1.1.1.

Validation of Analytical Procedures

1.1.1.1. Certificates of Analysis
Comment

Check in the Y column if information is

Information
collected, confirmed, or reviewed. Check in
Y N N/A
the N column if it is not. Check in the
N/A column if it does not apply. Comments
are optional depending on data collected.

ICH Q7: Authentic Certificates of Analysis should be issued for each

batch of intermediate or API on request. Is this in compliance?

ICH Q7: Information on the name of the intermediate or API including

where appropriate its grade, the batch number, and the date of release
should be provided on the Certificate of Analysis. For intermediates or
APIs with an expiry date, the expiry date should be provided on the label
and Certificate of Analysis. For intermediates or APIs with a retest date,
the retest date should be indicated on the label and/or Certificate of
Analysis. Is this in compliance?

ICH Q7: The Certificate should list each test performed in accordance
with compendial or customer requirements, including the acceptance
limits, and the numerical results obtained (if test results are numerical).
Is this in compliance?

ICH Q7: Certificates should be dated and signed by authorized

personnel of the quality unit(s) and should show the name, address and
telephone number of the original manufacturer. Where the analysis has
been carried out by a repacker or reprocessor, the Certificate of Analysis
should show the name, address and telephone number of the
repacker/reprocessor and a reference to the name of the original
manufacturer. Is this in compliance?

ICH Q7: If new Certificates are issued by or on behalf of

repackers/reprocessors, agents or brokers, these Certificates should show
the name, address and telephone number of the laboratory that
performed the analysis. They should also contain a reference to the name
and address of the original manufacturer and to the original batch
Certificate, a copy of which should be attached. Is this in compliance?

1.1.2. Stability Monitoring

Information Comment
 Check in the Y column if information is
collected, confirmed, or reviewed. Check in
Y N N/A
the N column if it is not. Check in the
N/A column if it does not apply. Comments
are optional depending on data collected.

ICH Q7: A documented, on-going testing program should be designed

to monitor the stability characteristics of APIs, and the results should be
used to confirm appropriate storage conditions and retest or expiry dates.
Is this in compliance?

21 CFR 211.166: Stability Testing

(a) There shall be a written testing program designed to assess the

stability characteristics of drug products. The results of such stability
testing shall be used in determining appropriate storage conditions and
expiration dates. The written program shall be followed and shall
include:

(1) Sample size and test intervals based on statistical criteria for each
attribute examined to assure valid estimates of stability;

(2) Storage conditions for samples retained for testing;

(3) Reliable, meaningful, and specific test methods;

(4) Testing of the drug product in the same container-closure system as

that in which the drug product is marketed;

(5) Testing of drug products for reconstitution at the time of dispensing

(as directed in the labeling) as well as after they are reconstituted.

(b) An adequate number of batches of each drug product shall be tested

to determine an appropriate expiration date and a record of such data
shall be maintained. Accelerated studies, combined with basic stability
information on the components, drug products, and container-closure
system, may be used to support tentative expiration dates provided full
shelf life studies are not available and are being conducted. Where data
from accelerated studies are used to project a tentative expiration date
that is beyond a date supported by actual shelf life studies, there must be
stability studies conducted, including drug product testing at appropriate
intervals, until the tentative expiration date is verified or the appropriate
expiration date determined.

(c) For homeopathic drug products, the requirements of this section are
as follows:

(1) There shall be a written assessment of stability based at least on

testing or examination of the drug product for compatibility of the
ingredients, and based on marketing experience with the drug product to
indicate that there is no degradation of the product for the normal or
expected period of use.

(2) Evaluation of stability shall be based on the same container-closure

system in which the drug product is being marketed.
 Comment

Check in the Y column if information is

Information
collected, confirmed, or reviewed. Check in
Y N N/A
the N column if it is not. Check in the
N/A column if it does not apply. Comments
are optional depending on data collected.

(d) Allergenic extracts that are labeled No U.S. Standard of Potency

are exempt from the requirements of this section.

ICH Q7: The test procedures used in stability testing should be

validated and be stability indicating. Is this in compliance?

ICH Q7: Stability samples should be stored in containers that simulate

the market container. For example, if the API is marketed in bags within
fiber drums, stability samples can be packaged in bags of the same
material and in smaller-scale drums of similar or identical material
composition to the market drums. Is this in compliance?

ICH Q7: Normally the first three commercial production batches

should be placed on the stability monitoring program to confirm the
retest or expiry date. However, where data from previous studies show
that the API is expected to remain stable for at least two years, fewer
than three batches can be used. Is this in compliance?