FAQs for NDP

1)    What is NDP?

Answer:

New Drug Products (NDP) is defined as any pharmaceutical products that have not been previously registered in accordance with the provisions of the CDCR 1984.

An NDP may be classified according to the following categories:

(a)    New NCE (single/ combination products with an active substance never registered by DCA)

Defined as an active moiety/ radiopharmaceutical substance that has not been registered in any pharmaceutical product.

An active moiety is defined as the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds) or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance.

A radiopharmaceutical substance is defined as a radionucleotide, ligand or the coupling mechanism to link the molecule and the radionucleotide that has not been registered in any pharmaceutical product.

(b)    Hybrid NCE (single/ combination products with registered active moieties)

All other products registrable at New Drug Section which do not fall under (a).

Examples of Hybrid NCE (combination) products:

i.              Combination of registered chemical entities

ii.             Combination of registered chemical entity(s) in new chemical form(s)

iii.            Combination of registered chemical entity(s) in new chemical form(s) and registered chemical entity(s)

Examples of Hybrid NCE (single) products:

i.              Registered chemical entity in a new chemical form

ii.             Registered chemical entity in a new dosage form

iii.            Registered chemical entity in a new dosage strength with a change in dosing/ posology

iv.           Registered chemical entity for use by a new route of administration

v.             Registered chemical entity for new indication(s), dosage recommendation(s) and/or patient population(s)

vi.           A generic product for which its innovator has never been registered by DCA

Flowchart to determine NDP classification, registration requirement and evaluation timeline:

2)    Is there any other pathway for product registration other than the normal pathway?

Answer: Yes.

                      i.        Full Evaluation (Conditional Registration)

·         Applies to new registration applications for New Drug Products and Biologics

·         At the point of submission, the product must be registered in at least one Drug Control Authority (DCA) reference agencies

·         A conditional registration does not apply to additional indications submitted post-registration

·         Once a product has been granted a full registration that is not subjected to any specific conditions, the full registration approval cannot be reverted into a conditional registration approval. However, the approval of additional indication with less than comprehensive clinical data may be considered on case-to-case basis

·         A conditional registration is valid for two years. Thereafter, the conditional registration may be renewed 2 times (with the possibility of 2 extensions of 2 years each)

·         Please refer to the Guidelines On Conditional Registration For New Chemical Entities And Biologics for further details

Directive No. 15 Year 2018. Ref. BPFK/PPP/07/25 (15) Jld 2 : Direktif Untuk Melaksanakan Guidelines On Conditional Registration For New Chemical Entities And Biologics

                    ii.        Full Evaluation via Abbreviated and Verification Review

·         Applies to New Drug Products and Biologics including biosimilars

·         Abbreviated Review applies to a product that has been evaluated and approved by one (1) reference drug regulatory agency

·         Verification Review applies to a product that has been evaluated and approved by two (2) reference drug regulatory agencies

·         For details, please refer to Guidelines on facilitated registration pathway: abbreviated and verification review. The guideline provides information on the eligibility criteria, procedures and requirements for submitting application to register a product via abbreviated or verification review. The implementation of the guideline was on 1 April 2019.

Directive No. 7 Year 2019. Ref. BPFK/PPP/07/25 (7) Jld 3: Direktif Untuk Melaksanakan Guidelines On Facilitated Registration Pathway: Abbreviated And Verification Review

                   iii.        Abrdiged Evaluation

3)    What are the related guidance documents for registration of NDP in Malaysia?

Answer:

                      i.        Drug Registration Guidance Document (DRGD)

                     ii.        International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use

                    iii.        Malaysian Pharmacovigilance Guidelines

                   iv.        The ASEAN Common Technical Dossier (ACTD) for the Registration of Pharmaceuticals for Human Use

                     v.        The ASEAN Common Technical Requirements (ACTR)

-       ASEAN Guideline on Stability Study of Drug Product

-       ASEAN Guideline on Submission of Manufacturing Process Validation Data for Drug Registration

-       ASEAN Guidelines for Validation of Analytical Procedures

-       ASEAN Guidelines for the Conduct of Bioavailability and Bioequivalence Studies

-       ASEAN Variation Guideline for Pharmaceutical Prodcuts

Please also refer to this link for the guidelines available on the NPRA website:

https://www.npra.gov.my/index.php/en/nce-guidelines.html[FD1] 

4)    Is the Risk Management Plan (RMP) required for a New Drug Application?

Answer: Yes it is a requirement. Kindley refer to the Malaysia Pharmacovigilance Guidelines (2016 edition) for information on RMP.

P5.5 SITUATIONS WHEN A RISK MANAGEMENT PLAN SHOULD BE SUBMITTED

P5.5.1 RMP for New Drug Products/Biologics

                 i.       An RMP or an update, as applicable, may need to be submitted at any time during a product’s life-cycle.

                ii.      RMP or an update will normally be expected, with an application involving a significant change to an existing registered product:

·         New dosage form;

·         New route of administration;

·         New manufacturing process of a biotechnologically-derived product;

·         Paediatric indication;

·         Other significant change in indication

               iii.      A significant change in indication is a change of approved indication(s) of a product where the new treatment target population differs materially from the one for which the product was previously approved. This includes (but is not limited to):

·         A new disease area, a new age group (e.g. paediatric indication),

·         A move from severe disease to a less severely affected population,

·         2nd line or other therapy,

·         At the request of the Authority when there is a concern about a risk affecting the benefit-risk balance,

·         At the time of the renewal of the product registration if the product has an existing risk management plan. An updated RMP should always be submitted if there is a significant change to the benefit-risk balance of one or more medicinal products included in the RMP.

5)    What are the requirements for hybrid products?

Answer: The requirements include dossier for:

·         Part I (CD and hardcopy)

·         Part II (CD and hardcopy)

·         and Part IV (CD only)

*The non-clinical overview (Part III – CD only) may be provided as supporting documents.

*9 sets of proposed package inserts and published clinical papers/ in-house synopses for the pivotal clinical studies may need to be provided on a case-to-case basis.

6)    Would NPRA require local clinical studies upon registration process for NDP/NCE?

Answer: No. The clinical studies need not necessarily be done locally.

7)    For product applications with bioequivalence studies, what is/ are the reference product(s)/ comparator(s) needed to conduct the studies?

Answer: Kindly refer to the NPRA website        Industry        Generic Medicines

      Bioequivalence        Generic Product List for BE studies       Refer to the related list (download).

Kindly refer to this link to refer to the reference product(s)/ comparator(s):

https://www.npra.gov.my/index.php/en/generic-product-list-for-be-studies

8)    What are the guidelines to refer to, for clinical development studies for combination products application?

Answer: These guidelines may be referred to:

                   i.       EMA Guideline on clinical development of fixed combination  medicinal products.

http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2017/03/WC500224836.pdf

                  ii.      US FDA Combination Products Guidance Documents

https://www.fda.gov/RegulatoryInformation/Guidances/ucm122047.htm

9)    What are the documents required after the payment for the NDP application has been confirmed?

Answer: Kindly make an appointment with the respective officer to submit the dossier. The required documents include:

                             i.             Complete Part I (Adminsitrative documents) – hardcopy and CD.

                           ii.            Complete Part II (Drug Product) - hardcopy and CD.

                          iii.            Complete Part III (Non-clinical Documents) – CD.

                          iv.            Complete Part IV (Clinical Documents) – CD.

                           v.             9 sets of proposed package inserts and published clinical papers/ in-house synopses for the pivotal clinical studies only for new products.