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Retention Reserve and Reference Samples

This document defines reference, retention, and reserve samples and provides requirements for storing and retaining these samples. A reference sample is stored for analyzing if needed during a batch's shelf life. A retention sample is a fully packaged finished product unit stored for identification. A reserve sample represents each lot in a shipment of an active ingredient or drug product. Requirements include storing samples in the same conditions and packaging as the product, with sufficient size for full retesting. Storage periods are specified as the shelf life plus time periods for APIs and finished products. Access is limited to authorized personnel.

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Deepak
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3K views20 pages

Retention Reserve and Reference Samples

This document defines reference, retention, and reserve samples and provides requirements for storing and retaining these samples. A reference sample is stored for analyzing if needed during a batch's shelf life. A retention sample is a fully packaged finished product unit stored for identification. A reserve sample represents each lot in a shipment of an active ingredient or drug product. Requirements include storing samples in the same conditions and packaging as the product, with sufficient size for full retesting. Storage periods are specified as the shelf life plus time periods for APIs and finished products. Access is limited to authorized personnel.

Uploaded by

Deepak
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
  • Reference, Retention, and Reserve Samples: Introduction to the document covering the basics of reference, retention, and reserve samples within pharmaceutical contexts.
  • Definitions and Descriptions: Provides detailed definitions of reference, retention, and reserve samples as applied in the EU and US regulations.
  • Scope: Specifies the application scope of guidelines across various pharmaceutical operations and subcontractors.
  • Reference Documents: Lists regulatory documents that provide the foundational rules for reference and retention samples in multiple jurisdictions.
  • General Requirements: Outlines the standard procedures and conditions required for the handling and storage of samples in pharmaceuticals.
  • API Sample Details: Details retention and storage requirements specific to API samples, addressing stability and packaging.
  • Storage and Retention: Explores storage protocols contributing to the protection and integrity of APIs and excipients.
  • Controlled Substances: Requirements for the storage and handling of controlled substances, ensuring security and compliance.
  • Reserve Samples - Finished Product: Covers the requirements for reserve samples of finished products, particularly for international markets.
  • Conclusion: Ends the document with an offer for further inquiries and a thank you note.

Reference,

Retention and
Reserve
Samples

Definition (1)
REFERENCE SAMPLE (EU):
A sample of a batch of starting material,
packaging material or finished product stored
for the purpose of being analyzed should the
need arise during the shelf life of the batch
concerned
Critical intermediate or intermediate when
sufficient stability
Sufficient size to permit
occasions full analytical

at

least

two

Definition (2)
RETENTION SAMPLE (EU):
A sample of a fully packaged unit from a
batch of finished product stored for
identification purposes
In many instances, reference and retention
samples of finished products are presented
identically.
In
such
circumstances,
reference and retention samples may be
regarded as interchangeable.

Definition (3)
RESERVE SAMPLE (US):
A sample representative of each lot in each
shipment of each active ingredient or a
sample representative of each lot of drug
product
At least two times the quantity necessary for
all tests required to determine whether the
API or drug product meets its established
specifications
Drug products must be stored in the same
container-closure in which it is marketed.

Scope
APPLICABLE TO:
All pharmaceutical manufacturing
and distribution sites
All affiliates
All GMP/GDP Subcontractors

Reference Documents (1)


EU: EC - Volume 4 GMP
Chapter 1: Quality Management
Quality Control 1.4 (VIII)
Chapter 6: Quality Control - Sampling
6.12 and 6.14
Annex 19: Reference and retention
Samples

Reference Documents (2)


US: FDA
21 CFR 211.170 Reserve Samples
21 CFR 211.180 (e) Records and
Reports, General Requirements

Reference Documents (3)


ICH
Guideline Q 7 A GMP for Active
Pharmaceutical Ingredients
paragraph 11.7 Reserve/Retention
Samples

General Requirements (1)


Requirements for retention samples (EU)
apply to reserve samples (US)
Reference/Reserve Samples should be of
sufficient size to permit, on at least two
occasions,
a
full
analytical
control
(including
sterility
and
pyrogens).
Exception must be approved by Site
Quality Management and agreed with
relevant competent authority.

General Requirements (2)


When batch is packaged in two or more
packaging operations (e.g. for different
markets),one retention sample taken from
each individual packaging operation
The exception to this will be when a small
amount of a batch is packaged for different
markets or in case of very expensive
medicinal product then only one retention
sample can be taken.

General Requirements (3)


Reference samples of each batch of the
following must be kept at the site at which
they were used:
starting material
intermediate product
primary and printed packaging material*

*The printed materials as part of the reference


and/or retention sample of the finished
product
can also be accepted as reference materials.

General Requirements (4)


Must be Stored in a secure area and under conditions
consistent with specified storage conditions for
material or finished product
Storage conditions must be recorded. In case of
deviation from specified conditions, document,
investigate and assess impact for each retention
sample
Access to these samples limited to authorized people
Quality must authorise and documented
withdrawal of any reference/retention samples.

any

API Sample Retention Period


API samples should be retained for a
time period covering API shelf-life
plus 6 years (covers potential
maximum 5 years shelf-life of
finished product)
Same retention principle generally
applies for API intermediates as
finished
product
however
the
intermediate may have a different SL
than the finished product therefore

API Storage Requirements


API samples should be stored in
same packaging system as marketed
packaging system
API intermediate samples should also
be stored in same packaging system
as marketed packaging system.

Storage Requirements for APIs,


Excipients and Packaging Materials (1)
Samples of APIs and excipients must be retained
(solvents, water, gases used in manufacturing
process are excluded)
Sample containers must assure APIs and
excipients are protected throughout the
retention period
Retention period:
Excipients and API: one year after the shelf-life of drug
product and at least two years after release of the finished
product if local regulations allow (EU)
Time period may be shortened if material stability period
is shorter.

Storage Requirements for APIs,


Excipients and Packaging Materials (2)

Retention period (cont.)


Packaging material must be retained for
the duration of shelf-life of finished
product concerned (EU regulation).

Storage Requirements for


Finished Product
Samples must be retained in marketed
primary and secondary packaging
Retention period:
Minimum one year after expiry of finished
product

Location:
Reference and Retention samples stored at
the site that releases the finished product
and/or according specific local requirements
(Canada, EU).

Storage Requirements for


Controlled Drugs
Stored separate from other samples and
protection against forced entry
Only authorised personnel must have
access to controlled drug area
Monitoring and reconciliation logbook is
mandatory, there must be a defined
retention period for logbook after the
date of last product sampling.

Reserve Samples - Finished


Product
Visual examination of representative lots of
retention (reserve) samples to be performed
if required by local regulation (products
marketed within the US or for the US market)
Examination of finished products reserve
samples
required
during
complaint
investigation and as part of Annual Product
Review (products marketed within the US or
for the US market).

Thank You
Any Questions

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