Overcoming the challenges of registration of a generic drug in Singapore

A generic product must have the same qualitative and quantitative composition in active ingredients and be of the same pharmaceutical form as a currently registered product in Singapore and shown to be bioequivalent to Singapore Reference Product (SRP). A marketing authorization application for a generic product fall under the application category of GDA-1 and GDA-2 in which the former represents strength of a registered chemical entity and usually also deemed as the one in which bioequivalence studies is conducted on and the latter is for any subsequent strength. If a generic product is not registered in any regulatory agency, the application cannot be submitted.

Whilst preparing several generic applications for companies we noted the following common challenges faced when assessment of dossier:

Administrative :

Certificate of Pharmaceutical Product(CPP) which does not state Singapore is importing country.
Letter of Authorization which has outdated company’s name and inconsistent manufacturing address not tallied with GMP certificate.

2. Bioequivalence:

Acceptance of BE reference product : No additional comparative dissolution studies was conducted between BE reference product and Singapore Reference Product to demonstrate similarity profile as most of the BE reference product is from a different manufacturing source as that registered in Singapore.
Biowaiver of subsequent strength – Unable to fulfil requirements such as dose proportionality in order to waive off the bioequivalence studies.
Acceptance of a bioequivalence studies- BE Studies conducted according to other countries guidelines and not taking into consideration SRP’s package insert dosing regimen and any additional studies required such as a multi-dose study.

Presence of ZoneIVb stability studies: ZoneIVb stability data is not available based on the number of minimum batches required for submission or from the different sites.
Patent check : Insufficient support obtained to determine the right category of patent application.

Sharing some pointers that might help you to get prepared for your filing in Singapore :

Administrative:

Ensure that CPP applied reflects Singapore as the importing country.
Letter of Authorization issued reflects the correct name ( following format of : Proprietary Name Dosage Form Strength Standard (optional) ,valid company’s name and addresses which is consistent with GMP certificate.

2.Bioequivalence:

Always check the Singapore Reference Product Manufacturing source to see whether additional comparative study is required according to Appendix 10 mentioned in part b.
Be familiar with the requirements of biowaiver in accordance to Appendix 10 Product Interchangeability and Biowaiver Request for Chemical Generic Drug Applications.
To understand the requirements in part b and ASEAN Guideline for the Conduct of Bioavailability and Bioequivalence Studies so as to map out the gaps against the existing bioequivalence study that you have on hand

3. ZoneIVb stability studies:

To be familiar with the requirements of ASEAN Guideline on Stability Study of Drug Product such as –

Critical dosage form: 3 batches with minimum of 12 months data based on ZoneIVb condition( 30°C/75%RH) and 6 months data based on accelerated storage condition (40°C/75%RH)

Non-critical dosage form: 2 batches with minimum of 6 months data based on ZoneIVb condition (30°C/75%RH) and 6 months based on accelerated storage condition (40°C/75%RH)

Patent check:

Engage the support of your manufacturer’s legal team or your own legal team to perform due diligence check regarding the patent status of the product in Singapore. Patent check is important for generic applications as it might impact upon the progress of your applications and for determine whether submission is allowable.

We hope that the above are useful for you. If there are any needs to support your generic drugs submission feel free to reach out to TRC.

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