DRGD 12th Revision (July 2026): What Changed for Drug Manufacturers

Scope: the July 2026 revision and effective dates

The DRGD is NPRA's main guidance for registering medicines, health supplements and natural products in Malaysia. NPRA amends it month by month and publishes a consolidated revision twice a year. Directive No. 18 of 2026, dated 10 July 2026, requires all applicants and product registration holders to use the 3rd Edition, 12th Revision, July 2026 for regulatory matters related to product registration, effective 31 July 2026. It replaces the 11th Revision of January 2026.

NPRA's list of updates for this revision contains 24 amendments made between February and July 2026. That is a formal count: several are contents-page entries or the same reference added in three places, and a few concern only health supplements and natural products. Many of the underlying requirements took effect earlier, through their own directives and circulars, so the revision date is not the date every change applies.

Source: NPRA List of Updates for DRGD 3rd Edition, 12th Revision July 2026; the directives and circulars listed under Sources.

The previous revision (11th, January 2026) had already brought in the reliance and priority-review routes for additional indications, the Farmatag® security label supplier directive of 7 October 2025 and a set of safety statements, including for GLP-1 receptor agonists. NPRA publishes a separate list of updates for each revision.

DEG/EG testing for oral liquid products

Diethylene glycol (DEG) and ethylene glycol (EG) contamination of solvent excipients caused more than 300 child deaths from contaminated cough syrups in several countries in 2022-2023, according to the directive. Directive No. 8 of 2026 sets Malaysia's control, and the 12th Revision adds the list of high-risk ingredients to DRGD Appendix 18.

• Scope. Registered oral liquid products that contain high-risk active ingredients or excipients, in every product category - scheduled poisons (A), non-scheduled poisons (X), health supplements (N) and natural products (T). NPRA's FAQ confirms it applies only to oral solutions, and only to those containing high-risk ingredients.
• High-risk ingredients. Glycerin, propylene glycol, polyethylene glycol, sorbitol and sorbitol solution, maltitol and maltitol solution, hydrogenated starch hydrolysate, and other sugar polyols synthesised via catalytic hydrogenation. The list is not exhaustive: if the holder or manufacturer knows of another high-risk ingredient in the formula, it should be tested too.
• Limit and method. Not more than 0.1% (1,000 ppm) for each of DEG and EG, by gas chromatography (GC-FID or GC-MS). TLC can be used for screening, but GC confirmation is still required.
• What to test. Either the high-risk ingredient or the finished product - not both. Whichever is chosen, every lot of the ingredient or every batch of the finished product must be tested. Testing only at the development stage is not enough.
• Where. In the manufacturer's own laboratory or a private laboratory with validated DEG/EG methods; NPRA recognition of the laboratory is not required.
• Imported products. The Malaysian registration holder is responsible for making sure the foreign manufacturer carries out the testing.

Source: NPRA Directive No. 8/2026 and its FAQ (12 February 2026).

DEG/EG testing is not part of the finished-product specification in dossier section P5.1; the documents are submitted separately. The consequences of a failure reach beyond one batch: affected batches are recalled, and so are other batches and other products made with the same suspect raw-material lot. A product that does not comply after 1 April 2027 has its registration status reviewed. NPRA also tests high-risk products through risk-based and market sampling.

Animal-derived materials: evidence and label declarations

A circular of 16 March 2026, following the Drug Control Authority's meeting of 5 March 2026, changes both the evidence NPRA asks for and the label rule. It is reflected in DRGD Appendix 4 (biologics) and Appendix 19 (general labelling), and it replaces NPRA's circulars of 24 May 2023 and 13 August 2024 on the same subject.

• DNA testing is no longer mandatory to confirm the absence of animal-derived materials used in manufacturing the active substance. A validated analytical test, including a DNA PCR test on the final product, remains one option; NPRA also accepts a manufacturer's declaration based on the manufacturing process, a satisfactory explanation of the purification process, or relevant process-validation or development data. Acceptability is product-specific and decided by the assessor.
• Primary packaging is out of scope. The source of primary packaging materials is no longer assessed or declared, in line with WHO, EMA and US FDA practice.
• Components of the final product must be declared. If an animal-derived material is part of the final product - active substance, excipient, preservative, gelatin or capsule shell - the specific animal source must be stated clearly on the label. A negative DNA or analytical result does not remove this requirement.
• Optional supplementary statement. If DNA testing of the final product finds no animal DNA, the outer carton may add a statement such as "PORCINE ORIGIN. No traces of porcine DNA found in the final product."

In the DRGD labelling table, item 17 changed from "to declare source of ingredients derived from animal origin, unless a satisfactory confirmation can be provided verifying the absence of animal materials in the final product" to "to declare source of all ingredients derived from animal origin, including active substances, excipients, and gelatin" - on the outer carton and the immediate label. The rule applies immediately to new applications and to products under evaluation. For a European manufacturer, the practical point is gelatin: hard and soft capsules, and gelatin-based excipients, now need the species on the Malaysian label regardless of test results.

Additional indications: updated reliance requirements

DRGD section 20.4 covers new or additional indications (AI) for registered innovator products. Since the January 2026 update (11th Revision), each AI category has a standard and a reliance version:

• AI Full Evaluation - the indication is approved by at least one of NPRA's reference agencies: EMA, UK MHRA, Swedish Medical Products Agency, ANSM France, US FDA, TGA Australia, Health Canada, PMDA Japan or Swissmedic.
• AI Verification - approved by at least two of them; an EMA centralised approval counts as one.
• Reliance versions of both let NPRA rely on the reference agency's assessment report. The indication must have been approved by the chosen primary reference agency within the last three years, and the indication, dosing, patient population and directions for use must be similar to that agency's approval.

The June 2026 update adds one condition: if the chosen reference agency did not approve the most stringent indication, dosing regimen, patient group or directions for use among those approved by the reference agencies, the applicant must provide a clinical justification at submission. In practice, compare the EMA, FDA and other reference approvals before choosing the agency to rely on. The AI reliance checklist has moved out of the DRGD into the NCE and biologics application forms on NPRA's website. Reliance for initial registration is a separate route - see Malaysia's fast-track routes.

Product-specific safety statements and supply restrictions

These changes matter only if your portfolio contains the substance. Safety statements in DRGD Appendix 20 must appear in the package insert (PI) and, where stated, the Consumer Medication Information Leaflet (RiMUP).

Source: NPRA List of Updates for DRGD 12th Revision (April, March and June 2026 updates) and the directives cited there.

Keeping labels and package inserts in line with these directives is a registration holder duty. See pharmacovigilance obligations of the MAH and variations and renewals after registration.

E-labelling and other changes

• E-labelling. Under the 2023 e-labelling directive, the voluntary period runs from 1 May 2023 to 31 December 2026, and OTC generics were added on 1 August 2025. Holders using e-labelling had to inform healthcare providers with printed Dear Healthcare Provider (DHCP) letters and printed copies of the PI or RiMUP. A circular of 12 May 2026 stops these printed letters and copies with immediate effect; healthcare providers use the QR code on the pack. The 12th Revision adds this circular to sections 7.10 and 7.11 and Appendix 19. It is not a general abolition of paper package inserts.
• Who can be a registration holder. Section 5.1 no longer bars government agency and university names in the holder's name. Government agencies and research or higher education institutions may act as holders or manufacturers through subsidiary companies - directly only with strong justification such as national interest or emergencies - and private companies may not use names that resemble them.
• Health supplements and natural products. Health supplement fees now have their own table: RM 2,200 / 3,000 for general and functional claims and RM 4,000 / 5,000 for disease risk reduction claims (one / two or more active ingredients). New functional claims were added for L-carnitine, vitamin B2 and zinc, and the natural-product labelling table was revised. Fees for medicines did not change - see the registration fee and timeline table.
• Editorial. In Appendix 3, "radionucleotide" was corrected to "radionuclide" in the definition of a new radiopharmaceutical substance.

Review checklist for manufacturers and the MAH

NPRA addresses its directives to registration holders, so in Malaysia these are obligations of the holder - the Marketing Authorisation Holder (MAH), called Product Registration Holder (PRH) by NPRA - who must get the data and labels from the manufacturer.

1. Reference the 12th Revision in every submission prepared after 31 July 2026, and check dossiers drafted against earlier revisions.
2. Oral solutions: list products with glycerin, propylene glycol, PEG, sorbitol, maltitol or other polyols; decide whether to test each excipient lot or each finished batch; confirm a GC method and laboratory; plan the COA (and POA for full evaluation) for applications received after 1 April 2027.
3. Animal-derived components: identify every animal-derived ingredient in the final product, including gelatin capsules, and put the species on the outer carton and immediate label. For animal materials used only in manufacturing, choose the evidence - DNA test, process declaration or purification data.
4. Additional indications: before filing a reliance application, compare the approvals of all reference agencies and prepare a clinical justification if the agency you rely on did not approve the most stringent conditions.
5. Portfolio check: compare your products with the substance table above and update the PI and RiMUP where needed.
6. Track monthly updates. NPRA changes the DRGD every month between revisions; the next consolidated revision is expected in January 2027 under the twice-yearly pattern.

Frequently asked questions

What is the latest DRGD revision in Malaysia?

The Drug Registration Guidance Document, 3rd Edition, 12th Revision, July 2026. Directive No. 18 of 2026 requires all applicants and registration holders to use it from 31 July 2026. It replaces the 11th Revision of January 2026.

What changed in DRGD 12th Revision for medicines?

DEG/EG testing for oral solutions with high-risk excipients, a mandatory animal-source declaration on the label for animal-derived components, a clinical justification for some reliance applications for additional indications, new safety statements for lamotrigine, sunitinib, itraconazole, vancomycin, caffeine citrate and vitamin B6, supply restrictions for oral oxycodone and ascorbic acid injection, and the end of printed DHCP letters for e-labelled products. Medicine registration fees did not change.

When does DEG/EG testing become mandatory in Malaysia?

On 1 April 2027. Directive No. 8 of 2026 took effect voluntarily on 1 April 2026 with a one-year transition. New applications received after 1 April 2027 must include DEG/EG results in the Certificate of Analysis, and registered products must have test records ready for inspection.

Does a negative DNA test remove the need to declare gelatin on the label?

No. Since NPRA's circular of 16 March 2026, any animal-derived material in the final product, including gelatin, must have its animal source declared on the label. A negative DNA result on the final product only allows an additional statement on the outer carton, such as "PORCINE ORIGIN. No traces of porcine DNA found in the final product."

Do registered products need a variation for DEG/EG testing?

No. NPRA's FAQ states that only new applications must submit the COA and POA; for registered products the documents must be available during GMP/GDP inspections and NPRA's quality monitoring programme.

You might also find useful

• Drug Registration in Malaysia: Process, Timeline and Requirements (2026)
• After the MAL Number: Renewals, Variations and the Holder's Obligations in Malaysia

• Sources:
• NPRA - Drug Registration Guidance Document (DRGD), 3rd Edition, 12th Revision, July 2026 (main body): npra.gov.my (PDF)
• NPRA - List of Updates for DRGD 3rd Edition, 12th Revision, July 2026 (February-July 2026): npra.gov.my (PDF)
• NPRA - Directive No. 18 of 2026: use of DRGD 3rd Edition, 12th Revision July 2026 (10 July 2026): npra.gov.my (PDF)
• NPRA - Directive No. 8 of 2026: DEG and EG testing of active ingredients, excipients and/or finished products in oral liquid dosage forms (10 February 2026): npra.gov.my (PDF)
• NPRA - FAQ on DEG and EG testing requirements (English version): npra.gov.my (PDF)
• NPRA - Circular on analytical testing and label declaration for products containing animal-derived materials (16 March 2026): npra.gov.my (PDF)
• NPRA - Circular on stopping printed DHCP letters and printed PI/RiMUP copies under e-labelling (12 May 2026): npra.gov.my (PDF)
• NPRA - DRGD e-book page (current revision, appendices and lists of updates): npra.gov.my
• Editorial note: This page is general business and regulatory information for manufacturers evaluating Malaysia. It is not legal or regulatory advice. NPRA amends the DRGD monthly; check the current revision, directives and circulars before acting. Last reviewed: 2 November 2026.