Pharmaceutical Stability Studies are essential for demonstrating that a drug product maintains its quality, safety, and efficacy throughout its intended shelf life.
Purpose of Pharmaceutical Stability Studies
Purpose for conducting stability studies of finished pharmaceutical products to evaluate their shelf life and storage conditions, in accordance with WHO guidelines and applicable regulatory requirements.
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Scope :
This SOP is applicable for procedure for Stability Study of Products in your company.
Roles and Responsibilities:
| DESIGNATION | RESPONSIBILITIES |
| Officer/Executive Production | To Provide the batches for stability studies. To raise the intimation of stability samples. |
| Officer / Executive OfQuality Assurance Department | Ensures environmental conditions of chambers are within specified limits. To review the raw data and stability study data. To maintain all stability Study records. To ensure timely withdrawal of stability samples. To maintain all records for loading & withdrawal of stability samples with proper status labeling. To prepare and check the SOP. To review stability protocols and reports. To Review the stability summary of respective product. Collection of stability samples as per approved Stability Study protocol. To carry out Investigation of OOS & OOT |
| DESIGNATION | RESPONSIBILITIES |
| Analyst/Officer/ Executive Of Quality Control | To prepare stability study protocol. To conducts stability testing as per the approved protocol. To ensure timely analysis of stability study samples. To maintain the raw data & various analytical records. To inform the out of specification (OOS) / Out of trend (OOT) results. To prepare & review the Stability Summary of respective product. |
| Officer/ Executive of Engineering | To carry out the preventive maintenance and calibration of stability chambers as per schedule. |
| Head of Quality Assurance/Designee) Quality Assurance | Approval of stability study protocols and reports To approve Deviation and OOS Investigation & regulatory support and communication To approve any change control (if required) Responsible for Training and supervision To approve the stability summary. |
Procedure for Pharmaceutical Stability Studies:
Definitions:
Stability: The capacity of a drug product to comply with the specifications laid down for the duration of the shelf life assigned to it, when stored under the conditions stated on the label of the containers/ packs.
Stability study stations/ Time points: Stability study stations are the due dates by which stability study samples are to be withdrawn from the stability study chambers.
Shelf life: The time period during which a drug product is expected to remain within the approved shelf life specification provided that it is stored as per the conditions defined on the label.
Release specification: The combination of the physical-chemical, and microbiological tests and acceptance criteria to determine the suitability of a drug product at the time of release.
Stability study specification: The combination of physical-chemical, and microbiological tests and acceptance criteria to determine the suitability of a drug product throughout its shelf life.
Photo stability study: Photo stability is the capacity of a drug molecule product to remain intact and unaffected on light exposure and does not result in unacceptable change.
Selection of Batches for Stability Studies
First three validation batches / commercial batches of new product shall be kept for real time and accelerated stability studies. After that minimum one batch shall be kept every year for real time stability study.
The stability study shall be conducted to support any QMS document (deviation, change control, CAPA, OOS/ OOT, risk assessment, Annual product review) as evaluated by Head QA or cross-functional team.
Batches for stability study shall be selected on the basis of the below criteria:
| S. No. | Category | Selected Batches* | Stability condition | |
| 01 | New product | 03 initial batches | ASS | RSS |
| 02 | Change in formulation | 03 initial batches after revision | ASS | RSS |
| 03 | Change in manufacturing process | 03 initial batches after revision | ASS | RSS |
| 04 | Change in manufacturing equipment (with different design and operational principle) | 03 initial batches after revision | ASS | RSS |
| 05 | Change in API source | 03 batch after revision | ASS | RSS |
| 06 | Change in primary packing material | 03batches after revision | ASS | RSS |
| 07 | Change in primary packing configuration (but no change in packing material) | 01batch after revision | ASS | — |
| 08 | Change in functional excipient source | 01batch after revision | ASS | — |
| 09 | Change in batch size | 01batch after revision | — | RSS |
| 10 | Follow up batches | 01batch annually | — | RSS |
Concern person from QA shall charge stability sample and enter details in stability sample charging logbook.
Samples for stability shall be charged in its actual or proposed marketing pack and shall be labeled with respective condition label before charging different colors as follows-
Storage Condition Label color Format of label Stability study condition
40°C ±2°C / 75% RH ±5% For Accelerated Study
30°C ±2°C / 75% RH ± 5% RH For Real Time Study
30°C ± 2°C / 65% RH ± 5% RH Intermediate Study
25°C ±2°C / 60% RH ±5% RH For Real Time Study
Additional Sample quantity shall be incubated in accelerated and Real time (Long term) condition, equivalent to one stability study station quantities for chemical and one stability station quantity for microbiology analysis.
After charging of respective stability sample, charging and schedule withdrawal details shall be updated in stability master schedule.
If a batch has to be kept for stability study, after 30 days of analysis, a zero-time analysis shall be done again before putting for stability.
Stability storage conditions for Pharmaceutical Stability Studies
Following real time and accelerated study the storage conditions shall be followed-
| Climatic Zone | Accelerated Storage Conditions | Long Term Storage Conditions | ||
| Temperature | Humidity | Temperature | Humidity | |
| Zone II | 40ºC ± 2ºC | 75% ± 5% RH | 25ºC ± 2ºC | 60% ± 5% RH |
| Zone IVa | 40ºC ± 2ºC | 75% ± 5% RH | 30ºC ± 2ºC | 65% ± 5% RH |
| Zone IV b | 40ºC ± 2ºC | 75% ± 5% RH | 30ºC ± 2ºC | 75% ± 5% RH |
All domestic and export products shall be stored as per the condition mentioned for zone IV b in above table.
Storage period for stability studies can be extended beyond shelf life, which shall be addressed in specific protocol.
Different type of stability study i. e In-use, freeze-thaw, photo-stability and other stability study shall be performed as per respective stability protocol
Monitoring Stability Chamber – Pharmaceutical Stability Studies:
System generated report of temperature and humidity shall be maintained once in 24hours, and verified for any discrepancy.
In case, print not generated from system due to any discrepancy, temperature and humidity shall be recorded thrice a day manually in Temperature and Humidity record for stability chamber.
Mean kinetic temperature/ RH data shall be taken out from the stability software on daily basis and should not deviate by ± 2ºC and ± 5% respectively from the set value.
In case any deviation observed in the recommended temperature or RH, QA shall take immediate action to rectify the equipment malfunctioning.
Short term spikes / excursion due to opening of door of the chambers are accepted as unavoidable.
Temporary excursions due to equipment failure shall be addressed and reported. Such incidences shall be informed to Engineering department through work order. It is acceptable to have excursions up to 4 hours continuously. It is also acceptable if excursions are occurred intermittently but not more than 1 hour continuously. But if excursion is more than 4 hours continuously but less than 24 hours It shall be addressed as Incident.
Stability Chambers excursion management in Pharmaceutical Stability Studies
Categorize excursions in two types
Temporary Excursion
Excursion more than 4 hours continuous but less than 24 hours
Humidity control system overshoots.
Probe condensation following door opening
Sensor response lag
Door opening for loading and unloading the samples
Brief power failure/ power fluctuation
Room environmental influence
Water level adjustment in Humidity tank.
Major Excursion
Air circulation disturbance
Excursion more than 24 hours continuous.
Excursion Acceptance Criteria
Excursion more than 4 hours continuous but less than 24 hours.
If the error related to stability chamber cannot be rectified within 24 hours, the stability samples shall be shifted to back up chamber.
Excursions that return to set limits within a short duration may be considered acceptable.
The chamber should return to the specified temperature and RH limits automatically without manual intervention.
The cause of excursion should be known and justifiable, such as door opening, compressor cycling, or sample loading.
The trend graph records should show that conditions stabilized and remained within limits after the excursion.
Based on duration of excursion, QA assessment should confirm no impact on product quality or stability study results.
The excursion should not occur frequently. Repeated excursions may indicate equipment or operational issues.
The excursion must be documented in the chamber excursion logbook including time, duration and reason.
Excursion Incident Investigation
Temperature or RH exceeds acceptable limits.
Excursion lasts more than the defined duration.
Chamber fails to return to normal conditions.
Equipment malfunction is suspected.
Power failure affecting chamber conditions.
Excursion caused by human error, such as door not closed properly or incorrect sample handling.
This shall be documented in a deviation report, evaluated and approved by Head QA/ Designee.
In case of any deviation, if the error related to stability chamber is not rectified within 24 hours and backup chamber is also not available, then after 24 hours, the most sensitive products for temperature/RH shall be analyzed to know the impact of deviation on other products under stability.
Chamber opening record shall be maintained.
Stability Sample Withdrawal Procedure
Monthly Withdrawal Schedule
Stability monthly schedule shall be prepare, according to stability master schedule, Sample withdrawal details shall be mentioned in monthly schedule.
Sample withdrawal for stability testing from particular chamber shall be done as per monthly Schedule.
Sample withdrawal frequency shall be + 2 days. If the holiday comes more than 2 days then sample shall be withdraw on next working day.
Sample Reconciliation
After withdrawal of stability sample, sample withdrawal details shall be entered in Stability sample Reconciliation form.
Sample Handling
Sample for chemical analysis shall be handover to QC Lab and for Microbial Enumeration Test & Test for specified micro-organism samples are to be handover to the microbiologist of Micro Labs.
QC Executive/ designee shall record the entry for stability product for analysis.
Stability Testing Frequency:
Accelerated stability Schedule:
At intervals of 3 months & 6 months.
Long-Term Stability Schedule:
At intervals of 03 months during the first year, at intervals of 06 months during the second Year and every 12 months thereafter up to the proposed shelf life. Stability studies shall be carried out 1 year beyond the proposed shelf life.
Stability Studies Initiation
Three batches, if new formulation is manufactured.
Three batches, if formulation is changed.
Three batches, if primary packaging component is changed.
Three batches, if any significant change in the manufacturing process.
Three batches, if any significant change in manufacturing equipment, which could have an impact on product quality.
Three batches, if manufacturing site is change.
One batch, if source of active raw materials are changed.
One batch annually, for routine monitoring.
Products for initial stability studies shall be subjected for long term and accelerated stability studies, depending upon market (Zone Wise) for which the product is manufactured.
For new products, first three batches of finished product in simulated containers closures to be used for marketing shall be kept for stability studies.
Study Testing Frequencies
Accelerated Stability Schedule
New Products 40°C ± 2°C, 75% ± 5% RH 0, 3, 6 Months
Long-Term Stability Schedule
New Products 30°C ± 2°C, 75% ± 5% RH 0, 3, 6, 9, 12, 18, 24, 36, 48 Months
Routine products 30°C ± 2°C, 75% ± 5% RH 0, 3, 6, 9, 12, 18, 24, 36, 48 Months
Bracketing of product in Pharmaceutical Stability Studies:
If product is manufactured under different brand names but the formulation, strength and manufacturing process remain same with same primary packing materials then samples of any one brand name shall be collected.
Stability Indicating Methods
Stress testing
One batch of each product shall be selected for stress testing.
The following conditions are suggested for stress testing of drug products:
Increments of 20°C higher than accelerated temperature of 40°C to cover study of the influence of dry heat for one week. This test is to stimulate hot conditions faced by products during transportation and shipment.
Photostability
Samples shall be exposed to light providing an overall illumination of not less than 1.2 million lux hours and an integrated near ultraviolet energy of not less than 200 watt hours/square meter
Assay of the all treated sample shall be recorded.
Compare the chromatogram of the standard preparation with sample preparation.
Any other impurity developed due to the force degradation of product shall be recorded.
Any degradation product developed shall be treated as indicator of degradation of product during stability study of product.
All the Raw Data shall be recorded into the respective laboratory notebook/Stability Work sheet at the time of analysis as per respective SOP. Analyze samples as per the stability protocol for the particular stability time stations. Use specified standard test procedure mentioned in the stability protocol for analyzing stability samples at all-time stations, for analytical tests performed, unless otherwise use the specified specification limits as per stability protocol.
A ±5% decrease in assay from its initial value, or failure to meet acceptance criteria for potency in case of biological and microbiological assay.
Related Substances/Degradation Products–exceeding its acceptance criteria.
Failure to meet the acceptance criteria for description..
Loss of water in semi permeable containers change more than 5% of initial value.
Report the information about significant changes to Quality Assurance. If any aberrant result is observed, perform investigation.
If analysis of stability samples is to be performed at an outside laboratory, ensure that the same is approved by QA.
If the product does not comply with respect to laid down standards or specification at 40°C ± 2°C, 75% ± 5% condition the studies are continued at 30°C ± 2°C, 75% ± 5% RH.
Safety Precautions During Pharmaceutical Stability Studies
Personal Protective Equipment (PPE)
Wear a laboratory coat, gloves, and safety goggles while handling stability samples and chemicals.
Follow site-specific PPE requirements.
Safe Handling of Stability Samples
Ensure samples remain in their original approved packaging whenever possible.
Handle samples carefully to prevent contamination, mix-ups, or physical damage.
Reference Taken
Acronyms Used :
QA : Quality Assurance
QC : Quality Control
SOP : Standard Operating Procedure
No. : Number
RH Relative Humidity
IPQA : In process Quality Assurance
STP : Standard Testing Procedure
HPLC : High-Performance Liquid Chromatography
OOS : Out of Specification
OOT : Out of Trend
Frequently Asked Questions (FAQs)
Q-1 What is a stability study in pharmaceuticals?
Answer: A stability study describe how the quality, safety, and efficacy of a pharmaceutical product change over time under defined environmental conditions.
Q-2 Why are stability studies important?
Answer: Stability studies ensure that a pharmaceutical product remains within its approved specifications throughout its shelf life.
Q-3 What are the different types of stability studies?
Answer: The main types of stability studies include:
- Long-term (Real-Time) Stability Study
- Accelerated Stability Study
- Intermediate Stability Study
- Photostability Study
- Stress Stability
Q-4 What is the difference between long-term and accelerated stability studies?
Answer: Long-term stability studies evaluate products under normal storage conditions throughout their shelf life, while accelerated stability studies expose products to elevated temperature and humidity to predict stability in a shorter period.