overall guidance: Suthorisation of changes in donation, procurement and collection, processing, preservation, storage and distribution* (including labelling and package inserts) by lead NBC

Start month:1 - End month: 30

Objectives

The quality of the preparation of blood, tissues and cells that will be used in a patient has an impact on patients and will condition on the authorization of preparation process steps. Clear quality criteria for different blood components

and tissues and cells types need to be established.

So the WP will be divided in two parts:

The first part will involve the definition of key quality and safety criteria for each category of blood component, tissue or cell. The resulting deliverables will highlight the criteria that need to be validated or verified through in vitro or by clinical studies, and will build on existing work carried out by the Council of Europe (EDQM).

The second part of this WP will develop guidance on how to ensure these criteria are met through in vitro validation, in-process verification or clinical studies.

Description

This WP will be led by the National Blood Centre of Lithuania (NBC)

The WP leader will be supported by experts from two other partners from Lithuania, the LUHS Kaunas Clinic and the Santaros Clinic. This team will monitor the progress of the WP6 transversally and vertically, establishing communication with other partners and the co-ordinators of the Joint Action.

Regarding the general organization of the WP this work package will deal with two issues:

Part 1: Definition of the critical characteristics/properties (criteria) for each category of blood component, tissue or cell type (referring to EU blood legislation 2004/33/EC, EDQM blood component monographs and Tissue & Cell guidance). Examples of characteristics/properties might be the vitality of cells following processing, biomechanical strength parameters, a minimum volume, tissue integrity, a minimum number of motile spermatozoa. Where such criteria have already been defined by others, particularly for blood components, the group will review and build on established standards.

Part 2: Guidance on the assessment of methods to demonstrate achievement/maintenance of the critical characteristics/properties for each category of SoHO, in particular where changes are proposed/implemented in one of the preparation steps. The guidance will take into account the degree of risk to the patient from the blood component or tissue and cell product based on parameters such as historical data, degree of change in processing or testing. Evidence will include published and laboratory studies conducted by the applying BE/TE criteria identified under Part One and used to determine the depth of validation needed e.g. when the new process has been validated elsewhere, compared to cases where the new process has not been validated before. For reproductive T&C, the validation will take into account long term results regarding the health of the newborn baby. The methods proposed for the demonstration of compliance with the criteria could include in vitro validation studies or in-process verification steps.

The work of Part I will be developed by the organization of three (3) technical meetings for each sub-group. Meetings are going to be held at the same time and place and working groups will work in parallel sessions. During the technical meetings (M 3, M 8, M 13) the working group will determine and further elaborate the scope of characteristics/properties criteria, evaluate existing criteria and methodology, review the existing variety of examples, published studies, etc.

The work of Part II will be developed by the organization of three (3) technical meetings for each sub-group (M18, M.22, M.25). During the technical meetings the working group will study of the depth validation needed, identifying the cases when validation is applicable to the new process; evaluate the draft guidance of the characteristics/properties criteria for each category of blood component, tissues and cells, especially considering proposed changes implementation.

At M27 the closing technical meeting with participants of Part 1 and 2 will take place to agree on the last amendments needed in the definitive version of the guidance documents.

Finally as associated partner in this WP and to achieve at best WP9 objectives, PEI will work in parallel in this WP in order to build a data model of information on preparation processes (authorisation of changes in donation, procurement and collection, processing, preservation, storage and distribution (including labelling and package inserts).

WP7: Technical Annex 2 to overall guidance: assessing the quality and safety of donor testing, microbial inactivation and sterilisation steps as part of PPA

Start month:2 - End month: 26

Objectives

This WP focuses on those technical aspects of processing that aim to reduce the risk of infectious disease transmission, in particular donor testing, microbial inactivation during processing and sterilization of final products.

The WP will lead to a technical annex that will include an assessment for three kinds of biological products: blood (and blood-derived products), tissue and cells for replacement, haematopoietic stem cells and reproductive tissues and cells. The biological quality and safety parameters will be defined for each step from donation to the application on recipients, which are mainly:

- Donor testing

- Microbial inactivation/sterilisation during product processing

- Evaluation of the microbial status of final products

The safety will be assessed for microbiological pathogens like fungi, viruses and other kind of agents (e.g. prions)

Description

this WP will be co-lead by ABM, France and FIMEA, Finland

The work will be developed by teleconferences, emails and during four technical meetings.

During the 1st technical meeting (M2) the working group will be split in subgroups in relation to different tasks (see below) and will define the general methodological approach.

During the further three technical meetings (M8, M14, M20), the working group will focus on the following topics/chapters of the technical annex:

Assessing and authorising methods related to donor testing, microbial inactivation, microbial status of final products;

Requirements for selection, validation and performance of donor infectious marker testing kits and other methods;

Requirements and criteria for laboratories performing donor testing;

Criteria for validation of microbial inactivation steps;

Criteria for validation of sterilisation processes.

Concerning the division of tasks between involved WP leaders and partners:

• ABM will be in charge of the ART field.
• FIMEA will be in charge of the blood field.
• For the Tissue & Cells field: ABM will be in charge of the HSC part, FIMEA of the other Tissues & Cells part.

At M25-26, the 4th final technical meeting will take place in order to agree on the last amendments needed in the definitive version of the deliverable.

Finally as associated partner in this WP and to achieve at best WP9 objectives, PEI will work in parallel in this WP in order to build a data model of information on testing procedures (assessing the quality and safety of donor testing, microbial inactivation and sterilisation steps as part of PPA).

WP8 - Technical Annex 3 to overall guidance: assessing clinical data as part of PPA authorisation by lead FIMEA

Start month:1 - End month: 30

This WP will be co-lead by Laakealan Turvallisuus-JA Kehittamiskeskuss (FIMEA), Finland - Banc de sang i teixits (BST), Spain

Objectives

WP 8 aims at:

• Defining the current state of the art of existing collected clinical data, namely in order to define a catalogue of clinical data, appropriate to provide information on the quality and safety of human blood, cell, and tissue therapeutics once applied to patients, under the conditions of current state-of-the-art processing and testing protocols for human blood, cell, and tissue therapeutics
• Defining a risk-based framework to assess whether the current state-of-the-art criteria fit to a new processing or testing protocol. Such criteria should be appropriate to evaluate the established catalogue of clinical data for completeness and suitability in case of introduction of innovation to the current processing and testing protocols for human blood, cell, and tissue therapeutics
• Defining a methodological framework, to evaluate quality and safety based on clinical outcome data requested for authorization processes upon introduction of innovation to the current processing and testing protocols. The framework should have adequate characteristics in order to allow for an appropriate degree of harmonization as well as for an appropriate degree of flexibility, to evaluate quality and safety of human blood, cell, and tissue therapeutics based on clinical outcome data requested for authorization processes upon introduction of innovation to the current processing and testing protocols for human blood, cell, and tissue therapeutics
• Building a data model of information on clinical outcome of application of human blood, cell, and tissue therapeutics, building also bridges to existing clinical databases such as ECCTR, EBMT, EuroGTPs, registries.

Description

Part A)

1. Specification of a set of existing clinical data appropriate to provide information on the quality and safety of human blood, cell, and tissue therapeutics once applied to patients, under the conditions of current state-of-the-art manufacturing and testing protocols (6 months)
2. Specification of appropriate risk-assessment models taking into account cumulative and aggregative risk assessment (1.5 months)
3. Specification of criteria, appropriate to define “innovation” in manufacturing and testing protocols for human blood, cell, and tissue therapeutics taking into account the output of work package 5b of VISTART (1.5 months)
4. Specification of a risk-based set of criteria, appropriate to evaluate the established catalogue of clinical data for completeness and suitability in case of introduction of innovation to the current manufacturing and testing protocols for human blood, cell, and tissue therapeutics (6 months)
5. Review of data set by experts and stakeholders for completeness and relevance (3 months) Part B)
6. Setting up tools for data compilation (2 months)
7. Proof of concept: data acquisition, evaluation of quality and validity of data ( 12 months)
8. Definition of a methodological framework, appropriate to allow for an appropriate degree of harmonization as well as for an appropriate degree of flexibility, to evaluate quality and safety of human blood, cell, and tissue therapeutics based on clinical outcome data requested for authorization processes upon introduction of innovation to the current manufacturing and testing protocols for human blood, cell, and tissue therapeutics (12 months in parallel to 6 / 7)

Teleconferences, e-mails and five technical meeting will be carried out. During the first technical meeting (M2) practical working plan will be discussed and responsibilities agreed. Second, third and fourth technical meetings will be held at M8, M11 and M23 to finalise D8.1, D8.2 and D8.3 and a fourth technical meeting at M31 to finalise D8.4.

As an associated partner in this WP and to achieve at best WP9 objectives, PEI will work in this WP in order to build a data model of information on clinical outcome of application of human blood, cell, and tissue therapeutics, building also bridges to existing clinical databases such as ECCTR, EBMT, EuroGTPs, registries.

WP9 - Knowledge sharing on PPA between EU CAs by lead PEI

Start month:12 - End month: 36

Objectives

This WP aims at laying the grounds for a future implementation of the criteria catalogues resulting from WP 6-8, thus allowing for a standardised, electronically supported assessment of quality, safety and efficacy of blood, cells and tissues,

in the case of state-of-the-art processing procedures as well as in the case of innovative processing procedures.

Description

From a methodological point of view the work will be performed in three blocks:

1. Building on the data models set up in WP 6, 7, 8, these data models will be integrated into a structure that will display the dependencies of 1) preparation methods, preparation steps, in-process controls and related results, 2) testing methods, results and specifications of the final product, 3) clinical outcome data demonstrating efficacy and safety of the product upon application to a patient
2. Building the framework for an electronically supported authorization process based on the integrated data model: Identification and evaluation of checkpoints critical to approval of blood, cells and tissues
3. Development of the concept of a platform to implement A, B. Part A, B and C will be developed in parallel. Part A covers the building on the data models set up in WP 6, 7, 8. The activities will be developed as follows and according to the indicated timeline:

• IT security and data privacy concepts, data access concepts (3 months)
• Organization and Structure of the electronically usable criteria catalogues and of the platform (3 months)
• Architecture design for criteria catalogue and platform based on international standardization efforts and previously derived requirements: architecture model, description of data exchange/integration and security components (e.g. identification and authentication, Authorization, Logging, pseudonymization and anonymisation) (6 months)
• Aggregation of the data structures of the data sets on authorised preparation processes, testing methodologies and clinical outcome criteria to a common domain model and specification of data structures and data semantic using existing standards as a technical representation of the domain model (12 month)

WP10 - Training courses and manual for training by lead KCBTiK

Start month:20 - End month: 36

Objectives

On the basis of agreed documents: “Overall Guidance on organization of PPA system” and technical annexes, this WP will organise training courses and prepare “Manual for training CA inspectors that assess and authorize preparation processes of tissue, cell, and blood products”, to disseminate the approach throughout Member States. Possible overlapping with existing general inspection documents such as the EC Operational Manual for Inspections of TE and the recently issued deliverable by VISTART JA will be taken into account and clarified. In any case GAPP manual and subsequent training will only focus on assessment and authorization of PPA processes.

Training course will be open to all Member States countries, as well as to Serbia and Moldova

Description

The work of WP10 is strictly connected to the final results of the WP5, WP6, WP7, WP8 and WP9,

This WP will be led by the KCBTiK, a budgetary unit submitted to the Polish Ministry of Health, which tasks include the supervision and inspection of tissue and cell banks in Poland as well as the organisation of training courses on the recovery, collection, testing, processing, sterilization, storage and distribution of tissues and cells.

Task 1: design of training course.

Considering how extensive will be deliverables provided by the above-mentioned WPs, in the second part of the project two technical meetings will be convened by the WP leader. During the first technical meeting of WP10 (M20) the working group will agree on the design of the face-to-face training course contents: training materials incl. examples, case studies etc. After the first face-to-face training course, a summary will be provided by tutors with practical details and prepare the issues concerning a manual content will be discussed as well. At M35 the closing technical meeting will take place to agree on the last amendments needed to the definitive version of manual.

Task 2: face-to-face training

The face-to-face training courses will take place at M30 and M33 and each of them will last 2 full days at least, including theoretical and practical training. The arrival of participant shall be planned a day before the beginning of the course and their departure shall be planned the day after the ending of the course. The training courses will be organised in Poland and all the EU CA from both blood and tissue and cells fields will be invited to attend it. Two persons per organisation will participate to the training. Further participants could attend upon budget availability of their institutions or personal coverage of travel expenses.

Task 3: Manual for training CA inspectors

The training course designed and held in this work package will be documented. All materials such as lectures, examples, case studies will be used as the basis for the preparation of the Deliverable 10.1 “Manual for training CA inspectors that assess and authorize preparation processes of tissue, cell, and blood products”. The manual will be made available at M36 to all Blood, Tissue and Cell Competent Authorities in electronic version downloadable from project website and from ECAS, so that they can use them for national or regional inspector training in the future.

Conferences - meetings

• KICK OFF MEETING, 7-8 June 2018, Rome, Venue: Italian National Institute of Health – room BOVET, (Via del Castro Laurenziano 10)
• GAPP TECHNICAL MEETING, A Technical Meeting for WP5, WP6, WP7, WP8., 20-21 September 2018, Paris, Venue: Agence de la biomédecin, 1 Avenue du Stade de France, 93210 Saint-Denis)
• 2nd Expert Workshop, GAPP WP6 – 2nd Expert Workshop, 20th May 2019 – ABM, Paris, France, Venue: Agence de la biomédecine, (1 Avenue du Stade de France, 93210 Saint-Denis)
• The Third Congress of the Romanian Society of Bone Marrow Transplantation, Bucharest on 9-11 of May 2019
• Invitation to a meeting of the Competent Authorities for Tissues and Cells, Brussels - 13-14 May 2019
• GAPP JA at the ΕΗΑ conference from June 13-16/2019, in Amsterdam
  

External links

• Website
• Facebook Page
• Twitter Page
• CHAFEA Project Webpage
• Partners Map

References

This article "GAPP Joint Action" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:GAPP Joint Action. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.

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