The FDA is provided guidance to assist sponsors in developing vaccine to protect against global infectious diseases. The guidance focuses on development of licence of vaccines for infectious diseases or conditions endemic in areas outside the United States. It aims to clarify regulatory status and guidance already published for development of these products.
Full guidance given below
Posted in clinical, pre-clinical
Tagged FDA, global, guidance, infectious disease, vaccine development
There are over 20 antiretroviral agents (ARTs) belonging to several classes that have been approved in the European Union. Recent approvals have seen improved tolerability and more convenient dosing regimens thus the therapeutic goal of most patients has changed in recent years as most are now aiming to suppress plasma viral load. However there are still a few patients that do not achieve sustained viral suppression either due to viral resistance or an inability to tolerate certain agents combinations. This changing landscape has pushed the MA towards changing guidance was adopted in 2008. New agents greatly enhance the likelihood that treatment experienced patients can achieve sustained viral suppression and thus the pool of failed patients has been constant dribbling reduced. However new anti-viral therapies are still needed. Existing guidance does not provide a feasible regulatory path the clinical development of such agents.
This concept paper looks at tackling this now complex drug development environment for HIV antiretroviral therapies.
This comprehensive clinical guidance published by nice on colorectal cancer covers the diagnostic investigations that are required, the methodologies that are approved for the staging of colorectal cancer, preoperative management of the primary tumour, colonic stents that can be used in acute large bowel obstruction, treating stage one colorectal cancer, imaging hepatic metastases, outlines approved chemotherapy for advanced and metastatic colorectal cancer, provides follow-up for apparently curative resection and gives background information about bowel function related to the treatment of colorectal cancer.
The guidance covers critical clinical considerations for investigational studies in phase 1 and two clinical trials and phase 3 clinical trials. The guidance makes recommendations for the design of clinical trials conducted under an IND to spot subsequent biological license applications. This is finalisation draft guidance was published in September 2009.
the product discussed in this guidance are therapeutic cancer vaccines intended to result in specific responses to tumour antigens and are intended to treat patients with an existing cancer. These products are traditionally regulated by the Centre for Biological Evaluation Research (CBER) and are referred to as cancer vaccines throughout this document.
The FDA has published this draft guidance in response to international conference on harmonisation of technical requirements for the register duration of pharmaceuticals for human use meetings and publications. This guidance is specific to the requirements of data elements and message specification.
the ICH E2B(R3) message standard is built upon health level III ICSR release free standard. Conceptually this report of information describing adverse events or reactions experienced by an individual patient; the events and reactions can be related to the administration of one or more medicinal products at a particular point in time. The ICSR can also be used exchange other information such as medication errors that do not involve adverse events or reactions.
The FDA sees the guidance as supporting the implementation of software tools for creating, editing, sending and receiving electronic IC SR messages. If you do not see it as a guide pharmacologist practices nor is it intended to explain the underlying scientific or medical issues that support the correlation categorisation or analysis of safety information.
The EMA has published a concept paper inviting input from industry into a proposed update to the guidance on the evaluation medicinal products indicated for treat bacterial infections, to address indication specific clinical data requirements.
this initiative follows several requests were made to the CH MP to provide more detailed guidance on issues such as Pearson selection criteria and primary endpoints including efficacy variables and the timing of assessment outcomes. Specific interest was laid out non-inferiority study designs that would be acceptable to the regulators. A number of enquiries were concerned about the feasibility of achieving superiority endpoints in clinical studies and more guidance was needed to assist companies developing clinical programs that would be feasible and meet with regulatory approval in this area.
In response to this the EMA held a number of workshops and are now looking to make changes to the guidance to meet these issues.
Posted in clinical, Uncategorized
Tagged data requirements, guidance, Treatment of bacterial infections
The FDA publishes guidance that is intended to assist applicants and reviewers in drafting the warnings and precautions, contraindications, and boxed warning sections of labelling, as described in the final rule amending the requirement for the content and format of labelling for human prescription drugs and biological products.
The guidance is a set of recommendations is intended to help ensure the labels are clear, useful, informative and to the extent possible consistent in context and format.
Tagged contraindications, labelling, precautions, warnings
The FDA as published in appendix to its guidance on the electronic transmission of individual case safety reports (ICRS) which is an implementation guide for international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use and to electronic message of the transmission of individual case safety reports.
The appendix is intended to assist reports and recipients in implementing the systems with a special focus on the recommendations come version back and forth between previous standards.
full text here
This document is an appendix to the guide for implementing the “International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) M2: Electronic Message for the Transmission of Individual Case Safety Reports (ICSRs).”
This Appendix is intended to assist reporters and recipients (including pharmaceutical companies, authorities and non-commercial sponsors) in implementing systems with special focus on the recommendations for conversion back and forth between the previous standard, i.e., E2B(R2) and this new one, i.e., E2B(R3).
The evolution of the guideline, from E2B(R2) to E2B(R3), has the consequence that ICSRs cannot be perfectly converted from one standard version to the other (either backwards or forwards). This document presents the recommendations for conversion agreed within ICH so as to provide a reference to system providers, and a common understanding on the way to convert ICSRs and ICSR acknowledgments (ICSR ACKs) between E2B(R2) and E2B(R3).
The FDA has published draft guidance for implementing ICH requirements for electronic transmission of individual case safety reports (ICSRs).
This implementation guide was jointly developed by the ICH E2B (R3) and the M2 expert working groups, and provides the business requirements and technical content and implementation of the ICH regulation.
Its purpose is to support the implementation of software tools for creating, editing, sending and receiving electronic ICS are messages. It is not intended as a guide to pharmacology and practices.
This document is a guide for implementing ICH1 requirements for the electronic transmission of Individual Case Safety Reports (ICSRs) according to the ICH E2B(R3) message standard. This Implementation Guide was jointly developed by the ICH E2B(R3) and M2 Expert Working Groups (EWGs), which were reconstituted as the ICH E2B(R3) EWG in November 2010. The E2B(R3) EWG provided business requirements and the M2 EWG provided technical contents for this Implementation Guide.
The ICH E2B(R3) message standard is built upon the Health Level 7 (HL7) ICSR Release 3 standard (or HL7 ICSR R3). The HL7 ICSR R3 standard is a particular message based on the HL7 Version 3 messaging standard (or HL7 V3), a broader platform for health care information transfer. Please see section 2.2 for an explanation of HL7 versions.
Conceptually, an ICSR is a report of information describing adverse event(s) / reaction(s) experienced by an individual patient; the event(s)/reaction(s) can be related to the administration of one or more medicinal products at a particular point in time. [1] The ICSR can also be used for exchange of other information, such as medication error(s) that do not involve adverse events(s)/reaction(s). The information for the report is provided by a primary source, although, depending on regional requirements, new information, or for practical or logistical issues, a given ICSR can be updated or retransmitted by either the initial sender or a 3rd party.
The ICH requirements for implementation of the ICSR focuses on medicinal products and therapeutic biologics for human use, although regional applications of the ICSR can include a wider scope, such as for Pharmacovigilance related to vaccines, herbal products, cosmetics, veterinary products or medical devices. The primary ICH application is for the exchange of pharmacovigilance information between and among the pharmaceutical industry and regulatory authorities.
This guide is intended to support the implementation of software tools for creating, editing, sending and receiving electronic ICSR messages. It is not intended as a guide to pharmacovigilance practices nor is it intended to explain the underlying scientific or medical issues that support the collation, categorisation or analysis of safety information. It is also not intended to explain the rationale that underlies the content requirements for safety reporting – the regulatory requirements and harmonised practices that determine what elements are required or optional and what types of information must fill those elements.
This is a technical implementation guide. It is meant to be consulted by system developers, IT professionals, system implementors and system users who need to understand the requirements for constructing and using valid electronic messages to transmit ICSRs. It provides a pathway to support the development of forms and user interfaces and the determination of pick lists in tools. It provides the technical requirements to design style sheets, data transformations and coding of exported messages. It should not be interpreted as a guidance or recommendation for any particular database technology or software platform, other than the requirement to generate valid XML code according to the standard outlined in this Implementation Guide.
Posted in clinical
Tagged CH, electronic transmission, ICH E2B(r3), ICSR, Individual Case Safety Reports
The FDA estimates that around 550 to 650 surgical fires occur each year in the United States, some causing serious injury, disfigurement and even death. Despite the fact that the root cause of surgical fires is well known and understood many and healthcare organisations have developed tools, rules, and processes to reduce the effect of fire, the incidence of fires is not falling. To supplement these locally developed rules and procedures the FDA and its partners are launching “preventing surgical fires initiative” in order to help increase awareness of the factors that contribute to surgical fires, disseminate surgical fire prevention tools, and promote the adoption of risk reduction practices.
find full details here
As the number of available techniques to facilitate the study of human genomics has led to an exponential increase in investigation into genomic bio markersthe diagnosis of specific diseases. The AMA has decided that a guidance would be required to assist companies in implementing these technologies into clinical drug development.
These techniques are frequently used patient selection stratification or treatment strategies of patient groups, and the EMA is concerned the appropriate steps are not been taken hence the publication of this guidance.
full text here
The availability of techniques that facilitate study of the human genome has led to an exponential increase in investigation into genomic biomarkers (GBMs) for diagnosis of specific diseases, as a marker of response to treatment or of prognosis. Theoretically genomic BMs should offer the advantage of improved specificity and reduction of heterogeneity that is an integral part of phenotypic population grouping. This is very attractive in drug development because of their potential ability to reduce drug attrition and to reduce overall developmental costs, that are achieved through improved understanding of the mechanism of drug action, predict adverse events to individual drugs or as a group effect (e.g. CYP poor metabolisers), and use of novel development strategies in pre-clinical and clinical phases.
In clinical drug development, GBMs may aid and influence a wide range of areas: patient selection, stratification of treatment strategies or patient groups, early evaluation of treatment effect including adverse reactions, and prognosis. There is opportunity for the GBMs to be used for pre-defined subgroup analysis or to enable novel trial designs that might not be possible otherwise due to heterogeneity of clinical characteristics.1,2 GBMs could also play a valuable role in the risk management strategies including risk minimisation by aiding a priori identification of patients susceptible to develop severe adverse effects (e.g. HLA B*- 5701 and use of Abacavir).
While a number of these aspects are discussed in many publications in the recent years, specific aspects relating to drug development and discussion on regulatory considerations have lagged behind. The intention of this paper is therefore to provide an evidence based consideration of GBM related issues from a regulatory viewpoint. Mention is also made of co-development of a GBM diagnostic test for use with a medicinal product.
The principles established in the reflection paper are based on the experiences gained from the evaluation of dossiers within the EU regulatory processes —including marketing authorisation applications reviewed by CHMP, the scientific advice documents and additionally, the voluntary genomic data submission meetings (briefing meetings) at the Pharmacogenomic Working party (PGWP) over the last several years. It is expected that these principles guide both industry and the assessors in the evaluation of such biomarkers in relation to the qualification process in the context of clinical development (BM qualification in EU) and the assessment of benefit: risk balance of medicinal products or selection of the relevant target population. The paper should also be read in conjunction with other relevant guidelines listed at the end of the documents under section “Other aspects”.
Development of GBMs and diagnostic tests may involve additional development of tests (companion diagnostics) or specific kits (platforms) to detect for the presence or absence of the GBM. Issues relating to these are outside the scope of this paper but a short discussion is included. The readers are referred to appropriate guidelines/ papers for details (see section on other aspects).
This guideline developed by the EMA is to assist companies in providing the documentation that is required for when making and marketing authorisation application for recombinant human plasma derived factor 9 product. Specifically the product being used to treat patients the prevention of bleeding in haemophilia B. The guidance covers the clinical investigations to be conducted the prick and post marketing authorisation, this guide is also provides information when there is a significant change in the manufacturing process.
full text here
This guideline describes the information to be documented when an application for a marketing authorisation for recombinant or human plasma-derived factor IX products is made for use in treatment and prevention of bleeding in patients with haemophilia B. The guideline covers clinical investigations to be conducted pre- and post-marketing authorisation. Guidance is also provided for authorised products where a significant change in the manufacturing process has been made.
Timeline history of guideline: The original Note for Guidance on Clinical Investigation of Human Plasma Derived FVIII and FIX Products (CPMP/BPWG/198/95) came into operation on 14 February 1996. The first revision (CPMP/BPWG/198/95 Rev. 1) came into operation in April 2001. The original Note for Guidance on Clinical Investigation on Recombinant FVIII and FIX Products (CPMP/BPWG/1561/99) came into operation in April 2001. Draft revisions of CPMP/BPWG/1561/99 and CPMP/BPWG/198/95 were released for public consultation in July 2007. Following this consultation, it was decided to reorganise the guidance to have separate documents: The Guideline on clinical investigation of recombinant and plasma derived factor VIII products (EMA/CHMP/BPWP/144533/2009) and the Guideline on clinical investigation of recombinant and plasma derived factor IX products (EMA/CHMP/BPWP/144552/2009).
EMA considers that there is sufficient research data available to support premenstrual dysphoric disorder (PMDD) at a diagnostic entity.
It is considered to have considerable public health impact in a small subpopulation of menstruating women. This guideline is to provide guidance on the clinical evaluation of products to treat this patient group.
full text here
There are substantial research data available to support premenstrual dysphoric disorder (PMDD) as a diagnostic entity of a severe form of premenstrual disorder, which causes clinically relevant functional impairment and requires treatment. It is considered a disorder with substantial clinical and public health impact in a [small] subpopulation of menstruating women. The aim of this guideline is to provide guidance for the evaluation of medicinal products in the treatment of PMDD.
The present document should be conceived as general guidance, and should be read in conjunction with other applicable EU and ICH guidelines (see Section 3)..
Up to 70-90 % of women of reproductive age have one or more signs of physical discomfort or emotional symptoms in the premenstrual, i.e. luteal phase of their menstrual cycle. About 20-40 % of menstruating women have premenstrual syndrome (PMS) and experience luteal phase symptoms that are bothersome. A smaller number, up to 8 %, experience more severe symptoms, which lead to substantial distress or functional impairment and are referred to as premenstrual dysphoric disorder (PMDD) (10, 11, 13, 14, 23, 38, 39, 42). Although PMDD, like PMS includes physical symptoms, it always involves a worsening of mood that interferes significantly with the woman’s quality of life. The burden of illness of PMDD results from the severity of luteal phase symptoms, the chronicity of the disorder and the impairment in work, relationships and activities.
In the last decades a very broad diagnostic concept of the premenstrual disorders PMS and PMDD has been used in clinical research, which produced different diagnostic criteria and highly heterogeneous study populations.
Recent advances and research data improved the knowledge on diagnosis, frequency, pathophysiologic mechanisms, and treatment options in PMDD. This led to treatment recommendations by learned societies for PMDD.
The EMA believes that clinical evaluations of paying me to be refined in order to better reflect the different kinds of pain been studied. Due to the subjective nature of pain and the problems associated with correct diagnosis patients are frequently undertreated acute and chronic situations. Whilst Noiceptive and neuropathic pain have been internationally defined the experience on clinical development has not been large.
The EMA believes the different types of pain may have different pathophysiological mechanisms and pathways which should be considered in the clinical development of new analgesic agents, and the proposed models to evaluate treatment efficacy should be updated in line of the experience gained during the past years.
full text here
Pain is the most common symptom for which patients seek medical attention. Although there is no exact definition it has been defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (International Association for the Study of Pain (IASP). Due to the subjective component of pain and the problems associated with a correct diagnosis patients are frequently undertreated for acute and chronic situations.
Nociceptive and neuropathic pain has been internationally defined. Nociceptive pain can be defined as the process by which intense thermal, mechanical, or chemical stimuli are detected by a subpopulation of peripheral nerve fibers, called nociceptors whereas neuropathic pain can be defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. In addition, pain can be of mixed origin (e.g. cancer pain), thus justifying that the 2 current guidelines are merged in a unique document. When current guidelines on nociceptive and neuropathic pain were written, the experience on clinical development was not large.
The different types of pain which may have different pathophysiological mechanisms and pathways should be considered in the clinical development of new analgesic agents, and the proposed models to evaluate treatment efficacy should be updated in line of the experience gained during the past years.
Fibromyalgia is a complex disease with clinical features other than pain and should be dealt with in a separate document.
In the current EMA guideline on similar biological medicinal products containing biotechnology derived proteins as active substances, nonclinical and clinical issues lays down the requirements of such products to determine its similarity to one another. This guidance came into effect in June 2006, however since then several by a similar products have come to the market and the number of guidance is in this area has increased significantly and the regulatory framework is becoming wider.
The EMA considers it necessary to update these guidance and bring together a number of issues into a single document. In order to tackle the complex issues that are arising. And to allow for the WHO guidelines on evaluation of similar biotherapeutic products. And also to be compliant with the Three R principals (replacement, reduction and refinement) with regard to the use of animal experiments.
full text here
The Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (EMEA/CHMP/BMWP/42832/2005) lays down the nonclinical and clinical requirements for a biological medicinal product claiming to be similar to another one already marketed. This guideline came into effect in June 2006. Since then several biosimilar products
have come into the EU market, the number of scientific advices given by the CHMP on the development of biosimilar products has increased significantly and the regulatory framework is becoming wider, e.g. the draft guideline of the biosimilar monoclonal antibodies is being finalised. .An increasing number of biosimilar products are under development, especially biosimilar monoclonal antibodies. The development of more complex biosimilar medicinal products is challenging, and several issues in the development are under re-evaluation. These include the selection of relevant species for
non-clinical studies, need for clinical equivalence studies and other issues of the design of the pivotal clinical studies, role of biomarkers, amount of immunogenicity data needed, and the possibility to
extrapolate to other indications. The WHO Guidelines on Evaluation of Similar Biotherapeutic Products with detailed recommendations on clinical development were published in October 2009. In addition,
the EMA is emphasizing the need to follow the 3 R principles (replacement, reduction and refinement) with regard to the use of animal experiments. All these factors suggest revising the current guideline.
The current regulatory requirements quality, nonclinical and clinical development of influenza vaccines are currently stated in several regulatory documents. These guidelines were drafted and appointed a different time points over several years before the onset of the major pandemics in 2009 - 2010.
The EMA has recognised a need to update the guidance of requiring the manufacturing, nonclinical and clinical development of complaints of vaccines. Especially in the light of novel vaccine technologies such as recombinant proteins, viruslike particles (the LPs) DNA or live viral vectors.
For these reasons the EMA may has issued this concept paper.
full text here
Regulatory requirements for the quality, non-clinical and clinical development of influenza vaccines are
currently stated in several documents including multidisciplinary guidelines such as
EMEA/CPMP/4986/03, CHMP/VWP/263499/06, the Note for guidance on harmonisation of requirements
for influenza vaccines CPMP/BWP/214/96 and the Guideline on dossier structure and content for
pandemic influenza vaccine marketing authorisation application (EMEA/CPMP/VEG/4717/03 rev. 1).
These guidelines were drafted and adopted at different time points and over several years before the
onset of the 2009-2010 influenza pandemic and each addresses one of seasonal influenza vaccines,
pre-pandemic or pandemic vaccines.
The need to update the available guidelines regarding the manufacturing, non-clinical and clinical
development of influenza vaccines was recognised during and following the 2009-2010 influenza
pandemic. More recently, issues encountered and experience gained during requests for CHMP
scientific advice and the processing of several applications for marketing authorisation of influenza
vaccines have underlined the desirability of updating the existing guidelines. In addition, it is
anticipated that novel influenza vaccines could be based on e.g. recombinant proteins, virus-like
particles (VLPs), DNA or live viral vectors and there is a need to consider the regulatory expectations
that would apply to such products.
Although current and future influenza vaccines may vary in nature and composition they all aim to
prevent clinically manifest influenza by means of eliciting a protective immune response. Therefore the
development of a single consolidated guidance document on the quality, non-clinical and clinical
requirements for influenza vaccines seems to be both feasible and appropriate.
full text here
This question-and-answer document has been published with the goal of replacing the existing procedural advice for validation of new marketing authorisation application-extension/variation application and compliance check with an agreed PIP (paediatric investigational plan).
the compliance check is an important part of the PIP program and as a key part of the drug development program in Europe, and this document is aimed at assisting people to understand procedures.
questions include:
Posted in clinical
Tagged application, compliance, paediatric investigational plan, PIP, waiver
Two pilot programs of collaboration on inspections between European medicines agency and its international partners in United States and Australia have been conducted successfully. The two programs focused on collaboration between international regulators for quality and safety.
Joint inspections on good clinical practice were undertaken in a large number of clinical programs, as well as joint inspections of active pharmaceutical ingredients manufacturing plants.
All agencies have agreed that the programs have been a success and will continue on this collaborative approach in future. This is clearly start of international recognition between the agencies inspection standards, which should have positive effects of mutual recognition and reduce the regulatory burden of companies operating internationally in our industry.
Full Text Here
Two pilot programmes of collaboration on inspections between the European Medicines Agency (EMA) and its international partners in the United States and Australia have concluded successfully, according to two reports published today. The two programmes focus on increasing international regulatory collaboration among the regulatory agencies so that drug quality and safety can be enhanced globally.
The report on the joint good clinical practice (GCP) inspection pilot programme details the success of information-sharing and collaboration on inspections relating to clinical trials. Under the joint GCP inspection pilot, the EMA and the US Food and Drug Administration (FDA) exchanged more than 250 documents relating to 54 different medicines and, in conjunction with the GCP inspectors of the EU Member States, organised 13 collaborative inspections of clinical trials. This lays the foundation for a more efficient use of limited resources, improved inspectional coverage and better understanding of each agency’s inspection procedures. It demonstrates how the agencies can work together to improve the protection of participants in clinical trials and better ensure the integrity of data submitted as the basis for drug approvals.
The report on the joint active pharmaceutical ingredients (API) inspections pilot programme details the success of information-sharing and collaboration on API inspections among the participating authorities (EMA, France, Germany, Ireland, Italy, United Kingdom, EDQM, FDA and Australia’s Therapeutic Goods Administration (TGA)). Over the course of the 24-month pilot phase, the participants shared their surveillance lists and found 97 sites common to all three regions, resulting in the exchange of nearly 100 inspection reports and in nine joint inspections.
Both pilots involved the exchange of considerable amounts of information and the establishment of inspections carried out jointly by the agencies. This led to increased levels of understanding between the agencies, and a greater number of inspections of value to more than one authority.
Based on the positive experience in the two pilots, the agencies have agreed to continue with their collaboration on inspections, taking into account the experiences and lessons learned during the pilot phases.
Good Clinical Practice (GCP) is the quality standards to which we all work when managing clinical trials. ICH GCP as we all know is the overriding framework that we worked up. And a section 5.1 points out sponsors need to implement and maintain quality assurance and quality control systems to ensure the safety and well-being of trial subjects are protected as well as their legal and ethical rights. the EMA have considered that the number of clinical trials with quality issues is on the increase and our looking to develop some guidance to help sponsors put together risk-based quality management systems within clinical trials this reflection paper is a summary of that thought.
full text here
Good clinical practice (GCP), is a set of internationally recognised ethical and scientific standards for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials.
ICH GCP requires in Section 5.1, that the sponsor implements and maintains systems for quality assurance and quality control; similarly the Article 2 of the GCP Directive 2005/28/EC, , requires the implementation of procedures necessary to secure the quality of every aspect of the trial. The aim of those quality management measures is to provide assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The same requirements apply to Contract Research Organisations (CROs), vendors or other service providers to whom the sponsor has delegated any trial related duties and functions of the sponsor. However the sponsor remains responsible for the quality of the trial. The ICH GCP was finalised in 1996 when clinical research was largely paper based, but the available technology and the approach to the conduct of clinical trials has evolved considerably in the meantime.
The key elements of the quality system include:
Documented procedures being developed, implemented and kept up-to-date
Training of sponsor personnel as well as of the personnel in affiliates, at partners and at trial sites
Validation of computerised systems
Monitoring of trial sites and technical facilities on-site or by using centralised monitoring techniques
Data management and quality control
Internal and external audits performed by independent auditors
The current manner in which these quality systems are implemented by sponsors and their agents (CROs etc) are generally acknowledged to be costly and time-consuming, and constitute a major proportion of the cost of development of medicines.
Implementing these processes can be and often is successful in achieving a good quality clinical trial. However it is expensive and there remain too many trials in which avoidable quality problems arise as evidenced for instance by the nature and extent of findings, identified by European GCP inspectors during inspections. The combination of these findings and the very high cost of the processes involved strongly suggest that current approach to clinical quality management is in need of review and reorientation.
A scalable and proportionate approach is required in order to cover the needs of academic researchers, Small and Medium Enterprises (SMEs) and large multinational pharmaceutical organisations.
Sponsors are expected to cope with this challenge and to move towards a more systematic and risk based approach. There is a need to find better ways to make sure that limited resources are best targeted to address the most important issues and priorities, especially those associated with predictable or identifiable risks to the wellbeing of trial subjects and the quality of trial data.
ICH-GCP, e.g. in respect to auditing, already underlines that the sponsor’s audit plan and procedures for a trial audit should be guided by the importance of the trial for submissions to regulatory authorities, the number of subjects in the trial, the type and complexity of the trial, by the level of risks to the trial subjects, and any identified problem(s). Similarly the GCP requirements for monitoring indicate that the sponsor should determine the appropriate extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial.
With the implementation of ICH Q9 guideline2 as GMP Annex 20 in March 2008, Quality Risk Management has become an accepted standard. This concept can be adapted and described for clinical research with medicinal products.
Thus, the purpose of this reflection paper is to facilitate the development of a more systematic, prioritised, risk-based approach to quality management of clinical trials, to support the principles of Good Clinical Practice and to complement existing quality practices, requirements and standards.
The activities of other groups in this area (e.g. ADAMON3, ECRIN, OPTIMON8, MRC/DH/MHRA joint project: Risk Adapted Approaches to the Management of Clinical Trials4 and the Organisation for Economic Co-operation and Development (OECD)), the FDA CTTI (Clinical Trial Transformation Initiative), CTFG, GCP IWG and the principles of ICH Q8 Pharmaceutical Development5, Q9 Quality Risk Management2 and ICH Q10 Pharmaceutical Quality System6 have been taken into account in developing this paper.
Posted in clinical
Tagged clinical trial, Quality Management, Quality Tolerance Limit, Risk Control, Risk Management
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