The Legal Aspects of The Importation and Distribution of Foreign Produced Generic Pharmaceutical Drugs

Introduction

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 Drugs

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:

1. 1. 1. Scheduled Poison (known as Controlled Medicine/Controlled Poison) – Products containing poisons as listed in the First Schedule under Poisons Act 1952; and
      2. 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:

• 1. Preparation for Submission of Application
  2. Screening or Evaluation of Application.
  3. Outcome of Application.
  4. 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.

Regulatory Requirements

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.

TABLE 1

Certificate

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.

TABLE 2

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.

TABLE 3

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

TABLE 4

In respect of Full Evaluation, the PRH needs to provide the information on 2 parts namely¹⁷:

• 1. 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.
  2. 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

Decisions

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

Inspection of GMP and GDP are conducted to ensure the compliance of manufacturers, importers and wholesalers with the current GMP and GDP requirements.²⁰

Licenses

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

TABLE 5

Authors: Nur Izzatie Azlan and Zhilal Adnan

Footnotes

1. 1. 1. 1. 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.
            18. Ibid.
            19. Ibid.
            20. Ibid, page 49.
            21. Regulation 12, CDCR 1984.
            22. Regulation 13, CDCR 1984.