Stability Study Guidance Protocol
Stability Study Guidance Protocol
1) Purpose :
1.1 To provide evidence on how the quality of drug product varies with time when
subjected to different environmental conditions, namely temperature/humidity variation
andnabling the establishment of recommended storage conditions, re-test dates and/or
shelf life.
1.2 To select the formulation / primary package to be registered for production.
1.3 To determine shelf life and storage condition of the selected formulation for prospective
production batches. 1.4 To substantiate the claimed shelf life.
2) Scope Stability study is carried out on :
2.1 Product under formulation or development.
2.2 Selected formulation for registration.
2.3 Pilot scale batch –R&D batch (10% of production batch size).
2.4 Post marketing production batch (New products) / change control products.
2.5 Stability study in cases of a change control necessity including change in composition
(API or excipients), process upon an action taken by R&D for updating purposes for re-
registration or a product upgrade.
2.6 Stability study in cases where re-work of a product falling in OOS requisites (Code:
QUI824-08), refer to Corrective & Preventive Deviation Procedures (QUP – 850 – 01) upon a
request submitted by QA/QC or production to R&D.
3) Definitions :
3.1 Long Term (real time) Testing Stability evaluation of the physical, chemical, biological,
and microbiological characteristics of a drug substance and a drug product, covering the
expected duration of the shelf life, which is claimed in the submission and will appear on the
labeling.
3.2 Accelerated Testing / intermediate testing Studies designed to increase the rate of
chemical degradation or physical change of an active drug substance or drug product by
using exaggerated storage conditions as part of the formal, definitive, storage program;
where higher temperature affect the product intermediate analysis for a longer duration at
lower temperature/ humidity conditions is allowed..
3.3 Shelf –life; Expiration Dating Period The time interval that a drug product is expected to
remain within the approved shelf-life specification provided that it is stored under the
conditions defined on the label in the proposed containers and closure.
3.4 Stress Testing These studies are undertaken to elucidate intrinsic stability characteristics
3.5 In-use stability study The purpose of in-use stability testing is to provide information for
the labelling on the preparation, storage conditions and utilization period of multidose
products after opening, reconstitution or dilution of a solution, E.g. an antibiotic injection
supplied as a powder for reconstitution
3.6 Ongoing stability studies The study carried out by the manufacturer on production
batches according to a predetermined schedule in order to monitor, confi rm and extend
the projected re-test period (or shelf-life) of the API, or confi rm or extend the shelf-life of
the FPP
. 3.7 Statements and Labeling: Storage statement is established for labeling in accordance
with the stability evaluation of the product. 3.8 Specification A list of tests, references to
analytical procedures, and appropriate acceptance criteria, which are numerical limits,
ranges or other criteria for the tests described. It establishes the set of criteria to which an
API or FPP should conform to be considered acceptable for its intended use
4) References and Related documents
4.1 ICH guidelines
4.5 Pharmaceutical statistics – practical and clinical applications – fifth edition by Sanford Bolton &
Charles Bon
5) Responsibility
6) Procedure
6.1.1 Study Set-up is typically triggered by a sample request (Form: RDF-733-15), either from the
formulation group. The Stability administrator must determine if a new study is necessary and if a
standard protocol can be used
6.1.3 Each study must carry a unique, identifying (tracking) number that will contain information
necessary to enter the study into a specific tracking system. Lot-specific information is gathered by
contacting the appropriate personnel. Alert and test schedule information is determined with input
as necessary from appropriate analytical groups.
6.1.4 The purpose of the study must also be clearly stated and must be understood by the
stability studies team, who will need to determine the impact of the study data.
6.1.5 RDF-733-15 lists information needed to initiate a stability study, stating the general
requirements needed from requester to start the study. It consists of 2 parts.
6.1.6 Part 1 should be filled by the requester of the stability study and it defines the
following
6.1.6.1 Drug Phase (Product under development / selected for registeration/post
registeration product /production batch)
6.1.2.2 Type of study (Accelerated / long term), should also mention if any in-use stability
testing is required
6.1.2.3 Product information (Product name / Dosage form / API and preservatives if
present / overages/primary package)
6.1.2.4 Selection of batches (batch no. /Mfg date for each batch to be tested)
6.1.2.5 Tested parameters (according to table no.1)
6.1.2.6 Registration procedure (old / new) These items are the requirements in order to
identi
Ensuring that the equipment used is calibrated and meets the required acceptance
criteria.
Reporting data only if the required system suitability tests pass acceptance criteria
Checking the data for compliance to specifications before discarding any test
solutions
Informing the supervisor if any unexpected results are obtained
Stopping testing if an obvious error occurs; they should not knowingly continue
testing when they expect to invalidate the data at a later time for an assignable
cause, except when the sole purpose is to see what results are obtained when
obvious errors are known. The supervisor is responsible for
Performing an objective and timely assessment.
Confirming the analyst’s knowledge and performance of correct procedures
Examining the raw data and identifying anomalous or suspect information.
Confirming the performance of the instruments.
6.20.2 Retesting
6.20.2.1 Retesting is performed using the same homogenous material as the original
sample.
6.20.2.2 The concept of retesting does not apply to some tests such as content uniformity
and dissolution.
6.20.2.3 Re-testing should not be applied over 3 times. Each testing step must be approved
and supervised by a responsible person. It is important that the retesting be performed by a
second analyst if available. Repeating testing until a passing result is obtained and then
discarding the originally obtained data is commonly referred to as testing into compliance
and is objectionable under the cGMPs.
6.20.4 Outlier Test
6.20.4.1 Outlier testing is a statistical procedure to determine if a value obtained is different
than others in a series.
6.20.4.2 The outlier test cannot be applied to data when the variability in the product is
being assessed, such as dissolution or content uniformity testing.
6.20.4.3 Dixon’s Test for Extreme Values is used to evaluate the outlier
6.20.5 When the OOS Result Is Confirmed If the investigation described above does not
identify a laboratory error as a root cause, then the OOS result is considered representative
of the lot being tested.
8) Forms
9) Records :
1-Objective:
To provide evidence of the quality of product with respect to time when subjected to
different environmental conditions, namely temperature/humidity variation, enabling the
establishment of recommended storage conditions, re-test dates and/or shelf-life.
2-Purpose:
2.1 To determine shelf-life and storage conditions for prospective production batches.
2.2 To substantiate the claimed shelf life.
3- Composition
3.1 Each …Asprin 75mg……
contains
4-Batches
7- Method of analysis
7.2 Limit
7.3 Equipment
7.4 Procedure
7.5 Calculations
The assay of ………Aspirin 75mg TAblet… as per Attachment has been tested for:
8.1 Analytical validation according to validation protocol: Accuracy Precision Specificity Quantitation
limit Detection limit Linearity and Range System suitability Robustness
. 9- Method Findings:
Refer to results tabulated in the attached tables no. ……2….. Results …………………………
PASS………………………………………
11- Conclusion
1- The product did not show any significant difference with respect to initial control analysis
regarding all physico-chemical parameters studied.
2- The product showed some significant difference with respect to the following items
…………………………………----…………………………………………………………
12-Shelf life Results from stability study of ……Aspirin 75mg…………. justifies the shelf life of ……24
months………………. for the product.