Validating active ingredients: Malaysian regulator conducts public consultation on testing
This includes potentially using an alternative method to the conventional quantitative assay tests and the circumstances in which it could be used.
The alternative method that the National Pharmaceutical Regulatory Agency (NPRA) has proposed is Quantification By Input (QBI) and could be used when it is not feasible to conduct the quantitative assay test.
The NPRA supervises traditional and complementary medicine (T&CM) in the form of finished products across the entire process encompassing registration, manufacturing, importing, distribution, prescription, and post-marketing surveillance.
The public consultation, which is now at the final stage, will end on July 17.
The draft was previously distributed to the industry body Malaysian Dietary Supplement Association (MADSA) and Malaysian Organisation of Pharmaceutical Industries (MOPI) for comments and feedback.
When is assay test not needed?
Based on NPRA’s proposal, finished product manufacturers are not required to do assay test if there is no quantitative claim made for the active ingredient on the product label.
However, if a quantitative claim of a specific compound in the active ingredient is being made, an assay test will be required – provided if there is a method to do so.
For instance, a product claiming to contain 50mg of marigold extract (active ingredient) providing 10mg of lutein (specific compound) and 2mg of zeaxanthin (specific compound) will require assay test to validate the amount of lutein and zeaxanthin.
Products containing active ingredients in the isolated form is also required to conduct assay test.
For example, if the product claims to contain 10mg of lutein as the active ingredient, then assay test will be required.
If there is no suitable method, the QBI could be allowed.
Also, if the assay result of active ingredient is difficult or unable to be achieved due to factors such as interference between ingredients, QBI can be allowed and a scientific justification should be provided.
The NPRA has provided a flowchart to help companies determine if an assay test or QBI is needed.
Once a product meets the criteria for using QBI, the words ‘Not assayed. Quantified by Input’ or wording with similar meaning may be used for the active ingredient on the certificate of analysis of the finished product and stability data.
What is QBI?
The Quantification By Input (QBI) means that the content of an active ingredient is estimated from the amount dispensed during the manufacturing of the product.
The NPRA is also proposing that the QBI method can only be applied to finished products made in a facility compliant to Malaysian Guidelines on Good Manufacturing Practice for Traditional Medicines and Health Supplements, 1st Ed, 2008.
Allowing the use of QBI has been deemed as very helpful as assay tests for active ingredients have been a challenge for health supplements, especially multi active ingredients and complex botanical ingredients, due to interference from other ingredients.
The NPRA has referred to overseas procedures, such as Australia’s Therapeutic Goods Administrations’ “Guidance on the use of the term ‘Quantified by Input’ for listed complementary medicines (Revised October 2009)” and Health Canada’s Quality of Natural Health Products Guide in the drafting of the guidance.
It is a requirement for companies to conduct quantitative assay test for all active ingredients claimed on the label of their health supplements and natural products when registering them with the Malaysian authorities.
This is according to the revised Malaysian Drug Registration Guidance Document (DRGD) published in January.
However, the challenge is that quantitative assay tests may not be possible or practical to achieve in some cases.
Thus, the NPRA has proposed to consider allowing the QBI method when testing the active ingredients claimed on traditional medicines and health supplements.