ICH Q7
(Step 4 version, dated 10 November 2000 )
By Agung Sumantri, 2016
<11.1> General
<11.2> Testing and <11.3> Method
Validation
<11.4> CoA
<11.5> Stability Monitoring
<11.6> Expiry/ Retest Date
<11.7> Retention Samples
<11.1> General
Documentation
Required Document Approved Scientifical Aligned Aligned
ly Sound with with
registratio accepted
n filing standard
Disposition Yes
Procedures
Data recording and Yes
storage Procedures
Sampling Procedures Yes (by Quality Unit) Yes
(including sampling
plan)
Test procedures shouldYes
*Specifications (by Quality Unit)
include: Yes Yes
◦ Impurity Control (Organic,
Specifications* Yes (byInorganic, Residual Yes
Quality Unit) Solvent) Yes** Yes
◦ Microbial Limit and/ or Endotoxin (if any)
**Specifications in addition to those in the registration/filing is permitted.
<11.1> General
Out-of-Specification (OOS) Handling
OOS Handling Procedure:
◦ Investigation and Documentation
◦ Analysis of the data
◦ Assessment of impact
◦ Allocation of the tasks for corrective actions
◦ Conclusions
◦ Resampling and/or retesting
<11.1> General
Reagents and Standards
Required Procedure:
◦ Preparation of reagent/ standard solution
◦ Labeling of reagent/ standard solution
◦ Standardization and Requalification of Secondary Reference Standard
“Use by” dates (expiration) reagent/ standard solution shelf life
References Standard (RS):
◦ Primary RS
Source (documented)
Officially recognized source, no testing needed as long as stored under supplier’s
recommendations.
“in-house primary standard” (if officially recognized source is not available) Appropriate testing
should be performed to establish fully the identity and purity (documentation of this testing should
be maintained)
Storage (recorded)
Use (recorded)
◦ Secondary RS
Appropriately prepared, identified, tested, approved, and stored.
The suitability of each batch of secondary RS prior to first use (comparing against a primary RS)
Periodically re-qualified
<11.2> Testing
Each batch should be tested against its specification
Impurity Profile (note: not necessary for APIs from herbal
or animal tissue origin):
◦ Identified and Unidentified impurities
◦ identity or some qualitative analytical designation (e.g. retention
time)
◦ the range of each impurity observed
◦ classification of each identified impurity (e.g. inorganic, organic,
solvent)
The impurity profile should be compared against the
impurity profile in the regulatory submission or historical
to detect changes in raw materials, equipment, or the
production process
<11.3> Analytical Method/ Procedures should be
validated/ verified
<11.4> Certificates of Analysis
Issued for each batch
Information included:
◦ Name API (including its grade, if any)
◦ Batch number
◦ Release date
◦ Retest/ Expiry Date
Expiry date indicated on the label and Certificate of Analysis
Retest date indicated on the label and/or Certificate of Analysis
◦ List of each test (including limits, and [numerical] results)
◦ Sign and date of authorized personnel of the quality unit
◦ Name, address and telephone number of the original
manufacturer *
*If analysis is carried out by a re-packer/re-processor the CoA should show the name, address and telephone
number of the re-packer/re-processor and reference to the name of the original manufacturer
* If new Certificates are issued by or on behalf of re-packer/re-processor , agents or brokers Certificates
should show the name, address and telephone number of the laboratory that performed the analysis and
reference to original certificate and name and address of the original manufacturer (copy of original should be
attached)
<11.5> Stability Monitoring
Types:
◦ On-going at least 1 batch/ year
Frequency:
For stable API (2 years or more) Annually
For short shelf life APOI More frequent (e.g. tested monthly for the first
three months, and at three month intervals after that)
◦ Study (shelf life determination) Normally first three
commercial batches (If previous studies show stable at least for
two years, fewer than three batches can be used)
Should have stability testing program
The test procedures should be stability indicating and
validated
Stability samples should be stored in containers that
simulate the market container (same or smaller-scale
drums with identical composition)
Stability storage conditions ICH guidelines on stability.
<11.6> Expiry and Retest Dating
Common practice is to use a retest date, not an
expiration date
Definition:
◦ Expiry Date: after this date, API should not be used
◦ Retest Date: after this date, API should be re-examined to
ensure compliance with the specification
Notes (FDA Guideline):
After successful re-examination, API is used immediately
API can be retested multiple times and a different portion of the
batch used after each retest, as long as it continues to comply with
the specification.
For most biotechnological/biological substances known to be
labile, it is more appropriate to establish a shelf life than a retest
period. The same may
Notes (PhRMA Perspectives):
New retest date period Should be based on current retest
results, stability data, sound scientific principles, the retest period
filed in the NDA/DMF, and cGMP requirements
<11.7> Reserve/Retention Samples
Purpose:
◦ For future evaluation of the quality of batches of API
◦ not for future stability testing purposes
Retention Period:
◦ 1 year after the expiry date or 3 years after distribution,
whichever is the longer.
◦ For APIs with retest dates 3 years after distribution
Storage condition:
◦ The same packaging system or equivalent or more protective
than the marketed packaging system
Quantity:
◦ At least two full compendia analyses
◦ At least two full specification analyses (if not compendia)
