Summary results from the Country Report are presented here relating to 1—Organization of the authority; 2—Good Review Practices: Elements of Good Review Practices in place at NPRA and Quality Decision-Making Practices used to make regulatory decisions. This is followed by description of types of review models/registration pathways, the review process, key milestones in the review process, and metrics measuring the performance for approvals in 2019.

Country Report

Organization of NPRA: NPRA is an authority that operates within the administrative structure of the Health Ministry and regulates medicinal products for human use and for veterinary use. NPRA is funded entirely by the government and currently employs approximately 500 staff members, including 101 reviewers dedicated to evaluating applications for marketing authorizations or product licenses for medicines. Of these reviewers, 33 specialize in assessing new chemical entities and biologics. The professional background of these reviewers was primarily pharmacy. NPRA’s scope of activities includes marketing authorizations/product licenses; clinical trial authorization; post-marketing surveillance; laboratory analysis of samples and site inspections/visits, GMP inspections, and the licensing of premises.

Elements of Good Review Practices (GRevP), which are key to building quality into the regulatory process, are summarized in Table 1. The agency has identified three key measures for introducing quality initiatives: improving efficiency, ensuring consistency, and enhancing stakeholder satisfaction. GRevP have been applied by the agency in the review practice, through guidelines, internal standard operating procedures (for reviewers and advisory committee members) along with evaluation templates and checklists. NPRA’s internal quality policy, ISO 9001:2015 certified since July 2017, and its dedicated quality department reflect its commitment to international standards and delivering quality products and services. In addition, the Country Report identified other quality measures instigated by NPRA, including transparency and communication, emphasizing the agency's high priority on maintaining openness and transparency in its relationships with the public, professionals, and industry. Examples of this include providing details of technical staff to contact, official guidelines to assist applicants, as well as providing the ability to track the progress of applications. The agency identified three key incentives for allocating resources to activities that enhance regulatory system transparency: ensuring safety measures; improving staff morale and performance, and strengthening confidence in the system.

The agency also supports continuous improvement through external and internal audits, review of both assessor and applicant feedback, and utilization of an internal tracking system to monitor consistency, timeliness, efficiency, and accuracy of the review. The agency conducts on-the-job training and provides internal and external training programmes for assessors, which are sometimes undertaken in collaboration with other agencies. Several training programmes include examinations and successfully completing these courses are mandatory for professional advancement. Agency staff also have opportunities to attend international conferences and may receive the Ministry of Health’s support for pursuing a postgraduate degree. The agency had not implemented placements or secondments to other regulatory authorities as a training method for assessors.

Table 1 Quality in the review process

Quality decision-making practices: NPRA has a formally defined and codified framework in place that forms the basis of the decision to approve or reject a Marketing Authorization Application (MAA). Key measures implemented by NPRA include having a structured approach; assigning clear roles and responsibilities (decision makers, advisors, information providers); evaluating both internal and external influences or biases; examining alternative solutions; and considering uncertainty. NPRA also re-evaluate as new information becomes available for an MAA, ensure transparency of the process, provision of a record trail, and effectively communicate the basis of the decision.

The registration pathways in Malaysia: Like other NRAs, NPRA has introduced alternative registration pathways to expedite approvals and improve patient access. Fig. 1 illustrates the alternative registration pathways, including their criteria and timelines. Apart from standard pathway, NPRA also allows certain promising new medicines, including vaccines, to reach patients with unmet medical needs earlier (via the conditional registration pathway) while ensuring measures are in place to manage the risks inherent in additional data still being required [7]. NPRA has adopted the principle of reliance through Facilitated Registration Pathways (FRPs), enabling an expedited registration process by relying on reference agencies’ assessment reports for products seeking approval in Malaysia. Other abbreviated pathways with shorter timelines are Orphan Medicines, Conditional Registration of Pharmaceutical Products During Disaster, and Priority Review; for which pre-defined criteria must first be met. The majority of NASs approved in 2019 went through the standard approval pathway.

Fig. 1

Review process: The review process is described in Fig. 2 (steps A to H) and key aspects of the marketing authorization process are summarized in Table 2. Upon submission of an ASEAN Common Technical Dossier (ACTD) via the online system, the dossier is validated to ensure completeness. The application is accepted if all essential documents are provided, and scientific regulatory review ensues to evaluate the product's quality, efficacy, and safety. External inputs are sought from appointed experts or clinical specialists in the relevant field for NASs and biosimilars. After initial review, the assessor corresponds with the applicant, providing a list of questions to request further information or documents. Once the additional data is deemed satisfactory, the final evaluation report is presented at NPRA’s product evaluation committee meeting, followed by presentation to the Drug Control Authority (DCA) for final marketing authorization decision.

Fig. 2

The review process at NPRA. WD Working Days, CD Approximate Calendar Days

Table 2 Key characteristics of NPRA marketing authorization processMetrics Results

Twenty-four NASs were approved by NPRA in 2019, of which 10 (42%) were new chemical entities and 14 (58%) were biologics (including 1 vaccine). The included products were also categorized based on their assessment route: Path I (priority review), Path II (standard review), or Path III (Facilitated Registration Pathway). Of products approved in 2019, 1 (4%) was assigned to Path I, while 3 (12%) were designated Path III (Table 3).

Table 3 Characteristics of 24 NAS approved by NPRA in 2019

The therapeutic areas of the products approved vary, with anti-cancer, immunomodulatory, and anti-diabetic products representing a combined proportion of 50%.

Overall Approval Times

The median time for overall approval, from the date application received (Step A) to approval granted (Step H) (see Fig. 2), including both applicant and agency time, for the 24 NAS was 399 calendar days. The inter quartile range (IQR) was 275 to 472 days (25th to 75th percentile). NPRA’s review timelines for new chemical entities and biologics are 245 working days (~362 calendar days) for standard review and 120 working days (~177 calendar days) for priority review (Fig. 1). However, these targets are for agency time only, rather than overall approval time.

Breakdown of Time Spent in the Approval Process

The approval process is divided into three key stages: (i) time from receipt of the dossier to the start of scientific assessment; (ii) scientific assessment time; and (iii) authorization time. The median time for all stages is shown in Fig. 3. Comparing the three main stages of NPRA approval process for medicines approved in 2019, the agency spends most of its time in scientific assessment compared to the other two stages. The median time for scientific assessment, which includes both agency and applicant time, was 294 calendar days with an IQR range of 209 to 421 calendar days (25th to 75th percentile). Meanwhile, the median time from dossier receipt to the start of scientific assessment, was 62 calendar days (an IQR of 35 to 88 calendar days), whereas the median time for the authorization stage, from scientific assessment completion to marketing authorization, was 7 calendar days, matching the median for the year 2017 (Fig. 3).

Fig. 3

The three main components of the approval process for 24 NAS approved by NPRA in the year 2019 compared to 2017; n number of applications

Comparing the results for the year 2019 to those for 2017 (Fig. 3) for the same milestones showed an overall reduction in approval time (399 vs 515 calendar days) as well as the time from receipt of the dossier to the start of scientific assessment (135 vs 62 calendar days). However, the median scientific assessment time increased slightly by 15 calendar days (294 vs 279 calendar days).

Time from Dossier Receipt to Start of Scientific Assessment

The two components of this stage are: (i) validation time (from submission made to agency’s acceptance of the file), and (ii) queue time (from agency acceptance to the start of scientific assessment). The overall median of the two components in 2019 was 20 calendar days (IQR of 8 to 25 calendar days) and 42 calendar days (IQR of 13 to 71 calendar days) for validation time and queue time respectively (Fig. 4). When compared to the year 2017, overall improvement was observed in validation time and queue time. The reduction in time for the year 2019 was most notable for biologics. While new chemical entities also showed reductions in the validation time and the queue time, the decreases were less substantial (Fig. 4).

Fig. 4

Time from dossier receipt to start of scientific assessment for the years 2019 and 2017 by product type, validation (submission to agency to acceptance to file) and queue time (acceptance to file to start of primary assessment); n number of applications

Scientific Assessment Including Agency and Applicant Time

Overall scientific assessment time was observed to have increased slightly for the year 2019 compared to 2017 (Fig. 3). A breakdown by product type revealed that median scientific assessment time (which includes agency and applicant time) for biologics increased by 19 calendar days (IQR: 2019, 204–319 calendar days; 2017, 212–255 calendar days), while the median scientific assessment time for new chemical entities decreased by 44 calendar days (IQR: 2019, 295–434 calendar days; 2017, 305–641 calendar days).

Meanwhile, median agency time in 2019 vs 2017 increased for both biologics (165 vs 116 calendar days) and new chemical entities (234 vs 211 calendar days), respectively. Reduction in applicant time was noted for both biologics (95 vs 101 calendar days) and new chemical entities (179 vs 229 calendar days) respectively. For new chemical entities, a drop in IQR from 360 calendar days in 2017 to 110 calendar days in 2019 was also noted.

Agency scientific assessment time was broken down further into primary scientific assessment, the time taken for the agency to review the dossier prior to sending out the first set of questions and the subsequent time for applicant’s responses. This process may be repeated, resulting in several review cycles. The median primary scientific assessment time for the 24 NASs approved in 2019 was 81 calendar days (Fig. 5), equivalent to approximately 42% of total agency scientific assessment. Compared to the year 2017, this had increased by 31 calendar days. In 2017, the median primary scientific assessment time of 50 calendar days represented approximately 29% of the total agency scientific assessment time [4].

Fig. 5

Agency and applicant scientific assessment time for 24 NASs approved by NPRA in 2019. n number of applications

Median total applicant time to respond to questions was 108 calendar days for the NASs approved in 2019. This compares with a median of 131 calendar days for total applicant time in 2017 [4]. Applicants took a median of 44 calendar days to respond to questions raised by the agency following the primary scientific assessment (41% of total applicant time). In 2017 this was 41 calendar days (29% of total applicant response time). For this cohort of 24 NASs, completion of scientific assessment took 3 cycles for 1 NAS (4.2%), 4 cycles for 7 NASs (29.2%), and 5 cycles for the remaining 16 NASs (66.7%). In 2017, 2 cycles were taken for 1 NAS (3.8%), 3 cycles for 3 NASs (11.5%), 4 cycles for 9 NASs (34.6%), 5 cycles for 8 NASs (30.8%), and 6 cycles for 5 NASs (19.2%) [4].