How Much Forced Degradation in a Stress Study?


When I forcibly degrade my drug or drug product to create degradation products, how much degradation should I aim for?


The aim of a forced degradation study is to generate degradation products from a drug which are both realistic and representative, typically for the purposes of assessing degradation pathways, or to create suitable samples that will allow the development of a suitable analytical method which can be used to assess the stability of the drug throughout its shelf-life.

If too little degradation occurs then it is difficult to evaluate what might happen in real time and to develop a method which can reliably determine the amount of the degradation products which could occur.

If too much degradation occurs then there is a risk that important degradation products may be further degraded and unimportant degradation products, which would not occur on storage, may be formed.

The generally accepted industry norm for the optimal amount of degradation is between 5 and 20%, typically aiming for around  10%. Anecdotally, there is a suggestion that the 10% corresponds to the usual specification for a drug product in the US of 90 to 110% label claim.

These numbers are not quoted in regulatory guidance with the exception of the guidance from Brazil (ANVISA Resolution RDC-53/2015) which directs that results must have > 10% degradation per condition and results that are < 10% degradation, after reasonable attempt, must have scientific justification.

(Note: This article was originally posted on LinkedIn)

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