Biologics have emerged as a significant treatment for various diseases in Malaysia. With their increasing relevance in addressing chronic diseases and demand for personalized medicine, understanding the registration process for these complex products is crucial. Here, we delve into the intricate steps and requirements mandated by the National Pharmaceutical Regulatory Agency (NPRA) for biologics registration in Malaysia.
Registration of Biologics in Malaysia
Biologics hold a pivotal place in treating conditions like cancer, autoimmune disorders, and infectious diseases. The NPRA meticulously oversees the registration of biologics, adhering to the ASEAN Common Technical Dossier (ACTD) format.
Step-by-Step Overview of the Registration Process
Pre-submission of Application (Preparation): Before the formal application, submitting a pre-submission application to the NPRA is crucial. This includes a concise overview of the biologic, its proposed indication(s), and the clinical development plan. The NPRA reviews this submission and offers guidance.
Submission: Upon NPRA's pre-submission approval, the applicant proceeds with the full registration application. This comprehensive application follows the ACTD format, encompassing administrative, quality, safety, and clinical data.
Regulatory Outcome: The NPRA meticulously evaluates the registration application, deciding on approval or rejection. Additional information or clarifications might be requested. If approved, the NPRA issues a marketing authorization for the product, specifying approved indications and relevant details.
Post-Registration Process: Once registered, continuous submission of pharmacovigilance data to the NPRA is mandatory. This data is vital for monitoring the product's safety and efficacy post-marketing.
Key Requirements for Biologics Registration
Manufacturing Standards: Strict adherence to Good Manufacturing Practice (GMP) is paramount.
Data Submission: Comprehensive quality, non-clinical safety, and clinical data must be provided.
Pharmacovigilance Plan: An effective plan to monitor post-market safety is required.
Details of Submission Requirements
Pre-submission of Application: The application must include details about the biologic, its mechanism of action, proposed clinical trials, manufacturing process, and preclinical safety studies.
Submission: The ACTD format is mandatory, encompassing administrative, quality, safety, clinical studies, risk management, and pharmacovigilance plans.
Expedited Registration of Biologics in Malaysia
The applicants can seek for expedited approvals for Biologics from NPRA, Malaysia. There are possible pathways for expedited registration. The applicant may choose the pathways that best fits for their situation –
Facilitated registration pathway
Conditional Registration of Biologics
Facilitated registration pathway for biologics, including biosimilars
The applicant may opt for the facilitated registration pathway for the biologics under abbreviated and verification reviews.
Abbreviated Review: Limited independent assessment based on prior approval by one reference agency.
Verification Review: NPRA ensures product conformity to registration conditions approved by two reference agencies. The agency submitting the qualifying supporting documents for Verification Review is referred as Primary Reference Drug Regulatory Agency
This pathway involves specific eligibility criteria, required documents, and timelines:
Submission within two years of approval by the primary reference drug regulatory agency.
Compliance with manufacturing facility inspections by PIC/S members.
Consistency in all aspects of the product's quality with the chosen reference agency's approval.
Requirement for Declaration Letters for DMF, intended use, and indication.
Exclusions for products needing stringent assessments or having rejected/warning status by regulatory agencies.
Compliance with the chosen reference agency's approved package insert and stringent dosing regimens.
Conditions for vaccines may vary according to local practices.
Formal request and letter of intent submitted to NPRA.
Complete Common Technical Document (CTD) data requirements and stability study following ASEAN guidelines.
Assessment reports, post-approval variations (if applicable), and documents from the primary reference agency.
Proof of approval from the primary reference agency.
Declaration letter from the product owner/PRH addressing various aspects of product quality and intended use.
Timeline for Registration Process:
The NPRA approval timelines for biologics under Verification Review and Abbreviated Review are 90 and 120 working days respectively. The NPRA correspondence is limited to three times within 60 working days and NPRA may change the evaluation timeline if deadlines are not met.
Conditional Registration of Biologics
The conditional registration of Biologics allows promising Biologics to reach patients with unmet medical needs earlier. This pathway manages risks by requiring additional data. NPRA ensures a structured approach for early access to medicines while maintaining stringent evaluation criteria and continuous monitoring to ensure patient safety and efficacy.
Scope and Eligibility for Conditional Registration:
Conditional registration applies to new chemical entities and biologics based on early Phase II clinical data.
Requirements include comprehensive quality and non-clinical safety data as per the Drug Registration Guidance Document.
Requesting Conditional Registration:
The product registration holder (PRH) must formally request conditional registration, justifying the product's alignment with conditional registration criteria.
Justifications include serious debilitating or life-threatening diseases, emergency use, or orphan medicine designations.
Criteria for Conditional Registration Fulfillment:
Positive risk-benefit balance backed by scientific evidence.
Commitment to provide comprehensive data post-registration.
Addressing unmet medical needs and public health benefits.
Assessment of Conditional Registration by NPRA:
NPRA evaluates requests thoroughly; non-compliance with requirements may lead to rejection.
If approved, specific conditions are stipulated, including confirmatory trials, risk management plans, and periodic reporting.
Renewal and Full Registration:
Conditional registration lasts two years, renewable up to two times with possible extensions.
NPRA reviews renewal applications based on risk-benefit balance, requiring interim reports and supporting documents.
Cancellation and Authority Rights:
DCA may cancel conditional registration if trials fail to verify predicted benefits or if evidence demonstrates product inefficacy or safety concerns.
DCA reserves the right to exercise discretion beyond guideline requirements.
Navigating the Biologics Registration Maze
The registration of biologics in Malaysia demands precision and adherence to stringent NPRA requirements. Early engagement with NPRA during the development phase is recommended, as their guidance proves invaluable. Following these outlined steps and meeting the essential criteria is pivotal for a successful registration process.
Are you looking for expert guidance and support in navigating the biologics registration process in Malaysia? Contact Artixio today! Our team of regulatory experts can provide tailored assistance to streamline your registration journey and ensure compliance with NPRA standards.