Bioequivalence Requirements for Generic Medicines in Malaysia

When NPRA requires bioequivalence

NPRA's requirements sit in Appendix 16 of the Drug Registration Guidance Document (DRGD, 12th revision, July 2026), read together with the ASEAN Guideline for the Conduct of Bioequivalence Studies. A generic has the same qualitative and quantitative composition in active substances and the same dosage form as the comparator; different salts, esters or isomers count as the same substance unless they differ significantly in safety or efficacy. The BE requirement has been introduced in stages and currently covers generic products containing scheduled poisons in these forms:

Source: NPRA DRGD Appendix 16 (July 2026); NPRA FAQ on BE desktop evaluation (2023).

BE data is required both for a new generic registration and for registration renewal. Dosage forms outside this scope do not currently need BE data, and NPRA reviews the scope from time to time.

The comparator: Malaysia Comparator Product

• Use the MCP. The reference product must be the innovator or comparator registered with the Drug Control Authority in Malaysia. NPRA publishes the Malaysia Comparator Product list by dosage form and updates it regularly.
• Prove where the reference came from. The dossier includes the reference product's outer carton showing batch number, manufacturer address and expiry date, plus its product leaflet.
• A reference bought elsewhere - made at a different site from the MCP, or without the manufacturer's address on the carton - is accepted only if it is qualitatively identical to the MCP (minor differences such as colouring aside), its dissolution profile is similar to the MCP's, and the substance does not have a narrow therapeutic index.
• Innovator never registered in Malaysia? If the innovator has never been registered in Malaysia, NPRA classifies the application as a hybrid, not an ordinary generic.
• MCP no longer available or not on the list? NPRA asks applicants to contact its BE unit at be_sug@npra.gov.my before planning the study.

Where the study can be done

Since 1 January 2012, BE studies used for Malaysian registration must be run at clinical and bioanalytical facilities listed in NPRA's BE Centre Compliance Programme, during their valid listing period. Clinical and bioanalytical sites are listed separately and can be combined, as long as each phase falls inside that site's listing period.

Source: NPRA foreign and local BE centre pages; country count by RHMI from the centre entries shown on 25 October 2026. Listing periods differ by site - check each clinical and bioanalytical site against your study dates.

Studies from anywhere else are not automatically rejected. Three routes apply:

• ASEAN BE Centre List. Since 18 February 2025, studies run at centres on the ASEAN BE Centre List during their listing period are exempt from BEDE for eligible generics - immediate-release oral solid dosage forms with systemic action containing scheduled poisons. The July 2026 Appendix 16 states that the link to that list will be provided once it is established.
• Facilitated Registration Pathway. Products eligible for the FRP are also exempt from BEDE. How the FRP works.
• BEDE - Evaluation on the Need for BE Study Inspection. For generics and certain hybrid products, a study from an unlisted centre in any country, or run outside a centre's listing period, goes through this desktop evaluation. It relies on inspection reports issued by other regulators for both the clinical and bioanalytical sites - from within five years before or after the study, product-specific ones carrying more weight. Without such reports the application is rejected at screening, and GCP or GLP certificates alone do not replace them; the 2023 BEDE FAQ points applicants to a study-specific inspection instead. The outcome is acceptance for registration review or a study-specific inspection that must end satisfactorily.

BEDE is not a biowaiver and not a centre listing: a favourable BEDE decision only means the study can go to registration review without a study-specific inspection - it does not establish bioequivalence or put the centre on NPRA's list. Whatever the route, NPRA can still inspect a study site if concerns arise during review; refusing an inspection, or an unsatisfactory one, leads to rejection of the product. In 2024 NPRA carried out 23 BE centre inspections, 22 of them abroad.

The test product: same site, same process

• The biobatch must match the product you register: same manufacturing site, same process, same drug substance and formula.
• Batch size of at least 100,000 units or one tenth of production scale, whichever is greater, unless justified.

Reusing an existing study

An existing study from India, China or Europe has to pass four separate checks: the comparator, the status of both study sites on the study dates, the study design, and whether the tested product is the product you will register. Clearing the centre's status does not clear a comparator or manufacturing mismatch. NPRA's BE FAQ sets out what can bridge the gaps - each case "can be considered", with the decision made after full evaluation of the dossier:

• Biobatch made at a different finished-product site: comparisons of formula, specifications and process; batch analyses of at least three pilot batches; comparative dissolution on at least three batches from each site, including the biobatch; an assessment report from a DCA reference-country agency; and a valid GMP certificate for the biobatch site, which must be listed in the CPP.
• Different API manufacturer: a separate package on the API - properties that affect bioavailability such as polymorphism and particle size, specifications, impurities and manufacturing - with batch analyses of at least one batch each and comparative dissolution.
• Larger biobatch than the batch size you register: a reference-agency assessment report and comparative dissolution data.
• Unlisted European site: confirm early that regulator-issued inspection reports for both sites can be shared with NPRA - confidentiality restrictions do not remove the BEDE requirement.

Study design and dissolution

• Immediate release: fasting conditions, unless the comparator's product information says it is taken only with food - then fed. Products with specific formulation characteristics, such as microemulsions or solid dispersions, may need both fasting and fed studies.
• Modified release: single-dose studies under both fasting and fed conditions; NPRA can ask for a multiple-dose study.
• Acceptance: the ASEAN guideline's standard single-dose criterion - a 90% confidence interval within 80.00-125.00% for the test/reference geometric mean ratios of AUC and Cmax. Narrow-therapeutic-index and highly variable products can have different criteria.
• Comparative dissolution profiles accompany the BE report: at least 12 units per product, in pH 1.2, 4.5 and 6.8 buffers plus the QC release medium where applicable, sampling at least every 15 minutes, with similarity shown by a suitable statistical method such as the f2 factor. Surfactants should be avoided, and a claim that the API is insoluble in every medium is not accepted on its own.

Biowaivers: when an in vivo study is not needed

• Additional strengths. BE at one or two strengths can cover the others if they share the process and qualitative composition, are quantitatively proportional (with defined tolerances for low-dose products), and comparative dissolution confirms it.
• BCS-based - Class I only. NPRA currently accepts only Class I (high solubility, high permeability) biowaivers, product-specific and per strength, for immediate-release oral solids. Narrow-therapeutic-index drugs, buccal or sublingual products and different esters or isomers are excluded.
• Second source. For an immediate-release oral solid generic, a second manufacturing source may use comparative dissolution against the registered first source instead of a new study - only if NPRA has evaluated the first source's BE study and found it satisfactory, formulation, equipment, raw materials, process, environment and specifications are identical, and process validation on three batches is satisfactory. It does not cover a new first-source registration.
• Comparator no longer available. NPRA lists 54 active substances and combinations that may be considered for a biowaiver because the comparator - registered before 1999 - is no longer available in Malaysia. All of NPRA's criteria must be met, and process validation and comparative dissolution data on three consecutive batches replace the BE report. Fludrocortisone acetate, phenobarbitone and dapsone are on this list; all three also appear on NPRA's 2025 list of medicines most requested under special approval.
• Product-specific decisions. NPRA's working committee has waived BE for, among others, single-ingredient cholecalciferol above 1,000 IU, nystatin, sevelamer carbonate (with binding studies) and generic radiopharmaceuticals.

What goes into the dossier

The complete BE report - study protocol, clinical study report, method validation report, bioanalytical report and pharmacokinetic and statistical report - goes into QUEST3+ under section P9, Product Interchangeability/Equivalence Evidence, together with the comparative dissolution data, following NPRA's BE submission checklist. NPRA can ask for a hard copy. Biowaiver requests use their own checklists. The application is filed by the Malaysian Marketing Authorisation Holder (MAH).

A practical sequence for a foreign manufacturer

1. Classify the product. Generic or hybrid - check whether the innovator has ever been registered in Malaysia, and ask NPRA for product classification if unclear.
2. Check the waiver lists first. The 54 unavailable-comparator substances, BCS Class I, additional strengths, second source.
3. Lock the comparator. Find the MCP for your dosage form; if you already have a study against another reference, prepare the identity and dissolution evidence.
4. Check your existing study's centre. Listed by NPRA during the study dates? On the ASEAN BE Centre List? If not, plan for BEDE - or for a study-specific inspection.
5. Match the biobatch and API source to the registered product, or prepare NPRA's bridging data for each difference.
6. Assemble P9 with the MAH that will file and hold the registration.

Frequently asked questions

Which generic medicines need a bioequivalence study in Malaysia?

Generic products containing scheduled poisons in oral solid dosage forms with systemic action: immediate-release forms, modified-release forms, and effervescent, dispersible, orodispersible, sublingual, buccal and chewable forms. BE data is required for new generic registrations and for renewals. Dosage forms outside this scope do not currently need BE data.

Which reference product must the BE study use?

The innovator or comparator product registered with the Drug Control Authority in Malaysia - in practice the Malaysia Comparator Product (MCP) on NPRA's list. A reference bought from another site must be shown to be identical to the MCP. If the innovator has never been registered in Malaysia, the application is treated as a hybrid.

Can a BE study done in India be used for registration in Malaysia?

Yes, if the clinical and bioanalytical sites are listed in NPRA's BE Centre Compliance Programme during their valid listing period - 27 of the 42 foreign centres listed as of 28 September 2026 are in India. Studies from unlisted sites, or done outside the listing period, go through NPRA's BEDE desktop evaluation first.

Are there NPRA-listed BE centres in China?

No Chinese centre appears on NPRA's foreign BE centre list as of 28 September 2026. A study run in China therefore goes through the BEDE desktop evaluation, unless the centre is on the ASEAN BE Centre List or the product qualifies for the Facilitated Registration Pathway.

When can a generic avoid an in vivo BE study in Malaysia?

Through a biowaiver: for additional strengths that meet proportionality and dissolution conditions, for BCS Class I products only, for a second-source product made identically to an approved first source, or for the 54 substances and combinations NPRA lists where the comparator is no longer available, if all criteria are met - with process validation and comparative dissolution data on three batches instead.

Where does the BE report go in the Malaysian dossier?

The complete BE report - protocol, clinical study report, method validation, bioanalytical report and pharmacokinetic and statistical report - goes into QUEST3+ under section P9, Product Interchangeability/Equivalence Evidence, together with the comparative dissolution data. The Marketing Authorisation Holder files it.

You might also find useful

• Registering Chinese and Indian Pharmaceuticals in Malaysia
• NPRA UKK List 2025 Malaysia: 50 Medicines in English

• Sources:
• NPRA - DRGD Appendix 16: Bioequivalence (BE) Requirements, 3rd edition, 12th revision, July 2026: npra.gov.my (PDF)
• NPRA - Malaysia Comparator Product (MCP) for BE Study: npra.gov.my
• NPRA - Foreign Bioequivalence Centres and Local Bioequivalence Centres: npra.gov.my
• NPRA - Biowaiver considerations based on unavailability of comparator product and other considerations: npra.gov.my
• NPRA - FAQs: Bioequivalence: npra.gov.my
• NPRA - FAQs: Desktop Evaluation on the Need of BE Study Specific Inspection (BEDE), 2023: npra.gov.my (PDF)
• NPRA - Malaysian Guideline for Bioequivalence Inspection, 2nd edition, October 2024: npra.gov.my (PDF)
• ASEAN Guideline for the Conduct of Bioequivalence Studies: asean.org (PDF)
• Editorial note: This page is general business and regulatory information for manufacturers evaluating Malaysia. It is not legal or regulatory advice. Centre lists, comparator lists and biowaiver lists change; check NPRA's current pages and directives before planning a study or a submission. Last reviewed: 25 October 2026.