09.01.2015

Clinical trial authorisation definition

Regulatory consultancy services cover all steps of the process, from clinical trial planning to post-approval marketing authorisation maintenance. 27 November, Brussels – Clinical trials are conducted globally and there is increasing international competition in this area because clinical research creates jobs, drives academic excellence and delivers innovative medicines for patients.  Improving the attractiveness and competitiveness of Europe as a prime location for clinical research was a key driver for the revision of the EU clinical trial legislation, which aimed to reduce unnecessary red tape whilst preserving, the quality and safety of clinical trials.
The European legislators are expected to reach a compromise on the Clinical Trials Regulation before Christmas. The longer the regulatory process takes to approve a clinical trial or process regulatory procedures around it, the greater the cost of the trial.
For the Commission to ensure support for EU Member States during the implementation phase to make certain the timelines in the legislation are met. EFPIA Director General Richard Bergstrom stated: “The timelines set out by the Commission are achievable – we can look to Belgium and the United Kingdom as examples for best practice.
Alastair Kent OBE, President of EGAN, said: “It is important for European patients that research happens here in Europe. Miriam Gargesi, Director of Healthcare at EuropaBio stated: “EuropaBio recognises the need for competitive assessment timelines to ensure an attractive regulatory environment for clinical research. Sara Osborne, Head of Policy at Cancer Research UK: ““Clinical research funded by organisations like Cancer Research UK - which is entirely supported by generous public donation - is crucial to improve our understanding of existing treatments as well as developing new ones. The Patients Network for Medical Research and Health (EGAN) is an alliance of both national genetic alliances and European disease specific patient organisations with a special interest in genetics, genomics and biotechnology. EuropaBio is the European Association for Bioindustries, bringing together bioscience companies from all fields of research and development, testing, manufacturing and distribution of biotechnology products. The Association of Clinical Research Organizations (ACRO) represents companies that provide a variety of specialized services that support the development of new pharmaceuticals, biologics and medical devices. Cancer Research UK is the world’s leading charity dedicated to saving lives through research. In the present scenario, countries have different regulatory requirements for approval of a new drug. The new drug approval is of two phase process - the first phase for clinical trials and second phase for marketing authorization of drug. Even after the approval of new drug, government should monitor its safety due to appearance of some side effects, when it is used in larger population.
The Food and Drug Administration (FDA) is responsible for protecting and promoting public health. In European Union (EU), the medical products were approved for marketing at the National level initially. Similarly, the drug approval process in European countries is also accomplished in two phases: clinical trial and marketing authorization. After completing of all three phases of clinical trial, marketing authorization application is filed including all animal and human data, its analyses, as well as pharmacokinetics, manufacturing and proposed labelling.
The Committee for Human Medicinal Products (CHMP) evaluate the applications received by the EMEA. In order to obtain marketing authorizations in several member states, the centralised procedure is not mandatory; in such case the decentralized procedure is to be used.
This type of authorization is granted on country-by-country basis by the competent authorities, in each member state. The mutual recognition procedure (MRP) is similar to the de-centralized procedure with some differences. In 1963, for the management of new drugs, Chinese Ministry of Health planned drug regulation.
The Drug Administrative Law authorizes the State Food and Drug Administration (SFDA) to approve new drugs for marketing.
In the history of drug regulatory system in Australian, thalidomide disaster was a key factor. Any person seeking approval of a new drug in Australia should first file a clinical trial application for conducting human studies.
The Drug and Cosmetic Act 1940 and Rules 1945 were passed by the India's parliament to regulate the import, manufacture, distribution and sale of drugs and cosmetics.
An application to conduct clinical trials in India should be submitted along with the data of chemistry, manufacturing, control and animal studies to DCGI. Some counties have two review processes as normal review process and accelerated review process as in USA, China etc. Generally, the drug approval process comprised mainly the two steps, application to conduct clinical trial and application to the regulatory authority for marketing authorization of drug. IND-Investigational New Drug, DCGI-Drug Controller General of India, CDSCO-Centre for Drug Standards Control organization.
Dulichand studied B.Pharmacy from Guru Jambheshwar University of Science and Technology, Hisar. The Centralised Procedure is administered by the European Medicines Agency (EMEA) in London. The detailed guidelines on how to apply for Marketing Authorisation of medicinal product via the Centralised Procedure is available on the EMEA website, particularly in the document outlining Pre-submission Guidance.
The majority of authorisations for generic medicines are granted through the Mutual Recognition Procedure and the Decentralised Procedure.
Since the introduction of the DCP, the MRP is mainly used for extending the existing marketing authorisation to other countries in what is known as the "repeat use" procedure. The detailed guidelines on how to apply for Marketing Authorisation for a medicinal product via the Mutual Recognition Procedure and the new Decentralised Procedure are also available on the Heads of the Medicines Agencies website, particularly under the CMD(h) (Coordination Group for the Mutual Recognition and the Decentralised Procedure) section.
I hope the information you provided above will be of great help in clarifying all the doubts about procedure for applying patent. I would like to know, apart from this, what related information should be known for a student who wish to join regulatory affairs as per the industry needs?? For a better understanding of the generic drug approval, one must be clear about the drug development process. The following section provides information on the procedures for the submission of applications for clinical trial. After the conforming the receipt of the documents, different periods apply for the evaluation of different medicinal products by the competent authority pursuant to the GCP regulation. The documents will be checked for formal conformity within 10 days after receipt of the clinical trial authorisation request at the PEI.
If the request is without formal non-conformities, a confirmation of receipt will be sent to the applicant, and the day after the receipt at the PEI shall be the first day of the evaluation of the content by the PEI. After the evaluations of the contents of the request, the applicant will either be notified of the grounds for non-acceptance, or, if no such grounds have been found, the approval certifcate.
If grounds for non-acceptance were communicated, the applicant shall be granted a period of 90 days to answer these grounds by amending the request. The overview shows the average processing periods of the requests for clinical trial authorisations. The target periods refer to periods granted to applicants and the PEI for the individual stages of the request procedure pursuant to the GCP regulation (German Ordinance on GCP). The value of the average of the total period (valid application up to decision) represents the total processing period of the product group from the date of receipt of the valid application up to the decision date, i.e.
The table represents the percentages of notifications of grounds of non-acceptance by product group and by the parts of the dossier quality, preclinical data, clinical data, viral safety, and statistics, if grounds for non-acceptance are raised. The Paul-Ehrlich-Institut is an Agency of the German Federal Ministry of Health.Its research and control activities promote the quality, efficacy and safety of biological medicinal products.
EFPIA, EuropaBio, ACRO, CRUK & EGAN call on all parties to bear the drivers of this legislative revision in mind and take the steps needed to grow EU clinical research. Higher costs can result in fewer trials being run, reducing our ability to understand treatments better.
We want to see a proportionate approach to regulating clinical trials that will foster the innovation that is necessary to solve our unmet health needs.
Through its direct membership of 33 national associations and 40 leading pharmaceutical companies, EFPIA provides the voice of 1,900 companies committed to researching, developing and bringing new medicines to improve health and quality of life around the world. It has 56 corporate members, 14 associate members and Bio Regions and 19 National Biotechnology Associations- representing some 1800 small and medium sized enterprises across Europe. Our groundbreaking work into preventing, controlling and curing all types of cancer has seen survival rates double in the last 40 years. In general, a drug approval process comprises of various stages: application to conduct clinical trials, conducting clinical trials, application to marketing authorization of drug and post-marketing studies.
The single regulatory approach for marketing authorization application (MAA) of a new drug product applicable to various countries (on the basis of single dossier) is utmost difficult. Firstly, non-clinical studies of a drug are completed to ensure efficacy and safety, and then application for conduct of clinical trials is submitted to the competent authority of the concerned country. The interactions with other drugs, which were not assessed in a pre-marketing research trial and its adverse effects (in particular populations) should also be monitored[3].
Like general drug approval process, FDA's new drug approval process is also accomplished in two phases: clinical trials (CT) and new drug application (NDA) approval[7].
A clinical trial application (CTA) is filed to the competent authority of the state to conduct the clinical trial within EU.


In view of the applicant's preference, CHMP contracts out assessment work in one of the member states (the "rapporteur"). An application is submitted to competent authorities of each of the member states, where a marketing authorization is to be sought.
Products only intended for one market and not obliged to use the centralized procedure[19]. The mutual recognition procedure is applicable to medicinal products which have received a marketing authorization in any member state whereas the decentralized procedure is applicable to those products which were never approved in any member states of the European Union. The China's State Pharmaceutical Administration in collaboration with Ministry of Health, in 1979, published the New Drug Management Regulations (no need to conduct systematic scientific experiments on new drugs). The new drug registration process also consists of the clinical study application and the new drug application. In 1948, the first advisory committee to review drugs was set up and further in 1964, the first Commonwealth advisory committee in Australia was established. The Central Drugs Standard Control Organization (CDSCO), and the office of its leader, the Drugs Controller General (India) [DCGI] was established.
The date regarding the trial protocol, investigator's brochures, and informed consent documents should also be attached.
In some countries, only a single body regulates the drugs and responsible for all regulatory task such as approval of new drugs, providing license for manufacturing and inspection of manufacturing plants e.g. The new drug approval process of various countries is similar in some of the aspects whereas it differs in some aspects.
Stringer S., "What Has Been Happening With Over-the-Counter Drug Regulation" Food and Drug Law Journal. Ghalamkarpour A., Marketing Authorization Procedures in the European Union - Making the Right Choice (2009). It consists of a single application which, when approved, grants marketing authorisation for all markets within the European Union. Under MRP, the assessment and marketing authorisation of one Member State, (the "Reference Member State") should be "mutually recognised" by other "Concerned Member States". It is applicable in cases where an authorisation does not yet exist in any of the EU Member States. Clinical research is an essential part of the development process but it is also the lengthiest and most expensive.This review looks at the steps needed to complete this process in the European Union (EU) and describes the rigorous regulatory framework involved in clinical research. The periods referenced here are not total periods for the processing of the requests but solely periods for the evaluation of the content of the documents by the CA. Formal non-conformities will be communicated to the applicant within 10 days and must be answered by the applicant within 14 days.
After submission of the amendment, the PEI shall have a period of 15 or 30 days, depending on the medicinal product, to evaluate the amendment. It is imperative to build on Europe’s innovative edge – not just for competitive reasons, but because innovation is the tool needed to deliver new and improved medicines to patients. The pharmaceutical industry invests 30 billion on research and development per year in Europe and directly employs 700,000 people including 116,000 in R&D units in Europe. Through its member companies, ACRO helps improve the quality, efficiency and safety of biomedical research. Every country has its own regulatory authority, which is responsible to enforce the rules and regulations and issue the guidelines to regulate the marketing of the drugs.
Therefore, the knowledge of exact and detailed regulatory requirements for MAA of each country should be known to establish a suitable regulatory strategy [1]. In 1906, Congress passed the original Food and Drugs Act, which require that drugs must meet official standards of strength and purity[4].
FDA approval process begins only after submission of investigational new drug (IND) application. The primary aim of this procedure was to create a united standard for product review among national regulatory authorities.
The information like quality, efficacy, safety, administrative information shall be submitted and a list of all Concerned Member States (CMSs) and one member state to act as Reference Member State (RMS). In view of protecting the public health and promoting the economic developments in pharmaceuticals, the first comprehensive Drug Administrative Law was framed in 1985.
The Provincial Drug Administration Authorities (PDAAs) should organize the works of the formal review of submitted materials i.e. A copy of the application must be submitted to the ethical committee and the clinical trials are conducted only after approval of DCGI and ethical committee.
Similarly, the format used for the presentation of dossier submitted for approval of drug is also different. In most of the counties, sponsor firstly files an application to conduct clinical trial, and only after the approval by the regulatory authority, the applicant conducts the clinical studies and further submits an application to the regulatory authority for marketing authorization of drug. This procedure is obligatory for high-tech and biotechnology-derived products, for products used for the rare diseases (so called: orphan products), and for products used for treating AIDS, cancer, neurodegenerative disorders and diabetes, as well as for auto-immune and viral diseases since May 2008. Identical dossiers are submitted in all Member States where a marketing authorisation is sought.
Depending on the period which the applicant takes to answer to the possible grounds of non-acceptance, the actual times vary considerably. Towards this end, we strongly support the path set out by the Commission as well as the European Parliament in ensuring competitive timelines for these authorisations, and urges the Council to support this approach moving forward.
ACRO member companies employ approximately 100,000 professionals worldwide and annually conduct more than 11,000 clinical trials involving nearly two million participants in 115 countries. This article will focus the similarities and differences in drug approval process of various regulatory bodies. These studies are performed to ensure the efficacy, safety and optimizing the dose of drug in human beings. However, in 1937, due to sulphanilamide tragedy, the Federal Food, Drug and Cosmetic Act (of 1938) was enacted and added new provisions that new drugs must be shown safe before marketing. The IND application should provide high quality preclinical data to justify the testing of the drug in humans. The EU Commission requests comments from other member states, if a positive opinion from CHMP is received. A draft assessment report on the medicinal product is prepared and the CMSs and the RMS validate the application within a time frame of 14 days. The evaluation of application by RMS can be taken within 90 days instead of 120 days (in decentralized procedure)[20].
This law was amended in 1999 by two additional provisions for new drug approval and provisions for new biological product approval.
In response of lacking control over locally manufactured products, the Therapeutic Goods Act was changed in 1989 and the Therapeutic Goods Administration (TGA) was created [26].
In the latter scheme, application is directly submitted to the Human Research Ethics Committee (HREC) which assesses the validity of design of clinical trial, its ethical acceptability, approval, safety and efficacy of the drug as well. Schedule Y provides the guidelines and requirements for clinical trials, which was further revised in 2005 to bring it at par with internationally accepted procedure. However in some counties all tasks are not performed by a single regulatory authority, such as in India, this responsibility is divided on Centralised and State authorities. In some countries like as in USA, EU, and Japan , it is mandatory that the dossier prepared in CTD format, however, in some countries it is optional such as in India. In all countries, information submitted to regulatory authorities regarding the quality, safety and efficacy of drug is similar; however, the time, fee and review process of clinical trials and marketing authorization application differs. This procedure may be also used for authorisation of products with new active substances and for all other products bringing therapeutic or scientific progress and which are important for patients and animals at the Community level. A Reference Member State, selected by the applicant, will prepare draft assessment documents and send them to the Concerned Member States. Compliance with them ensures the rights, safety, and wellbeing of clinical trial participants, consistent with the principles of the Declaration of Helsinki[3]; and that the clinical trial data are credible. After the completion of clinical studies of the drug, then an application to the competent authority of the concerned country for the approval of drug for marketing is submitted. Further, in 1962, the Kefauver-Harris Amendment Act was passed which require that manufacturers must prove that drug is safe and effective (for the claims made in labelling)[5,6]. Almost 85% of drugs are subjected to clinical trials, for which IND applications are filed.
The purpose and phases of clinical trials are similar as specified in FDA drug approval process[13]. The RMS prepare draft summary of product characteristics, labeling and package leaflet within 120 days. After the grant of marketing authorization, the product can be marketed, which may be called as Phase IV trials, wherein new uses or new populations, long-term effects etc. The approval process of New Drug Applications (NDA) includes sufficient preclinical data for verification of drug's safety and justification of the commencement of clinical trials. The aim behind the formal review is to guarantee the content and format of the submitted materials is in line with the requirements and all the required materials have been submitted. The final consent for conducting trial is given by the approving authority after due advice from the HREC.


The changes includes, establishing definitions for Phase I-IV trials and clear responsibilities for investigators and sponsors[31].
Other issues where the difference appears are, time taken for the approval of a CTA application, time taken in evaluation of marketing authorization application, registration fee, registration process and marketing exclusivity (Table 1).
For the purpose of harmonisation, the International Conference on Harmonisation (ICH) has taken major steps for recommendations in the uniform interpretation and application of technical guidelines and requirements. University (India) and earned his Masters Degree in Pharmaceutics from Punjabi University (India).
This procedure may also be used for generic medicines applications once the data exclusivity periods granted to originator products authorised through this procedure begin to expire. They, in turn, will either approve the assessment or the application will continue into arbitration procedures.
Compliance with Good Manufacturing Practice (GMP)[4] is also required and ensures that the results of clinical trials are unaffected by inadequate safety, quality or efficacy arising from unsatisfactory manufacture.
The competent authority review the application and approve the drug for marketing only if the drug is found to be safe and effective in human being or the drug have more desirable effect as compare to the adverse effect [2].
When a licence is recommended, a European Public Assessment Report (EPAR) is produced and marketing authorisation is issued.
The Drug Administrative Law was further revised in 2001 requiring premarket testing, approval for new drug products, and prohibits drug adulteration[22]. After formal review, the PDAAs send the qualified applications to the SFDA for further review. The commencement of clinical trial takes place only after the due notification to the TGA and the appropriate notification fee to be paid. The therapeutic uses and effective dose ranges are determined in Phase II trials in 10-12 patients at each dose level[32]. This step will ultimately reduce the need to duplicate work carried out during the research and development of new drugs. The new Decentralised Procedure involves Concerned Member States at an earlier stage of the evaluation than under the MRP in an effort to minimise disagreements and to facilitate the application for marketing authorisation in as many markets as possible. This authorisation is valid throughout the European Union and is for five years, however, the extension can be applied to the EMEA three months before the expiration of this period[14]. However, if a medicinal product is supposed to cause potential serious risk to public health, CMS(s) will inform to other CMS, RMS and applicant and further decision in this regard is taken within 30 days. The import drug registration application should be directly submitted to SFDA by the applicant. In CTX scheme, an application to conduct clinical trials is submitted to the TGA for evaluation and comment. In one category (category A) clinical trials can be conducted in other markets with competent and mature regulatory systems whereas the remaining ones fall in to another category (category B) Other than A.
The confirmatory trials (Phase III) are conducted to generate data regarding the efficacy and safety of the drug in ~ 100 patients (in 3-4 centers) to confirm efficacy and safety claims. Therefore, harmonization of drug approval processes either by ICH or WHO may be initiated at global level. Sunil Gupta, he got interested in application of experimental designs for formulation and process development.
The legislation becomes a regulation, rather than a directive, which will ensure key aspects have identical rules throughout the EU.From Test Tubes to AnimalsDrug discovery aims to find potential disease-altering targets, such as a gene or a protein in humans. Within 60 days of the communication of the points of disagreement, all member states reach to an agreement on the action to be taken. SFDA's Department of Drug Registration carefully reviews the completeness of the submitted materials, files the qualified applications and transmits all the materials of qualified applications to the Center for Drug Evaluation (CDE) directly attracted to SFDA.
The clinical trials can be conducted (under the CTX application) without further assessment by the TGA and the conduct of each trial should be notified to the TGA[27,28].
Phase III trials should be conducted on a minimum of 500 patients spread across 10-15 centers, If the new drug substance is not marketed in any other country[32,33,34,35].
He developed novel fourth generation graph invariants and various models for the prediction of biopharmaceutical, pharmacological and physiochemical properties of drugs during his Ph.D. When a candidate compound is found, its safety needs to be tested for a specific indication or disease condition. To evaluate dosage, broad efficacy and additional safety in people (~300) are the main objective of the phase II. After reaching to an agreement of the member states, the RMS records the agreement and informs to the applicant. CDE determine whether the safety and effectiveness information submitted for a new drug are adequate for manufacturing and marketing approval and send the report of review to SFDA.
The clinical trials of category B are under more scrutiny, and approve within 16 to 18 weeks[32].
The new drug registration (using form # 44 along with full pre-clinical and clinical testing information) is applied after the completion of clinical trials.
However, if the member states could not reach an agreement, then CHMP intervenes and take a final decision keeping in view of the written or oral explanations of the applicant[15,16,17,18]. SFDA Carefully consider the recommendations and review results of CDE and makes a decision whether or not the drug registration application can be approved and issues the certificate of drug approval and drug approval number to the qualified applicant. An application is submitted to TGA to register the drug in Australian Register of Therapeutic Goods (ARTG) after the completion of clinical trials. The comprehensive information on the marketing status of the drug in other countries is also required other than the information on safety and efficacy. Candidate compounds need to be introduced into a living biological system (animal) to see if they function as anticipated. These phase III concerns more about safety and effectiveness of drug from data of different populations, dosages and its combination with other drugs in several hundred to about 3,000 peoples[8, 9, 10]. Figure 5 -6 represents the clinical trial approval process and new drug approval process of China, respectively[22,23,24,25]. The application consists of data to support the quality, safety and efficacy of the product for its intended use. The information regarding the prescription, samples and testing protocols, product monograph, labels, and cartons must also be submitted[36].
At least two different species of animals have to be used.From Animals to Human Phase 1 TrialsIf pre-clinical test results support further development, the candidate compound is tested in humans in a phase 1 clinical trial.
A new drug application (NDA) can be filed only when the drug successfully passes all three phases of clinical trials and includes all animal and human data, data analyses, pharmacokinetics of drug and its manufacturing and proposed labelling. The application is assessed (on an administrative level) to make sure for compliance with basic guidelines and further evaluated by different sections and advice can also be sought on key issues to take final decision. The preclinical, clinical reports and risk-benefit analysis (product's beneficial effects outweigh its possible harmful effects) are reviewed at the Center for Drug Evaluation and Research by a team of scientists. This consent may be withdrawn at any time by the participant.Phase 1 trials are conducted in a small number (20 to 80) of healthy volunteers and last approximately one year. Generally approval of an NDA is granted within two years (on an average), however, this process can be completed from two months to several years. A delegate (decision-maker) within the TGA after due advice of the ADEC, take a decision to approve or reject the product.
After the NDA approval, when a company is allowed to distribute and market the product, it is considered to be in Phase IV trials, in which new uses or new populations, long-term effects, etc.
The aim is to find the lowest dose at which the treatment is effective and the highest dose at which it can be taken without causing harm. The innovating company is allowed to market the drug after the approval of an NDA and is considered to be in Phase IV trials. In this phase, new areas, uses or new populations, long-term effects, and how participants respond to different dosages are explored[10, 11].
He has written two monographs in the book entitled " Mathematical Chemistry Monographs, No. When the drug is approved and distributed in the market the drug, it is considered to be in Phase IV trials. Taking around two years, it helps determine the most effective dosages, the best method of delivery (e.g. This is any untoward medical occurrence or effect.The sponsor must inform the Competent Health Authority, within seven or 15 days of receiving the information (depending on the event) and must also record adverse events on an ongoing basis. Annual reports assessing the safety aspects of the clinical trial are required for all trials and assessed by Competent Health Authorities.Transparency requirementsTrials conducted in the EU need to be registered with the EudraCT database. If harm to the trial participant leads to the civil or criminal liability of the investigator or the sponsor, liability is governed by national law. LabWare Linkam Scientific Instruments Limited Molins Technologies Multicore Dynamics Ltd Nanosurf New England Biolabs, Inc.



Effective treatment of neck pain
Holistic treatment for lung cancer in cats jaw
Chinese herbs used in pregnancy


Comments to «Clinical trial authorisation definition»

  1. RadiatedHeart writes:
    Able to formulate treatment plans the development.
  2. itirilmish_sevgi writes:
    Regards to the further benefits of acupuncture have.
  3. sex_ustasi writes:
    May vehemently dislike acupuncture and medicine, Buy Online Herbal Supplements, Herbal.
  4. malakay writes:
    May help women whose migraines passes away and one yr later that woman international Association for.