Preclinical & Clinical Trial Requirements
The low-down on the situation regarding preclinical & clinical trial requirements in Malaysian pharma. Prepared in association with Skrine, a leading law firm in Malaysia, this is an extract from The Pharma Legal Handbook: Malaysia, available to purchase here for USD 99.
1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?
Malaysia is actively developing its capability in all phases of clinical trials and there is currently no mandatory condition for clinical trials to be conducted locally. However, where drugs are imported into Malaysia for the purpose of clinical trials a Clinical Trial Import License (“CTIL”) is required and where the drug intended to be manufactured in Malaysia solely for producing samples for clinical trials or for registration, a Clinical Trial Exemption (“CTX”) is required.
In addition, as an ASEAN member nation, Malaysia has adopted the ASEAN Guideline for the Conduct of Bioavailability/Bioequivalence Studies. Accordingly, in addition to the CTX, a bioequivalence study (BE) report must be produced for any generic medicine for certain categories of oral immediate release products, including those containing active ingredients which have been previously approved and/or product information which have been previously approved and/or route of administration, strength and dosage form equal to those of products which have been previously approved.
2. How are clinical trials funded?
The Malaysian Ministry of Science, Technology and Innovation (MOSTI) is tasked with providing four (4) research funds including ScienceFund, TechnoFund, InnoFund and Flagship Programme. The TechnoFund is granted for technology developments up to pre-commercialisation stage and the InnoFund is granted for the development or improvement of new or existing products, processes or services with elements of innovation. The Scope of funding for these two initiatives include pre-clinical and clinical testing/trial. In addition, the Clinical Research Malaysia (CRM), a wholly government-owned non-profit organisation under the MOH was established to develop infrastructure for Clinical Research Centre networks and to support global industry sponsored research (ISR) requirements. The CRM is authorised by the Malaysian government to act as a trustee in managing the budgets of clinical trials conducted in the country by receiving and executing its disbursements.
3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?
The single regulatory authority in Malaysia that regulates clinical trials and the licensing scheme for clinical trials is the NPRA. The National Committee for Clinical Research adopted ICH E6 Good Clinical Practice into the Malaysian Guideline for GCP to facilitate the mutual acceptance of clinical data that are intended to be submitted to regulatory authorities. Therefore, all those involved in clinical trials must comply with the international ethical and scientific quality standard and obtain a Good Clinical Practice (“GCP”) certification. The trial should be conducted in accordance with a protocol agreed upon by the sponsor and, if required by the regulatory authority(ies) and which was given approval/favourable opinion by an Institutional Review Board/Independent Ethics Committee (IRB/IEC). The investigator/institution and the sponsor should sign the protocol or an alternative contract to confirm the agreement.
In addition, the investigator/institution is required to fill in and submit a proposal template(s) and a Checklist for Clinical Trial Protocols Involving Human Subjects and Generating Data Intended to be submitted to Regulatory Authorities. Furthermore, before commencing any clinical trial involving product(s) requiring a CTX/CTIL and prior importation/manufacturing product locally for the study, the investigator/sponsor must submit an application for a CTIL/CTX to the NPRA.
Before medical devices are used for the purposes of clinical trials, so long as it is imported into or manufactured in Malaysia it must be registered (or be exempted under the Medical Device (Exemption) Order 2016). The relevant body from which approval must be sought is the MDA. In order to apply for the exemption a notification must be submitted to the MDA who will then issue a No Restriction Letter for the lawful supply of the medical device for any specific use.
4. What are the requirements for consent by participants in clinical trials?
The investigator must obtain and document the informed consent from the subjects of the clinical trials and in its efforts, should adhere to the GCP and ethical principles originally found in the Declaration of Helsinki. Before commencing the trial, the investigator should have the IRB/IEC’s written approval/ favourable opinion of the written informed consent form and any other written information provided to the subjects. Further, any revised written informed consent form, and written information should receive the IRB/IEC’s written approval/favourable opinion in advance of any usage. The subject or the subject’s legally acceptable representative should be informed of new information which may be relevant to the subject’s willingness to continue participating in the trial. The communication of this information should be documented.
The subject or the subject’s legally accepted representative should be informed of all pertinent aspects of the trial and be given ample time and opportunity to inquire about the details of the trial and have all questions answered to his/her satisfaction. The written informed consent form should be signed and personally dated by the subject or by the subject’s legally acceptable representative, and by the person who conducted the informed consent discussion.
5. May participants in clinical trials be compensated?
During the informed consent discussion and when filling in the written informed consent form and any other written information, an explanation on the compensation and/or treatment available to the subject, in the event of a trial related injury, should be included. It is the responsibility of the IRB/IEC to obtain information about the payments and compensation available to subjects.
If required by the applicable regulatory requirement(s), the sponsor should provide insurance or indemnity the investigator/institution against claims aris- ing from the trial save for those arising from malpractice and/or negligence.
The sponsor should obtain from the investigator/institution the following:
– the name and address of the investigator’s/institution’s IRB/IEC
– statement obtained from the IRB/IEC that it is organised and operates according to GCP and the applicable laws and regulations.
– documented IRB/IEC approval/favourable opinion and, if requested by the sponsor, a current copy of the protocol, the written informed consent form(s) and any other written information to be provided to the subjects, the subject recruiting procedures, documents related to payments and compensation available to the subjects, and any other documents that IRB/IEC may have requested.
6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?
If required by the applicable regulatory requirement(s), the sponsor ought to provide insurance or should indemnify (legal and financial coverage) the investigator/the institution against claims arising from the trial except for claims that arise from malpractice and/or negligence. Given that the participants would sign a Clinical Trial Agreement giving their informed consent to participate, unless harm arises as a result of malpractice and/or negligence, participants would have to rely on personal medical insurance in case of other unforeseen events.