1.1. A significant part of the quality of a finished product is dependent on the quality of the Active Pharmaceutical ingredients (APIs) used for its formulation. Thus, a proper system of qualification of suppliers is necessary to ensure a constant sourcing of APIs of appropriate quality and to safeguard the public health interests. This will be done through standardized quality assessment and inspection procedures.

1.2. The National Pharmaceutical Regulatory Agency (NPRA) under the purview of the Ministry of Health Malaysia has introduced mandatory control of APIs as part of the requirements in the product registration application.

1.3. The implementation began with voluntary submission for New Drug Products in April 2011 and followed by

• Phase 1 - New Drug Products (January 2012)
• Phase 2 - Generic Products containing Scheduled Poison

• New Application (Generic Products containing Scheduled Poison):-
  i. Parenteral Dosage Form : 1 July 2014
  ii. Oral Dosage Form :           1 July 2016
  iii. Others :                              1 July 2018
• Registered Product (*Pharmaceutical products containing Scheduled Poison):- All Dosage Form : Expire on 1 January 2020 onwards
  * API Information must be submitted at least one year before the expiry date.

• Phase 3 - Generic Products NOT containing Scheduled Poison (to be determined)

[Reference: Directives dated 17 March 2011 Bil (12) dlm BPFK/PPP/01/03 Jld 1 and dated 16 January 2014 BPFK/PPP/07/25 (7), Circular dated 27 June 2014 Bil (11) dlm BPFK/PPP/01/03 Jld 3 ]

1.4. The procedure for control of APIs established by the NPRA is based on the following principles:

• A general understanding of the production and quality control activities of the manufacturer;
• Assessment of API data and information, including changes and variations, submitted by the product registration holder (PRH)/ API manufacturer. These data should include the manufacturing process, material specifications and test data and results;
• Assessment of the manufacturing site(s) for consistency in production and quality control of raw materials, with specific emphasis on key raw materials and APIs during and after purification through compliance with Good Manufacturing Practice (GMP);
• Random sampling and testing of APIs (post-marketing surveillance);
• Handling of complaints and recalls; and
• Monitoring of complaints from other agencies and countries.

1.5. The guideline is intended to provide guidance regarding the requirements to be included for APIs in the quality part of the product dossier (Part II-S)

Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical dosage form and that, when used so, becomes an active ingredient of that pharmaceutical dosage form. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the body (WHO Technical Report Series No.970,2012).

3.1. This Guideline encompasses the final APIs of new products for registration and current/exist in registered products. This is applicable to all pharmaceutical products (excluding traditional products, veterinary products, and health supplement products) both locally manufactured and imported.

3.2. Biological active substances and immunological active substances are excluded from the scope of this Guideline. Please refer to relevant guidelines available for Biologics.

3.3. APIs used in products for export only (FEO) are exempted from the requirement for submission of the Drug Master File (DMF) and Certification of Suitability (CEP) in the product application.

3.4. Premixing of API is part of the product manufacturing process; therefore, information on premixed API should be submitted under Part II-P. Submission for Part II-S solely includes information on API only.

3.5. Separate registration of the API is not requirement for the purpose of product registration. However, the required technical documentation pertaining to each API should be submitted with the new product registration application.

3.6. Assessment of an API will be performed once submission of a new product registration application has been done.

3.7. Assessment of an API will also be performed for a registered product prior to a product renewal application (as stated in item 1.3).