sop for collection storage and analysis of post production stability study
To lay down a procedure for collection, storage and analysis of post production stability study samples of various finished products.
Quality Control Supervisor.
Assistant Quality Control Manager / Quality Control Manager.
4.1 The responsibility for collection, storage, analysis of stability samples and its evaluation and
recommendations (if any) shall be followed as per flow chart
4.2 Collection of samples
4.2.1 Collection shall be done for first 3 batches for stability study in case of new products. These
samples shall be collected by QA Supervisor under instruction from Process Development Manager
4.2.2 Collection shall be done for first 3 batches for Stability study if any of the following changes has been made.
a. Change in suppliers for active ingredient (s).
b. Change in the specified manufacturing process.
c. Change in primary packing (type, size and shape).
d. Change in closure system (Lining, rubber, cap, different sterilization procedure).
e. Change in batch size.
4.2.3 For changes in formulations, following guideline shall be followed,
A. Level 1 changes
1. Definition of level
Level 1 changes are those that are unlikely to have any detectable impact on formulation quality
a. Deletion or partial deletion of an ingredient intended to affect the colour or flavour of the drug
product; or change in the ingredient of the printing ink to another approved ingredient.
b. Changes in excipients, expressed as percentage (w/w) of total formulation, less than or equal to
the following percent ranges.
The total additive effect of all excipient changes should not be more than 5 percent [Example: in a product consisting
of active ingredient A. lactose, microcrystalline cellulose and magnesium stearate, the lactose and microcrystalline
cellulose should not vary by more than an absolute total of 5 percent
Stability testing : One batch on long-term stability.
B. Level 2 changes
1. Definition of level
Level 2 changes are those that could have a significant impact on formulation quality and
a. Change in the technical grade of an excipient (Example : Avicel pH 102 versus Avicel pH 200).
b. Changes in excipients, expressed as percentage (w/w) of total formulation, greater than those
listed above for a level 1 change but less than or equal to the following percent ranges
(which represent a twofold increase over as per pharma guideline changes).
The total additive effect of all excipient changes should not change by more than 10 percent.
Stability testing : one batch with 3 months accelerated stability data and 1 batch on long-term stability.
4.2.4 Atleast one batch per year or 2% of total batches produced in a year whichever is more,
shall be kept for controlled room temperature stability study of existing products.
4.3 Sample size
4.3.1 Samples shall be collected as intact marketed pack. The quantity of samples collected shall be as per Annexure-II.
4.4 Storage of samples
4.4.1 Samples shall be kept at controlled room temperature (25 deg. +/ -2 deg.C) and Relative
4.4.2 Samples shall be kept at accelerated condition (40+/ -2 deg.C) and Relative Humidity (75+/ -5%).
Testing parameters and periodicity of analysis
4.5.1 Testing parameters and periodicity of analysis for different dosage forms shall be as per Annexure-III.
4.6 The initial analysis data shall be taken from Certificate of analysis provided the ‘Date-in’ (To) of
stability study is within the period of 15 days from date of release of the batch. In case the period
is more than 15 days the initial analysis shall be carried out once again at the time of ‘Date-in’.
4.7 If the stability assay method is different than the product release assay method,
then initial analysis shall be performed at To as per stability assay method.
4.8 Additional ‘tests [other than Product Release Specifications], if any, as per stability protocol shall be
performed at the time of ‘Date-in’ (To).
4.9 Controlled room temperature stability analysis shall be performed within -2 weeks to +4 weeks of
the due date. Accelerated stability samples shall be analysed within 5 working days of the due date.
If the samples are not taken for analysis within 5 days, same shall be stored in freezer protecting from
moisture. The frozen samples shall be analysed within 15 days.
4.10 The intact pack shall be opened at each station for analysis.
4.11 Stability indicating methods shall be followed for analysis.
4.12 The samples for stability studies shall be taken within 2 months from the date of approval of batch.
4.13 Bracketing of samples shall be done where a range of sizes of similar shaped intermediate
containers is to be evaluated if the material of composition of the container and the type of closure
are the same throughout the range. For example if a product is packed in 100’s, 200’s, 500’s and
1000’s pack, then only 100’s and 1000’s pack shall be taken for stability study provided
composition, shape and type of closure are same.
4.14 For dry powder injectables, stability study shall be carried out only on one strength preferably the
4.15 Evaluation of stability data shall be made once in a year.
Based on evaluation of data, recommendations for change of stability study parameters, analytical methods,
storage conditions etc. shall be made to R&D, CQA and Manufacturing.
4.16 During stability study any adverse change in physical parameters, pH, failing in assay or dissolution
rate shall be brought to the attention of Quality Assurance Manager, Director (Corporate Quality
Assurance), Director (Pharma Manufacturing) and Director (Pharma Research), Process Development
Manager, Director (DRA). Investigation shall be done on the affected batch alongwith all the
batches produced at the same time. Investigation shall be extended to all the ingredients used,
manufacturing process, process parameters followed and analysis at different stage.
4.17 Decision of recalling of affected batch and/or alongwith other batches produced during the same
time shall be taken by Director (Corporate Quality Assurance).