Version 20APR2006 rev 10 Dec 2010

Transcription

1 Official Local Language: Thai The conduct of clinical trials in is regulated by Ministerial Regulation No. 14, B.E (A.D. 1989) (Thai only) Link to legislation: (follow Laws & Regulations under the Information Columns, Thai & English versions available) Link to published guidance documents: Regulatory Agency (Thai, English version available) (medical devices guidelines, English) Regulatory Agency RA Name: Drug Control Division of the Food and Drug Administration (FDA) of the Ministry of Public Health (MOPH) Regulatory approval/authorisation of the study is not required. However, submission to the RA to obtain an import licence is required if the investigational products have to be imported into (details in Importation section). If the investigational products are supplied locally, submission to the RA to obtain an Import License is not required. Documentation requirements vary for different types of products, trials and where products are manufactured. Importation An import licence is required and may be requested from the RA following approval of a study by the appropriate EC(s). The import license is study specific and can be applied per site or for all sites at a time depending on the availability of EC approval letters. Importation may be made in several shipments using one import licence. The application form NorYorMor1 (NYM1) must be submitted to the International Affairs and Investigational New Drug Section of the RA to request authorisation to import investigational products; JorPorMor (JPM) must be submitted to the Medical Devices Division to request authorisation to import medical devices for research. Relevant documents should be attached to the forms; each application form has its own checklist for the submission. The application forms must be completed in Thai; supporting documents are accepted in Thai or English. Two A4 ring-bound hard copies of the application package are required for license application of the study drugs and one hard copy of the application package is required for license application of medical devices. The application forms are available in hard copy from the RA directly or can be downloaded from the RA website at (NYM1, Thai only) and (JPM3, Thai only). Page 1 of 10

2 Documents are submitted to the One Stop Service Center, where applications and relevant documents will be checked for completeness and sent to the appropriate departments for review. Import licences will then be issued or requests for amendment or clarification will be provided to the applicant by phone or fax. Responses to requests for clarification should be received within 3 working days. The entire process takes approximately 4 weeks for study drugs and 1 week for medical devices. The import licence lists the name of the importer (site/institution or sponsor), the protocol, the name and amount of investigational product/medical device authorised for import. There is no timeframe following the issue of the licence in which the study must start, and notification of study start is not required. For the study drug, the import license has no expiry date. The amount of drug stated on the Import License must be an amount to be used in one year. For a study with treatment duration more than one year, multiple licenses are required. The medical devices import license, on the other hand, does have an expiry date (in most cases, the expiry date stated on the license is the expiry date of EC approval), therefore, a renewal of the license may be required if the study duration is more one year. The amount of medical devices stated on the Import License must be an amount to be used throughout the study. To import medicinal products and medical devices, the applicant must hold an importer authorisation ; governmental organisations (i.e. hospitals) or pharmaceutical companies (sponsor) or a sponsor s representative may hold an importer authorisation licence. A non-licenced representative may provide assistance with the completion of the application and compilation of the submission, however the licence and the responsibility are in the name of the authorised importer. Address for submission of all applications: One Stop Service Center Food and Drug Administration Ministry of Public Health 88/24 Tiwanond Road, Nonthaburi Tel: Int (medicinal products) Int (medical devices) Address of International Affairs and Investigational New Drug Section: International Affairs and Investigational New Drug Section Drug Control Division Food and Drug Administration Ministry of Public Health 88/24 Tiwanond Road, Nonthaburi Tel: Int or Int Fax: Int Page 2 of 10

3 Guidelines on Drug Importation for Clinical Research is available at this link: Fees: There are no fees for application of study drug import license. The application fees for medical devices import license (including lab kit) is THB100 per application. Link to the regulation: (Thai only) The licence and Certificate of Analysis for the shipped drug/device must be submitted to Customs by the licenced importer for clearance of goods. Labeling and GMP requirements The following statements should be included on the labels: Name/code of investigational product protocol identification, e.g. protocol number and/or protocol name content and size (i.e. number of tablets per bottle, number of bottles per carton) strength of active ingredient (for blinded trials active ingredient or placebo may be indicated) lot/batch number Sponsor name and address expiry date or retest date storage conditions statement for clinical trial use only in Thai Language required: Thai. If the drug is to be administered solely by site staff, labels in English are accepted; however, the term For clinical trial use only must be in Thai. Thai is still the preferred label language. Link to local GMP requirements: (Thai, English), (site is temporarily off-line) then go to GMP. Ethics Committee Link to accredited EC (temporarily offline): (Thai only) Local EC approval is required and must be issued before an application for the import licence can be made. If the study is conducted exclusively at any of the following 8 sites with an accredited EC, approval is needed only from the local ethics committee of each of the sites: Siriraj, Mahidol University Ramathibodi, Mahidol University King Chulalongkorn Memorial, Chulalongkorn University Maharai Nakorn Chiang Mai, Chiang Mai University Srinagarind, Khon Kaen University Songklanagarind, Prince of Songkhla University Phramongkutklao The for Tropical Diseases, Mahidol University Page 3 of 10

4 For studies at hospitals affiliated with the MOPH, approval from the Ethic Committees of MOPH is required. MOPH has two Ethic Committees that can review and approve the studies, one committee is under Department of Medical Services (Ethical Review Committee for Research in Human Subjects, Ministry of Public Health) and another committee is under Department of Medical Sciences (Ethics Committee of Institute for the Development of Human Research Protections or called IHRP ). One application may be made to cover all MOPH sites, however the local ethics committees for these participating sites still require approval of the study if the participating sites have IRB/IEC. For participating sites with no IRB/IEC, notification that the study is being conducted at the site is required. Notification is made by the site PI to institutional director and/or his/her supervisor; depending on the local requirement, a letter usually suffices. The institutional director and/or the supervisor will provide acknowledgement of receipt of this notification. Apart from local ECs and MOPH EC, the applicants may submit the protocol for approval to a newly established Joint Research Ethic Committee (JREC). The JREC is a private committee and while it has additional applicable charges, it is able to approve submissions with 1-2 months after submission, compared to the 2-3 months of the Local EC and the 3-4 months for the MOPH EC after submission. Over 20 local ECs including 7 of the sites listed above are members of JREC. Siriraj is not a member of JREC. The submission to JREC is optional but researchers can submit the protocol to JREC only if their local ECs are members of JREC. The investigator can still submit to their local EC as usual. If the investigator prefers to submit to JREC, then two approval letters will be issued, one from JREC and one from the local EC. For the approval process JREC will communicate with local EC in one process. For some local ECs, once JREC approves, they will provide the approval upon receipt of a notification from JREC that the study is approved; but for some local ECs, even though JREC has approved, the local ECs still have to review but it will be an expedited review. Link to JREC s Website outlining its member: (Thai and English) In general, ethics committees meet once every month, but some may meet twice a month. The approval letter generally indicates the PI name, study title, study site and the approved documents with version numbers. There is no time frame following approval in which the study must start and notification of study start is not required; expiration of approval is committee specific. Documentation requirements vary for different types of products, trials and where products are manufactured. A complete list of the documentation requirements in English for the MOPH EC is linked below. Document requirements for other ECs are committee-specific and should be checked in advance. Page 4 of 10

5 The EC application form for each individual committee should be generally completed in Thai; the supporting documents are generally accepted in Thai or English, however some ECs may have their own requirements for some documents (for example, the study proposal in Thai). All information given to or used by patients must also be in Thai. Hard copy submission only is required and the number of copies depends on the individual EC. If any of the 8 sites listed above with accredited ECs are involved in the study together with MOPH sites, and if any of these EC approvals are available at the time of MOPH EC application, these approvals should be included in the MOPH submission package. If shipment of blood samples out of the country is a requirement of the protocol, certain ECs (the MOPH EC, for example) require a Material Transfer Agreement (MTA) that must be signed by the hospital (in most cases, PI and faculty) and the recipient (in most cases, recipient scientist and head of recipient scientist at central laboratory). Two witnesses are required for MOPH MTA. The MOPH MTA form is found in the MOPH guidelines. The MTA template of other local ECs can be found in their websites. Some ECs also require a copy of the signed Clinical Trial Agreement between the site and sponsor, although this may be submitted following EC approval or when the agreement is available. The EC approval may expire after a set period of either one or two years; however, not all ECs define expiration of approval. Progress reports should be submitted to the EC annually in all cases for renewal of approval/acknowledgement of receipt. The EC will renew the approval, if appropriate, or may require clarification or additional information before making a decision. The applicant is the Principal Investigator of each site and is responsible for both submission and further communication with the EC. One of the Principal Investigators from the participating sites is selected by the PIs of all participating sites to make the single submission to the MOPH EC. Link to documents and forms: Instructions for submission of a study protocol and relevant documents as well as guidelines for the preparation of a research proposal are provided by the ECs and can be found as follows: MOPH: Ethical Review Committee for Research in Human Subjects, Ministry of Public Health Ethics Committee of Institute for the Development of Human Research Protections Instructions for submission of a research study: (Thai) Instructions for submission of a research study MOPH English (Thai) Instructions for submission of a research study (Thai) Page 5 of 10

6 (IHRP) King Chulalongkorn Memorial Srinagarind Siriraj Instructions and guidelines are not provided in writing but the forms to be used for submission can be found at the following link (Thai, English) following link (Thai) Instructions for submission of a research study (Thai, English) Ramathibodi Maharaj Nakorn Chiang Mai Phramongkutklao Songkhlanagarind The for Tropical Diseases JREC following link (Thai) following link (Thai, English) following link (Thai only) following link (Thai only) following link (Thai and English) Instructions, guidelines, approval timelines and forms are provided online at the following link (Thai and English) Addresses and contact details for Thai ECs Initial Submission Fees: THB 10,000 approx Chulalongkorn University EC THB Ramathibodi EC THB Siriraj EC THB Srinagarind THB Maharaj Nakorn Chiang Mai THB 5000 for Tropical Diseases THB 5000 IHRP (Sor Kor Mor) THB JREC THB (plus submission fee required by each local EC for initial submission) Some ECs do not charge a submission fee. Page 6 of 10

7 Most ECs also charge overhead fees for projects sponsored by commercial companies (about 20 % of the total budget, in average). The formula for calculation of overhead costs is committee-specific. Informed Consent Informed consent must comply with ICH GCP guidelines and the guidelines of the respective ECs which are provided either as a booklet and/or on the specific EC website. Language required: Thai. English is also often requested; if the subject is from a minority group who cannot read the Thai language, translation to the subject s own language is required, and the translation must be approved by the appropriate EC. Advertisement Advertising for clinical trials is permitted and approval from the appropriate EC is required. Data Protection Data protection should comply with the Official Information Act, B.E (Thai) Insurance and Indemnity There are no standard requirements or guidelines for insurance. ECs, however, may require insurance and any type of insurance would be acceptable. ECs require a statement in the informed consent that treatment is available for study-related injury. A statement confirming whether or not compensation is also available should be included; either scenario is acceptable to the EC. The requirement for indemnity varies between institutes and should be individually checked. Amendments There is no country-specific distinction between Major and Administrative amendments, the ECs follow ICH-GCP guidelines. In general, addition of extra sites, extra procedures for patients, extra tests on stored samples or additional information to be collected should be submitted for approval prior to implementation, unless required for the immediate safety of patients. Changes to the investigator brochure, investigator CV and administrative changes to the protocol require acknowledgement of receipt by the EC only. All protocol amendments and the addition of extra sites must be submitted to appropriate EC by the applicant for review and approval or acknowledgement of receipt, as appropriate, before implementation. The amendment application form required depends on the individual EC. Committee-specific forms for amendment submission may be found in the appropriate EC guidelines or on the respective website. Page 7 of 10

8 Amendments submitted to the EC must highlight the changes to the document, i.e. old text and new text. After obtaining the Import License from Thai FDA, any amendments/changes to the followings must be submitted to Thai FDA for approval before implementation: Changes to the study medications or any changes that involves the quality or the safety of study medications Protocol Amendments or any changes that involve or may affect safety of the subjects If any changes to the study medication or the protocol amendments has the purpose related to subjects safety that require immediate action, then they can be immediately implemented; and submission to Thai FDA has to be done within 15 days from the day of implementation The following amendments/changes must be notified to Thai FDA for acknowledgement: Protocol Amendments that do not have any affects to the safety of subjects Early termination of the study from other reasons rather than the subjects safety reasons Amendment to the Investigator Brochure Changes to the study medications that do not involves the quality or the safety of study medications In case of early termination or early completion of the study, must notify Thai FDA within 30 days from the day of termination/completion The manual detailing requirements and instructions for submission of the amendments can be found at: (Thai only). Amendment Submission Fees: EC: Some ECs request for the submission fees of the amendments. Fees can be found on each EC specific website. If submission is via JREC, significant protocol amendment submission will be charged at THB plus THB1000 for each local EC (this is the fee to pay JREC for approval of protocol amendment and also to the local EC, a member of JREC. RA: There are no fees for application of study drug import license due to the amendments. The application fees for medical devices import license due to the amendments (including lab kit) is THB100 per application. Safety Reports ECs require both foreign expedited safety reports (serious, suspected and unexpected) received from sponsors and serious adverse events occurring at the particular site. The investigator making the study approval submission should submit safety reports and events to the appropriate EC and sponsor. All safety updates and periodic reports must also be submitted. SAE reporting forms are determined by the individual EC. Safety reporting should be performed in a timely manner as defined by the individual EC. Guidelines on timelines are not provided by all ECs, but some ECs require reporting of Page 8 of 10

9 local SAEs within 5 working days following occurrence. Some EC require reporting of both global and local SAEs/AEs. Following review of safety reports, the EC may require revision of informed consent documents to include updated safety information; revised informed consent documents must be approved by the EC prior to use. It is the responsibility of the Importer to submit Safety Reports to Thai FDA. The FDA Drug Control Division indicates in the import license that SAEs reports must be submitted to the FDA Drug Control Division, in compliance with ICH E2A guidelines. The official Thai FDA regulations and guidelines regarding SAE reporting requirements can be found at Submission of SAEs to FDA Drug Control Division applies to local serious unexpected adverse drug reactions exclusively. However, the importer may submit Safety Reports that occurred in other countries to Thai FDA at least annually in form of Annual Safety Reports/Line Listing. There is no preferred reporting format; any format is acceptable. Reporting should be hand delivery. Electronic reporting is not accepted. There are no specific unblinding requirements. PVG contact point, address, fax and telephone numbers in the RA and EC are as detailed in the appropriate sections. Progress and Annual Reports Individual ECs should receive regular progress reports at least annually. An EC may require a line-listing of local adverse events attached to the progress reports. Specifications of progress report and forms can be found in the EC-specific guidelines. For some ECs, progress and annual reports are related to issuing yearly renewal of study approval. The RA does not require an annual report. Annual Submission Fees: EC: Some ECs request for the submission fees of annual submission. Fees can be found on each EC specific website. End of Trial Notification The appropriate ECs require notification of early termination and study completion; there are no specific timelines for this report. Reporting forms depend on the individual EC, but it is normally in the form of a letter. The initial applicant would normally make this notification, but if the trial was stopped by the sponsor, the sponsor is responsible for notifying the ECs. The RA requires notification from the initial applicant of the end of study or early termination within one month of completion. Details of destruction or return of remaining study drug are also required within 1 month of occurrence (requirement for reporting of device destruction is not documented). There is no official definition of the end of trial, but it is usually interpreted as last visit of last patient. Clinical Trial Report Page 9 of 10

10 Not all ECs require submission of Clinial Trial Report, A final study report should be submitted to all involved ECs as per their individual requirements by the initial applicant. MOPH EC requires submission of Clinical Trial Report within 6 months after study completion. The RA does not currently require a clinical trial report. Page 10 of 10