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Limit of related substances

what is the general limits for related substances in drug products …and what is the guidelines for that limit?

Degradation products present at a level of not more than (≤) the identification threshold generally Thresholds for degradation products are expressed either as a percentage of the drug substance or as total daily intake (TDI) of the degradation product. Lower thresholds can be appropriate if the degradation product is unusually toxic. Higher thresholds should be scientifically justified. Analytical procedures should be developed for those degradation products that are suspected to be unusually potent, producing toxic or significant pharmacological effects at levels not more than (≤) the identification threshold. In unusual circumstances, technical factors (e.g., manufacturing capability, a low drug substance to excipient ratio, or the use of excipients that are crude products of animal or plant origin) can be considered as part of the justification for selection of alternative thresholds based upon manufacturing experience with the proposed commercial process.

Attachment 1: Thresholds for Degradation Products in New Drug Products
Reporting Thresholds
Maximum Daily Dose1
Threshold2,3
≤ 1 g
0.1%

1 g
0.05%
Identification Thresholds
Maximum Daily Dose1
Threshold2, 3
< 1 mg
1.0% or 5 μg TDI, whichever is lower
1 mg - 10 mg
0.5% or 20 μg TDI, whichever is lower
10 mg - 2 g
0.2% or 2 mg TDI, whichever is lower
2 g
0.10%
Qualification Thresholds
Maximum Daily Dose1
Threshold2,3
< 10 mg
1.0% or 50 μg TDI, whichever is lower
10 mg - 100 mg
0.5% or 200 μg TDI, whichever is lower
100 mg - 2 g
0.2% or 3 mg TDI, whichever is lower
2 g
0.15%

Reference: ICH HARMONISED TRIPARTITE GUIDELINE
IMPURITIES IN NEW DRUG PRODUCTS
Q3B(R2)
Current Step 4 version
dated 2 June 2006

Thanks Mr Shahid Ali for your reply and my pleased to contact with you later