The Legal Aspects of the Importation and Distribution of Foreign Produced Generic Pharmaceutical Drugs
To ensure the safety, quality and efficacy of marketed pharmaceuticals products in Malaysia, Drug Control Authority (“DCA”) is responsible for the registration and monitoring of the quality of pharmaceutical products.1
Being one of the DCA Secretariat, National Pharmaceutical Regulatory Agency (“NPRA”) plays a role in implementing regulatory scheme on quality of pharmaceutical products in the market through random sampling and analytical tests. It also administers the licensing scheme for pharmaceutical manufacturers, importers and wholesalers.
Registration is imposed on companies intending to manufacture, sell, supply, import or possess or administer any drugs products, including generic drugs products.2
Generic drug is a drug product that is essentially similar to a currently registered product in Malaysia. The term generic drug does not apply to Biologics.3 It is one of the categories of medicinal products under Control of Drugs and Cosmetics Regulations 1984 (“CDCR 1984”) apart from new drugs product, biologics, natural products and health supplements.
The role of generic drugs is to provide high quality but affordable essential medicines, as it is proven to be cheaper than innovator brands (research-based) brands.4 Generic drugs may be classified into 2 groups5:
a) Scheduled Poison (known as Controlled Medicine/Controlled Poison) – Products containing poisons as listed in the First Schedule under Poisons Act 1952; and
b) Non-scheduled Poison (known as Non-Poison or Over-the-Counter/OTC) – Products containing active ingredients which are not listed in the First Schedule under Poisons Act 1952 and excluding active ingredient which is categorised under health supplements or natural products or cosmetics.
Both categories of generic drugs above require registration with DCA.6
Procedures for Registration of Generic Drugs
Similar to other medicinal products, the procedures for registration of generic drugs generally will be as follows:
a) Preparation for Submission of Application.
b) Screening or Evaluation of Application.
c) Outcome of Application.
d) Inspection & Licensing.
PART A: PREPARATION FOR SUBMISSION OF APPLICATION
Submission of Registration with DCA
Registration with DCA shall be done by the Product Registration Holder (“PRH”), a locally incorporated company, corporate or legal entity, with permanent address and registered with the Companies Commission Malaysia. For foreign company, it needs to appoint a local agent (a company incorporated in Malaysia) to be the PRH. The appointed PRH would then be responsible for all matters pertaining to the registration of the products.7
Registration is made via an online platform, Quest. A first-time PRH applicant shall first apply for Quest membership and purchase USB Token for submission of registration.
Prior to the submission, the PRH should make sure it complies with the regulatory requirements for generic drugs, including the following:
(a) Bioequivalence (“BE”) Requirements
The purpose of establishing BE is to demonstrate equivalence in biopharmaceutics quality between the generic medicinal product and a comparator medicinal product. This is to allow bridging of preclinical tests and clinical trials associated with the comparator medicinal product.8 During submission of registration, PRH of generic drugs shall submit a complete BE report with all the appendices and comparative dissolution profile data/report according to the relevant guidelines. The complete BE report should consist of BE study protocol, clinical study report, method validation report, bioanalytical report and pharmacokinetic and statistical report.9
(b) Other Requirements & Conditions (Labelling, Packing, Educational Materials)
Apart from the above, the PRH and the foreign company (as the case may be) shall be aware of the other requirements, restrictions and conditions, as per Table 1.
|Product Names Not Permitted to Be Registered||Examples of non-permissible product names are:
> Use of superlatives (kuasa – power, sihat – healthy, sembuh – heal, syurga – paradise)
> 20 disease names as stated in the Medicines (Advertisement and Sale) Act 1956 (e.g., diabetes, asthma, cancer)
> Use of offensive or indecent names (Xenxual to symbolize sensual)
> Use of product names similar to existing approved product names
|Further details are provided in Appendix 17 of the Drug Registration Guidance Document Third Edition, issued January 2022 (“DRGD 2022”).|
|List of Permitted, Prohibited and Restricted Substances||The PRH shall be aware of the following substances:
> List of Prohibited Active Ingredients and its Combinations (such as Astemizole, and combination of Ampicillin + Cloxacillin, respectively)
> List of Restricted Active Ingredients and its Combinations (such as Acetic Acid in Expectorant)
> List of Prohibited and Restricted Excipients (such as Amaranth and Tartrazine, respectively)
> List of Permitted and Restricted Colouring Agents (such as Calcium Carbonate and Guanine, respectively)
|Further details are provided in Appendix 18 of DRGD 2022.|
|General Labelling Requirements||The labelling shall include important information at respective positions such as at the packaging outer carton, immediate labels, or blister/strips.
The information includes the product name, dosage form, name of active substance(s), strength of active substance(s), batch number, manufacturing date etc.
|Further details are provided in Appendix 19 of DRGD 2022|
|Specific Labelling Requirements||There are specific labelling requirements on all 207 specific substances, such as abiraterone, ace inhibitors, benzoyl peroxide, ginseng, methyl salicylate, opioid, paracetamol, tramadol, vitamin K etc.||Further details are provided in Appendix 20 of DRGD 2022.|
|Special Conditions for Registration of a Particular Product or Group of Products||Special conditions are imposed on the registration of all 9 particular product or group of products, such as blood products, midazolam, paracetamol in combination with caffeine, vaccines (including COVID-19 vaccines) etc.||Further details are provided in Appendix 21, DRGD 2022.|
|Educational Materials||For risk minimisation measures, the PRH shall provide educational materials to healthcare professionals and patients in reducing risk(s) for a particular product.
This applies to products containing active ingredient such as, sodium valproate and retinoids.
|Further details are provided in Appendix 22 of DRGD 2022.|
Compliance with Good Manufacturing Practice (“GMP”) and Good Distribution Practice (“GDP”) are prerequisites for application for product registration.10 The PRH shall ensure the following:
a) Good Manufacturing Practice (GMP)
GMP is imposed on foreign companies that manufacture medicinal products outside Malaysia.11 Those foreign manufacturers are subjected to GMP conformity assessments through acceptable GMP evidences. The valid GMP evidences differ according to the location of pharmaceutical manufacturer, as per Table 2.
Location of Pharmaceutical Manufacturers
Valid GMP Evidence in Malaysia
|Pharmaceutical manufacturer located on a site within jurisdiction of a Pharmaceutical Inspection Co-operation Scheme (“PIC/S”) Participating Authority.||GMP evidence issued by its local National Drug Regulatory Agency (“NDRA”)|
|Pharmaceutical manufacturer located in an ASEAN member country.||GMP evidence issued by its local NDRA is accepted if the NDRA is included as a Listed Inspection Service under the ASEAN Sectoral Mutual Recognition Arrangement (“MRA”) for GMP Inspection of Manufacturers on Medicinal Products.|
|Pharmaceutical manufacturer not located on a site within jurisdiction of a PIC/S Participating Authority.||GMP evidence issued either by any PIC/S Participating Authority, or any NDRA that has a cooperation agreement such as MRA with PIC/S.|
The absence of any valid GMP evidence as above would require the foreign companies to apply for Foreign GMP Inspection by NPRA, which shall be made by a Malaysian registered company acting on its behalf.
b) Good Distribution Practice (GDP)
GDP is required to ensure that foreign companies adopt proper distribution and store management procedures according to GDP, in relation to the premise, facilities, stock handling and control, disposal of materials or products, vehicles and transportation of products.12
PART B: SCREENING OR EVALUATION OF APPLICATION
After the online submission of product registration application via Quest, the application shall undergo an initial evaluation (screening process), to ensure the submitted application is complete with the required data/information.
Payment & Hard Copy Documents
Only a complete application shall be accepted and approved for payment. Upon screening approval, the applicant is requested to proceed with: (a) payment as in table below; and (b) submission of hard copy documents (if applicable). For generic drugs, all documents can be submitted online, unless the files size are too large which require hard copy submission.13
The applicable fee for registration of generic drugs, are as per Table 314.
> Generic (Scheduled Poison)
> Generic (Non-scheduled Poison)
|RM1,000.00||Single Active Ingredient: RM1,200.00||RM2,200.00|
|Two/ more Active Ingredient: RM2,000.00||RM3,000.00|
Upon confirmation of payment, the application with the submitted data shall be evaluated. Review of applications shall follow a queue system.
Evaluation for Product Registration
For registration of generic drugs, 2 methods of evaluations are applicable, namely Full Evaluation and Abridge Evaluation, which are as per Table 4.15
|Product Category||Full Evaluation||Abridge Evaluation|
|Generics (Scheduled Poison)||Applicable
[Evaluation Timeline: 210 working days]16
|Generics (Non-Scheduled Poison) (or known as OTC)||Applicable to all products of this category, unless stated in Abridge Evaluation.
[Evaluation Timeline: 210 working days]
|Generics (non-scheduled poison) that are evaluated under abridged evaluation include, but are not limited, to the following:
> Antiseptics/skin disinfectants:
> Locally acting lozenges/pastilles
> Topical analgesic/counterirritants.
> Topical nasal decongestants
> Emollient/demulcent/skin protectants.
> Oral care.
> Medicated plasters/patch/pad
> Topical antibacterial
[Evaluation Timeline: 116 -136 working days]
In respect of Full Evaluation, the PRH needs to provide the information on 2 parts namely17:
a) Part I – Administrative data and product information such as Product Particulars, Product Formula, Particulars of Packing, Label (Mock-up) For Immediate Container, Outer Carton, Proposed Package Insert, Consumer Medication Information Leaflet (RiMUP), and Supplementary Documentation.
b) Part II – Data to support product quality (Quality Document) (such as Drug Product (Finished Product), Quality Overall Summary, and Drug Substance)
Meanwhile, for Abridge Evaluation, the PRH needs to provide information on product such as Product Particulars, Product Formula, Particulars of Packing, Label (Mock-up) For Immediate Container, Outer Carton, Proposed Package Insert, Consumer Medication Information Leaflet (RiMUP), Particulars of Product Owner, Manufacturer, Importer and Other Manufacturer(s) Involved and Store address.
PART C: OUTCOME OF APPLICATION
An application may be approved or rejected by DCA, and the decision shall be sent via email/official letter to the PRH.
DCA has the power to at any time reject, as well as cancel or suspend the registration of any product if there are deficiencies in safety, quality or efficacy of the product or failure to comply with conditions of registration. Re-submission of product registration for a rejected application due to safety and efficacy reasons shall not be accepted within 2 years after the rejection.18
Product Registration Number
For successful registration, the PRH shall be notified by DCA and a product registration number (i.e. MAL number) shall be assigned to the registered product via QUEST system. The registration number is specific for the product registered with the name, identity, composition, characteristics, origin (manufacturer) and PRH, as specified in the registration documents.19 The applicant shall refer to the product registration approval notification sent by DCA or the Approved Product Registration List in the NPRA website.
The registration status of a product shall be valid for 5 years or such period as specified in DCA database (unless the registration is suspended or cancelled by DCA).
PART D: INSPECTION & LICENSING
Inspection of GMP and GDP are conducted to ensure the compliance of manufacturers, importers and wholesalers with the current GMP and GDP requirements.20
Once the product is registered, the applicant should apply for the applicable licenses as required in CDCR 1984 in the respective prescribed forms to NPRA.21 The applicable licenses, its prescribed forms and the processing fees can be summarised as per Table 5.22
Type of Licenses
Prescribed Form in CDCR 1984
|Manufacturer’s License (PRH that manufactures the registered products in the premises specified in the licence and sells by wholesale or supplies the products)||
|Wholesaler’s License (PRH that sells by wholesale or supplies the registered products from the address of the business premises specified in the licence)||
|Clinical Trial Import License (PRH that imports any product for purposes of clinical trials, notwithstanding that the product is not a registered product)||
|Import License (PRH that imports and sells by wholesale or supplies the registered products from the address of the premises specified in the licence)||
1. https://www.npra.gov.my/index.php/en/about /drug-control-authority-dca/about-the-dca.
2. Regulation 7, CDCR 1984
3. https://www.npra.gov .my/index.php/en/prescription-main-page.html.
4. National Pharmacy Call Center, What Prescribers Should Know About Generic Medicines, First Edition, 2013, pg.2.
5. https://www.npra.gov.my/index.php/en/ prescription-main-page.html.
6. https://www.npra.gov.my/index.php/en/component/content/article/37-english/faq/623 -product-registration.html?Itemid=1391.
8. Drug Registration Guidance Document (DRGD) Third Edition, Second Revision January 2022, Appendix 16.
10. Drug Registration Guidance Document (DRGD) Third Edition, Second Revision January 2022, page 49.
11. National Pharmaceutical Regulatory Agency Foreign GMP Inspection Guidance Document, 8th Edition (September 2021) retrieved from https://www.npra.gov.my/easyarticles/images/users/1133/Guidance-Document-Foreign-GMP-Inspection- _Sep-2021_8th-Ed.pdf.
12. Good Distribution Practice 2nd Edition 2013 retrieved from https://www.npra.gov.my/images/Guidelines_Central/Guidelines_on_Regulatory/Good%20Distribution%20Practice%202nd%20 Edition%202013.pdf.
13. Drug Registration Guidance Document (DRGD) Third Edition, Second Revision January 2022, page 40.
14. Ibid, Appendix 9.
15. Ibid, Appendix 14.
16. Ibid, Appendix 5.
17. Ibid, Appendix 15.
20. Ibid, page 49.
21. Regulation 12, CDCR 1984.
22. Regulation 13, CDCR 1984.