The file contains an idea about the Reserve sample maintenance , regulatory requirements & aspect of Reserve samples.

1. RESERVE SAMPLE
MAINTENANCE
By
Deepak
Mishra

2. Reserve sample
 Definition :
Reserve samples are the representative
samples of each Lot or batch of APIs,
Excipients, Packaging material, Intermediates
and finished products which are kept for
purpose of future reference.
 Also called Retention samples or control
samples.

3. Purpose
 Potential future evaluation of Quality of
Batches.
 Serves as a record of finished product or
starting material that can be assessed in the
event of
- Quality complaint
-a query relating to compliance with the
market authorization.
- a labeling/packaging query or a
pharmacovigilance report.

4. Reference Documents
 US: FDA
 21 CFR.170 Reserve samples
 21 CFR.180(e) Records & Reports, General
Requirements.

5. Reference Documents
 ICH
 Guideline Q7A GMP for Active Pharmaceutical
Ingredients 11.7 Reserve/Retention Samples
 EU: EC
 EU Guideline to GMP (Medicinal Products for
Human and Veterinary Use) Annexure 19 –
Reference & Retention samples.
 Chapter 6 : Quality Control – Sampling 6.12 and
6.14
 Chapter 1: Quality Management – Quality Control
1.4 (VIII).

6. Reference Documents
 WHO :
 WHO Technical report Series ,No. 863 –Thirty
fourth Report.
Sufficient samples of each batch of
Pharmaceutical Products used in studies,
together with the record of their analysis &
characteristics must be kept for reference
purposes under appropriate storage conditions
as specified in national regulations.

7. Reference Documents
 Canadian GMP Guidelines -2009 edition,
version 02, GUI-0001,
Samples C.02.025 & C.02.026

8. General Requirements
 Reserve samples should be of at least twice the
quantity necessary to perform all the required
tests except for Sterility, Pyrogen test & Bacterial
Endotoxin test.
 Reference batch of each batch of the following
must be kept at the site at which they were used :
 Starting material
 Intermediate Product
 Primary & Printed Packaging material.

9. General Requirements
 Access to these samples limited to authorized
people.
 Reserve samples to be stored in the same
intermediate container closure system in which
the item or drug product is marketed or in
which having essentially the same
characteristics.
 Quantity to be kept as per the Specification.

10. General Requirements
 Any withdrawal of retention samples to be
documented & approved by QA.
 Must be stored in a secure area under
specified storage conditions of the material or
Finish product.
 Storage condition to be monitored & any
deviation from the specified condition must be
documented, investigated & assess impact for
each retention sample.

11. General Requirements
 Records of Traceability of samples to be
maintained & be available for review by
competent authorities.
 No need to retain the reserve samples of
Rejected samples or volatile
solvents/gases/water used in manufacturing
process or hazardous materials (acid, alkalies
etc.) , flavors, liquid raw materials & excipients.

12. Drug Product(Formulation)
 Reserve sample to be collected as per
quantity specified in the individual specification
in a manner so as to cover the entire packing
of the batch.
 Reserve samples to be kept in terms of
number of units in the blister/ strip pack in
case of tablet/capsules. E.g. if 24 tablets are
required as reserve sample & each strip
containing 10 tablets then 3 strips shall be
retained as reserve sample.

13. Drug Product(Formulation)
 If Finish product re-packed with same
container closure system with same/different
art work then only one unit pack to be retained
as reserve sample.
 If product re-packed with the same container
closure system having same art work but
requires different overprinting details, only one
unit pack to be sampled as reserve sample.

14. Drug Product(Formulation)
 If product re-packed with different container
closure system, twice the quantity to be
retained as required for all tests.
 If product re-packed with same container
closure system but with different pack size,
twice the sample quantity to be retained as
required for all tests.

15. Drug Product(Formulation)
 If product re-packed in a same container
closure system with the same artwork but
analyzed again for additional tests then twice
the quantity to be retained for the test required
only.

16. APIs & Excipients
 Reserve sample to be collected from the
composite sample prepared from each batch.
 For Sterile Sodium chloride solution received
as raw materials, reserve sample to be
retained as per procedure.
 Samples to be stored in self-sealing polythene
bags in a fiberboard container.

17. APIs & Excipients
 Sample container must assure APIs and
Excipients are protected throughout the retention
period.
 Light sensitive samples to be stored in black
colored polythene bags.
 No need to keep the reserve sample for a code to
code transfer if testing is not required for the
same. If testing required as per new code , keep
single quantity for API & twice the quantity for
Excipients sufficient to perform the required test
analysis.

18. APIs & Excipients
 If only identification test or test required only
small qty then no need to keep the reserve
sample for the same.
 No need to keep the pre-shipment samples
(Purchase samples) received from Vendor for
Vendor approval.

19. Packaging Material
 In case of Printed/Primary packaging material,
one sample to be kept as reserve sample
attached to report. If not possible then to be
maintained in a dedicated place in reserve
sample room with the proper labeling under
appropriate storage conditions.
 No need to keep the sample of Corrugated
box.

20. Packaging Material
 One multi-up sheet to be collected as reserve
sample for consignments received with Multi-up
sheets.
 For those without multi-up sheets, at least one
sample from each up to be collected as reserve
sample.
 In case of STM/Reanalysis & code transfer GRN,
one checked sample to be stored as reserve
sample.

21. Storage Requirements
 Appropriate storage conditions in suitable area.
 Sufficient capacity to allow orderly storage of various
categories of materials & products.
 Proper labeling with at least following details :
o Product Name
o Batch Number
o Manufacturing/Expiry Details
o Storage conditions
o Direction for Use & Warning & Precautions if any
o Manufacturer’s Details & Address.

22. Storage Requirements
 Temperature & Humidity of the Reserve
sample Storage Area to be monitored either
with automated system or manually at least
once a day with max. & min. value.
 Calculate Mean Kinetic Temperature of
Storage area once a year using 12 month data
of Temperature records (USP <1150>). MKT
should be within the storage condition of
reserve sample.

23. Mean Kinetic Temperature
 Mean Kinetic Temperature – a useful tool to
determine the degradation of the drug
substance/product.
 A single calculated temperature which
degrades the same amount of the drug as
degraded by different temperatures during the
particular time period is called Mean Kinetic
Temperature (MKT).

24. Mean Kinetic Temperature
 Degradation of any drug depends upon
storage conditions.
 Temperature of the storage room fluctuates
from the set value. Suppose a temperature
30°C but it shall be 29.4°C , 29.8°C & 30.2°C
many times & degradation of product found 0.6
%. MKT is calculated to determine the single
temperature at which the drug would degrade
by 0.6% in that period.

25. Mean Kinetic Temperature

26. Storage Period
 Recipients
 API#
 Drug Product
 Packaging Material
 5 years from the
date of Release
 10 Years from the
date of Release
 1 year from the
Expiry date
 6 Years from the
date of Release
Category Storage Period

27. Storage Period
 Re-Analysis /Retest
and STM.
 Formulation in Bulk
Pack ##
 Formulation in Bulk
Pack having Expiry
 6 Years from the
date of Expiry.
 1.5 years from date
of Release
 1 Year from the date
of Release.
Category Storage period

28. Storage Period
 # Shelf life can be reduced for Sensitive API . Expiry of API & Drug
Product to be considered while deciding the Shelf Life.
 ## Formulation in bulk pack means drug product packed &
dispatched for further packing.
 As per EU GMP, Annexure 19, Reference & Retention samples, 3.2
Duration of Storage, Packaging material should be retained for
duration of Shelf life of Finished product concerned.
 As per EU GMP, Annexure 19, Reference & Retention samples, 3.2
Duration of Storage, Staring materials other than Solvents, Gases
or water used in manufacturing shall be retained for at least two
years after the release of Product unless no longer storage
requirement is required under the Law of Member State of
Manufacture.

29. Disposition
 Disposition as per Product Specification Procedure.
 Monitoring of Reserve samples Record after every six
months or when required.
 Approval required of QC Head before destruction of
Reserve samples.
 Destruction to be recorded in concerned register.
 Samples attached with PM report to be destroyed
along with he report destruction.

30. Thank You