ICH Guideline: Q1A (R2)

ICH Guideline: Q1A (R2) : Stability testing of new drug substances and products

ICH : International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

Brief About ICH Guideline: Q1A (R2) : Stability testing of new drug substances and products

  • Application within the three regions of the EC, Japan, and the United States.

Purpose:

To check stability testing is to provide suggestions on how the quality of a drug substance or drug product differs with time under the effect of a variety of environmental factors such as temperature, humidity, & light, and to establish a re-test period for the drug substance or shelf life for the drug product and suggest storage conditions.

Four climatic zones, I-IV as per ICH Guideline

ICH Stability Zones/ ZoneType of Climate
Zone ITemperate zone
Zone IIMediterranean/subtropical zone
Zone IIIHot dry zone
Zone IVaHot humid/tropical zone
Zone IVbHot/higher humidity
  • This guideline addresses climatic zones I and II. covered
CLIMATIC ZONES AND ASSOCIATED STORAGE
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  • General case
StudyStorage conditionMin. time period performed/covered by data at submission
Long term*25°C ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH12 months
Intermediate**30°C ± 2°C/65% RH ± 5% RH6 months
Accelerated40°C ± 2°C/75% RH ± 5% RH6 months
  • Drug substances proposed for storage in a refrigerator
StudyStorage conditionMin. time period performed/covered by data at submission
Long term*5°C ± 3°C12 months
Accelerated25°C ± 2°C/60% RH ± 5% RH6 months
  • Drug substances proposed for storage in a freezer
StudyStorage conditionMin. time period performed/covered by data at submission
Long term*– 20°C ± 5°C12 months
  • In the absence of an accelerated storage condition for drug substances (API) should be planned to store in a freezer, testing on a single batch at an elevated temperature (e.g., 5°C ± 3°C or 25°C ± 2°C) for a proper time period should be conducted to address the effect of short-term excursions outside the proposed label storage condition, e.g., during shipping or handling.
  • Data from stability studies should be on at least three primary batches of the drug product.
  • The primary batches should be of the same formulation and packaging system as proposed for marketing purposes.

Testing Frequency as per ICH Guideline

  • Long term storage condition should be every 3 months over the 1st year, every 6 months over the 2nd year, and annually subsequently through the proposed shelf life.

Time Point: 0M, 3M, 6M, 9M, 12M, 24M, 36M

  • Accelerated storage condition, a minimum of 3(three) time points, including the initial and final time points (e.g., 0M, 3M, and 6 months), from a 6-month study, is advisable.

Time Point: 0M, 3M, 6M.

  • Intermediate storage condition is called for as a result of significant change at the accelerated storage condition, a min. of four-time points, including the initial and final time points (e.g., 0, 6, 9, 12 months), from a 12- month study is advisable.

Time Point: 0M, 6M, 9M, 12M.

  • Pilot scale Batch: A batch of a drug substance or drug product mfg. by a procedure fully demonstrative of and pretending that to be applied to a full production scale batch. For solid oral dosage forms, a pilot-scale is generally, at a min., one-tenth that of a full production scale or 1 Lakh tablets or capsules, whichever is the larger.

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