FAQ Variation on Medical Device-Drug Combination Products

FAQs: Variation On Medical Device-Drug Combination Products

1. Variation procedure for a registered combination product

Kindly refer to 6.0 Post Approval Changes/ Variation To Particulars Of A Registered Combination Product, Guideline for Registration of Drug-Medical Device and Medical Device-Drug Combination Products available at here.

Variation application should be submitted along with a cover letter which includes the following:

Brief description of the proposed variation with justification
Current and proposed change of information in tabulated format
A declaration which is undersigned by the Product Registration Holder that declares:
- There is no other change except for the proposed variation;
- The required supporting documents as specified for the variation have been submitted; and
- All of the conditions have been fulfilled based on the proposed category

2. Where shall the applicant submit the required documents?

Application for changes/variation of ancillary drug component for a registered medical device-drug combination product along with Appendix 4: Application Form for Post-Approval Changes/ Variation of Ancillary Components for Combination Products and supporting documents shall be submitted to NPRA manually to:

Product & Cosmetic Regulatory Coordination Section,
Centre of Regulatory Coordination & Strategic Planning,
National Pharmaceutical Regulatory Agency,
Lot 36, Jalan Universiti (Jalan Profesor Diraja Ungku Aziz),
46200 Petaling Jaya, Selangor

3. What are the documents required to be submitted for additional/ replacement of the manufacturing site of drug substance?

Addition/Replacement of manufacturing site of drug substance

1. Specification of drug substance remains unchanged.

2. Test procedures remain the same, or changes in the test procedure are minor.

3. If there are changes to the specification of drug substance, variation for change of specification of drug substance is also applicable.

1. Manufacturer’s name and address.

2. GMP certificate or any other evidence of GMP compliance from a regulatory authority.

3. Nomenclature, structure, general properties of drug substance.

4. Specification of drug substance.

5. CoA (2 batches) of the drug substance.

6. Comparative tabulated format of the specification and results of COA for drug substances (2 batches) from the proposed manufacturing site – Refer Table 1 below.

Table 1: Comparative tabulated format of the specification and COA of drug substance from the proposed manufacturing site

Proposed Specification		Results of COA
Test parameter	Limit	Batch 1	Batch 2

4. What are the documents required to be submitted for Change of specification of drug substance?

Change of specification of drug substance

1. Test procedures remain the same, or changes in the test procedure are minor.

2. The change should not be the result of unexpected events arising during manufacture or because of stability concerns.

1. Revised specification of drug substance.

2. CoA (2 batches) of the drug substance for all tests in the proposed specification.

3.Comparative tabulated format of the specification and results of COA for drug substances (2 batches) from the proposed manufacturing site – Refer Table 1 below.

4. Comparative tabulated format of the approved and proposed specification of drug substance with changes highlighted – Refer Table 2 below.

5. Technical justification for the proposed changes.

Table 1: Comparative tabulated format of the specification and results of COA for drug substances (2 batches) from the proposed manufacturing site

Proposed Specification		Results of COA
Test parameter	Limit	Batch 1	Batch 2

Table 2: Comparative tabulated format of the approved and proposed specifications of drug substance with changes highlighted

Approved Specification		Proposed Specification		Technical justification for the proposed changes
Test parameter	Limit	Test parameter	Limit

5. What are the documents required to be submitted for Change of name and/or address of the manufacturer of drug substance?

Change of name and/or address of the manufacturer of drug substance

The manufacturing site of drug substance remains the same.
No other changes except for the change of the name and/or address of the manufacturer of drug substance (e.g. postal code, street name, district/state name).

Updated information of the manufacturer of the drug substance.
Official document/evidence (where applicable).

6. What is the validity period of the endorsement letter issued for variation of a particular ancillary component?

The current policy stipulates the validity period of endorsement letter shall be in line with the validity period of combination product registration.

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