FIND Project Management:
Standard Operating Procedure (SOP) - at a glance
1. FIND Quality Management System
The FIND Quality Management Systems (QMS) were audited in June 2007 by the SWISS TS / TÜV-Süd authority who confirmed that all processes at FIND were structured, organized and documented at a highly qualified level. It was remarked that ISO standards were being implemented throughout all organizational processes and procedures. As a result, FIND was certified for “Project Management for Design, Development and Manufacturing of IVDs, Evaluation and Demonstration of IVDs” in compliance with international standards 13485:2003 and 9001:2000. FIND’s Quality Manual is the principal quality procedure document. Its project management strategy is described in a dedicated Standard Operating Procedure manual entitled “Project Management SOP QP 05-00-01” (PM SOP). Compliance of all project-related processes with the PM SOP is a prerequisite for FIND ISO certification. FIND is dedicated to a process of continuous improvement and review of both the Quality Management Systems and the objectives embodied in them. FIND senior management defines annual quality objectives and evaluates performance of the organization according to targets attained. Achievement of planned project milestones within the projected timelines is one of the most important performance indicators of high quality project management and is assessed on a regular basis.
2. FIND projects
By way of its strong commitment to quality systems, FIND aims to provide customers with innovative and affordable in-vitro diagnostic (IVD) products for all levels of the health care system. FIND does not own manufacturing facilities, design or development laboratories, clinical trial sites, reference laboratories or laboratories for quality control, and has no capabilities for storage of biological reference material, or marketing and sales. All functions necessary for design, development, manufacture, evaluation and demonstration of IVDs must be obtained from FIND cooperation partners, since all FIND projects are planned and executed with partners. FIND’s primary role is the management of projects with subcontracted partners.
Back to top
Typical projects
FIND is carrying out more than 35 projects in three major disease areas: Tuberculosis, Human African Trypanosomiasis and Malaria. All projects are structured into phases and milestones. Milestones require the detailed, documented attainment of pre-defined targets. Most projects entail the development and/or validation and distribution of in-vitro diagnostic products to FIND target markets and are called “typical projects”. Typical projects begin with the
Concept phase and are walked through
Feasibility,
Development,
Evaluation,
Demonstration,
Access and
Impact, a total of seven phases and seven milestones.
Table 1: Project phases and milestones of typical projects
Back to top
Non-typical projects
“Non-typical projects”, on the other hand, are not aimed at specific milestone phases such as Feasibility, Development, Evaluation or Demonstration of a diagnostic product for distribution to FIND target markets. Instead, they facilitate IVD performance evaluation or adoption in FIND target markets. Examples of non-typical projects are:
- Development of a central specimen bank
- Implementation of laboratory training programs at potential trial sites
- Projects to facilitate laboratory preparedness and uptake of new diagnostics at selected sites in FIND target markets
- Preparation of business plans or market reports
A project milestone defines the completed achievements of a phase. Achievements must be reviewed and approved by senior management at project management meetings as described in the FIND milestone review process. Planning documents of the next project phase must be prepared and signed off prior to the start of the next project phase activities.
Management of
non-typical FIND projects
Back to top
3. Project Management
Project leaders are responsible for the entire project through each phase process. Project leaders are supported in all their tasks by functional units such as project management, finance, contract management, human resources, and the Chief Scientific and Senior Technology Officers. Project leaders are responsible for finalizing all necessary documents for the project history file (PHF). Documents to be archived in the PHF include: records of conferences or meetings, trip reports, publications, milestone-related document deliverables, agreements, study protocols, agendas and minutes of project management meetings, as well as documents that trace back actions, decisions and results of each project. The PHF is managed and monitored by the Office of Project Management (OPM) and is kept up-to-date by designated staff members.
The following tasks are the responsibility of the project leader who is accountable for the project, all project-related decisions and actions:
- Initiating projects
- Carrying projects successfully to last project milestone
- Proposing partners, cooperating with partners and tracking achievements
- Managing and tracking approved budget, expenses, and timeline
- Guiding all project-related activities, including contracts and clinical trials
- Preparing all milestone-related documents and applying for milestone approval
- Preparing trip reports and meeting minutes
- Providing Document Controller with project-related documents for PHF and ensuring completeness of PHF dossier for his project at any time
- Ordering and shipping (i) kits / reagents / devices for trial sites (ii) reference materials (from collection sites to repository, trial sites and cooperation partners)
The Office of Project Management (OPM) coordinates and prepares monthly project management meetings (PMM) to monitor and navigate all projects by FIND senior management. The OPM organizes shipment of all clinical trial material to trial sites in developing countries in compliance with national and local regulations. Members of the OPM are:
Senior Medical Officer, Head of OPM and Regulatory Affairs
Project Manager, Officer of Regulatory Affairs
Project Manager, Officer of FIND PHF
Logistics Officer
Back to top
4. Quality assessment of cooperation partners
FIND, together with its cooperation partners, is committed to meeting the needs of its customers in low-income economies by designing, developing, manufacturing, as well as evaluating the performance and demonstrating the efficiency of IVDs for infectious diseases in a manner which ensures accessibility at all levels of the health care system. Partners are selected by FIND senior management and are subcontracted and commissioned to take over specific activities throughout all or partial phases of the project. Industrial partners are responsible for development, manufacturing, registration, marketing, distribution, customer support, and market vigilance of IVDs. According to policy, FIND subcontracts manufacturers that comply with ISO and IVD-GMP standards in design, development and manufacturing of innovative new diagnostics. This will ensure meeting targets of robust and reproducible field performance according to set product specifications for FIND target markets, health care level and intended use of new diagnostics. FIND complies with all national regulations governing its target markets. Sites for development and evaluation trials will be certified according to FIND trial site standards whereas demonstration trial sites may be exempted from certification, and must fulfill real field conditions. FIND cooperation partners have to undergo due diligence assessments of technical, financial and/or regulatory status to prove compliance with quality standards and regulatory demands on design and development, manufacturing, marketing and distribution of IVDs. The following assessments are scheduled:
- Technical due diligence inspection
- Financial due diligence inspection
- GMP-IVD due diligence inspection Part A
- GMP-IVD due diligence inspection Part B
- Regulatory Control Level Questionnaire of FIND cooperation partner
- Certification of clinical trial sites
Inspections are conducted by trained FIND personnel or subcontracted external experts. An inspection plan must be prepared by the inspector and project leader, and forwarded to the partner that is to be inspected at least 14 days in advance of the inspection.
- Technical due diligence inspection
The purpose of a technical due diligence inspection is to assess the premises, equipment, scientific and technological expertise of the research cooperation partner for the Feasibility phase. The FIND inspector may recommend additional improvements that fulfill FIND requirements.
- Financial due diligence inspection
The purpose of a financial due diligence inspection is to assess a partner’s classification of commercial stage of development, key financials, and associated weaknesses or risks for FIND. Expert examiners, e.g. members of FIND Financial Office or external experts, should be in charge of financial inspections.
- Specimen bank due diligence inspection
The purpose of a specimen bank due diligence inspection is to assess a partner’s capability to host a specimen bank. The premises, equipment, scientific and technological expertise of the cooperation partner should be evaluated. The inspection is mandatory prior to signing a contract with the partner to host a bank.
- GMP-IVD due diligence inspections
The purpose of GMP-IVD due diligence inspections is to assess a partner’s manufacturing capabilities and their compliance with GMP-IVD practices.
GMP-IVD due diligence inspections are separated into two parts: Part A and Part B.
Part A inspection shall be conducted before a manufacturing line of FIND-supported IVD is fully operating. Part A inspection entails a general assessment of the partner’s manufacturing facility to verify compliance with GMP-IVD practices.
Part B inspection shall assess the quality of the complete manufacturing process of a FIND-supported IVD. A Part B inspection tracks inclusion of recommendations from Part A inspection (if any), and assesses GMP-IVD compliance of the FIND-supported IVD manufacturing process. Part B inspection shall be conducted if the first lot of FIND-supported IVDs has been manufactured at the beginning of the Evaluation phase (or Demonstration phase, if Evaluation phase has been bypassed).
Back to top
5. Clinical Evaluation and Demonstration trials
The development of infectious disease diagnostics is critically dependent upon the availability of study populations in endemic countries during clinical development. Consequently, advancing the diagnostics in the FIND disease portfolio through the development pathway requires a solid infrastructure for clinical research. The generation of scientifically sound data and protection of rights of study participants are basic principles in FIND study design for FIND target markets. Studies are named according to the product development phase in which they are conducted.
Feasibility studies are studies intended to validate proof of principle and provide adequate preliminary data to warrant initiation of product development. Primary endpoints are analytical and, in some studies, also operational and clinical test performance. Analytical data, intended to prove that a given method or set of reagents detects the targeted analyte in concentrations and conditions adequate for clinical utility in a completed product, may be obtained during validations in laboratories of research partners. These studies use experimentally prepared research materials, such as dilutions of bacteria or parasites, purified components or archived clinical reference materials. Early operational and clinical performance data can, however, already be collected in settings of intended use, at sites with access to sufficient numbers of specimens from patients being evaluated for the target disease. Feasibility studies may have abbreviated clinical endpoints and limited discrepant result analysis compared to Development or Evaluation studies. Sample or patient numbers are normally not statistically powered to determine clinical sensitivity and specificity with narrow confidence intervals. Nevertheless, results must be sufficiently strong to allow FIND to make a correct go no-go decision for the Development phase and appropriate partner selection. Results of Feasibility studies are judged against targets detailed in the Feasibility Target Specification document.
Development studies are studies intended to validate IVD prototypes designed and developed by manufacturing partners before lock of design. Primary endpoints are analytical, operational, and clinical test performance. Operational and clinical performance data are collected in settings of intended use, at sites with access to sufficient numbers of specimens from patients being evaluated with respect to the target disease. Sample or patient numbers are normally not statistically powered to determine clinical sensitivity and specificity with narrow confidence intervals. Results must be sufficiently strong to allow manufacturing partner the design-lock of diagnostic product and completion of Development phase. Results of Development studies are judged against targets detailed in the Product Specification document.
Evaluation studies are performed on a product that has completed development, and is design-locked and ready for scaled up manufacture. Such studies are intended to produce high quality data for use in registration of the product with national regulatory agencies and must be collected in a manner that conforms to relevant external quality standards. Clinical follow-up of some months might be required to determine clinical specificity and predictive values of the new test in a population of suspects of a disease or disease stage. Results of Evaluation studies are judged against targets detailed in the Product Specification document.
Demonstration studies (“Demonstration projects”) are carried out in the context of a routine clinical services provision, either directly by the Ministry of Health (MOH), e.g., the National Disease Program, or by other agencies working in collaboration with the MOH. Demonstration studies are large studies, with enrollments of up to 10,000 patients, and are intended to provide the evidence that new tests that perform well in controlled settings can have an important medical and public health impact when implemented in programmatic settings. The type of endpoints commonly studied, such as feasible assay implementation, comparative cost between new and old technologies, and impact on speed or accuracy of detection and subsequent patient management, require a substantial clinical and data management infrastructure. A validation phase is required prior to Demonstration studies to prove capability of trial site laboratories to appropriately implement the IVD under local conditions. Target of validation phase is usability of IVD and clinical performance evaluation with a set of well-defined positive and negative human samples (analyzed using gold standard methods). Performance targets must be set by the study coordinator and Demonstration study can only be started if targets have been met.
The results of Demonstration projects are compared against Customer Requirements, as stated by Ministries of Health, the WHO and other international technical agencies, and donors. Data will be compiled, analyzed and presented to WHO for a policy recommendation for the use of these tests in high-burden, low-income countries. In addition, the MOHs of countries that were participating in the Demonstration projects for these new tests may independently make a policy decision on their use.
FIND Office of Regulatory Affairs supports the product launch plan for selected high-burden TB countries. It ensures that all clinical trials are fully compliant with the laws and ethical standards of the countries in which they are taking place. Under national legislation, trials will be planned and conducted in collaboration with the local clinical and laboratory representatives, and trial protocols will be reviewed by an ethical board (or institutional review board, IRB) that is recognized by the legal authorities. Clinical trials are performed according to developed FIND standards in compliance with ISO regulations and guidelines on Good Clinical Practice and Good Laboratory Practice. Shipments of trial materials will follow national importation laws and directives. Regulatory Affairs supports the cooperation partner in the process of test registration in IVD-regulated developing countries.
As sponsor of clinical studies, FIND is responsible for the initiation and the professional conduct of a clinical trial in compliance with established regulations. The FIND Head of Product Evaluation and Demonstration (HPED) and FIND Medical Officer from the Office of Product Evaluation and Demonstration (OPED) are responsible for the planning, direction, data management and data evaluation of all studies under FIND sponsorship and are supported in these tasks by the project leader. The HPED will appoint a qualified FIND study coordinator who has the overall responsibility for a study and who will supervise the organization, direction and reporting of a trial. FIND will manage standardized clinical trial planning for all its diagnostic projects since qualification of trial sites, in particular for Evaluation studies in developing countries, is a prerequisite for generating reliable data on clinical test performance, and the registration or adoption of tests.
Organization of clinical studies, including roles and responsibilities, planning, start of trials, study performance and data management are described in the FIND Clinical Trial Standard.
Back to top
6. Regulatory Affairs
The manufacturer of a FIND-supported IVD is solely and fully accountable for conformity assessment of the IVD as well as for all activities required for product registration under national or regional law. The cooperation partner is responsible for the launch, distribution, service and market vigilance of the diagnostic product in FIND target countries. The partner usually gets help from Regulatory Affairs offices from local affiliates, subcontracted companies or distribution agencies that are responsible for the registration process. If diagnostic tests have been registered and distribution was initiated, the commercial partner is responsible for market vigilance of all products for diagnostic use. The partner has to notify authorized bodies on adverse effects of the IVD and agrees to take responsibility for those activities in the signed contract with FIND.
Any product-related adverse events affecting clinical trials will be reported immediately to the cooperation partner who is responsible for notifying legal authorities and implementing product improvements, as necessary. FIND has a supporting function in the regulatory process.
Back to top
7. Logistics Office and Purchase Orders
The responsibility of the FIND Logistics Office and process of purchase orders is described in the Standard Operating Procedures. In the course of an in-vitro diagnostic test development, FIND’s project leaders and medical officers will partner with clinical trial sites in high-burden countries to evaluate the IVD test specificity and sensitivity in actual local settings. Together the project leader or the medical officer and the trial site collaborator will plan a forecast for IVD consumption that is consistent with the clinical trial protocol. For this, eight steps have been defined:
- Clinical Trial Site request
- Purchase Order draft
- Shipping documents
- Signatures
- Tracking
- Delivery confirmation
- Payment
- Archiving
|
