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SOP ON STABILITY OF FINISHED PRODUCTS

1. What

This document details the procedure for the stability of the finished product to be carried out in ABC Pharmaceuticals

2. Why

It is the policy of ABC Pharmaceuticals that a written procedure shall be followed for the stability studies of the finished products to assure the efficacy and safety of the drug products manufactured by ABC Pharmaceuticals throughout the shelf life of the products and products remain within specifications under the labeled storage conditions to meet the regulatory requirements.

3. When

This procedure is to be applied at the time of manufacturing of new formulation in the company and its routine observation and but not limited to:

i) Major deviation in process

ii) New equipments

iii) New sources of raw material

iv) hange in primary packing material

v) One batch annually

4. RESPONSIBILITY

Persons along with their responsibilities are given below:

S. No	Designation	Responsibility
01	Executive – Corporate Quality Assurance	To prepare and follow the SOP accordingly. Maintain the record as per SOP.
02	Manager – Quality Control	To ensure the implementation of SOP
03	Manager – Quality Assurance	To ensure implementation of SOP.
04	Manager – Corporate Quality Assurance	To ensure the implementation of SOP

5. PROCEDURE

5.1 GENERAL

5.1.1 “Initial” (Zero) month shall be defined as “date of testing of finished product sample” and in case product is packed for stability purpose, prior to actual packing operation, the date of testing will be considered as initial (zero) month.

5.1.2 Sample shall be incorporated into the stability programme at all storage conditions (as applicable) on the same date.

5.1.3 In case the sampling falls on holiday(s), the sample shall be withdrawn from the stability chamber / storage conditions on next working day.

5.1.4 The samples kept at different storage conditions shall be withdrawn at the stipulated time interval and to be analysed within 15 days. During this period the sample shall be stored in refrigerator at 2ºC to 8ºC.

5.2 PURPOSE OF STABILITY STUDIES

5.2.1 To understand any chemical/ physical changes occur to the formulation due to the exposure of different environmental conditions.

5.2.2 To confirm that Drug Products are assured for their efficacy and safety in marketed packs throughout the cycle of warehousing, distribution, storage and uses.

5.2.3 To compile data for confirming the storage conditions, retest period and shelf life.

5.2.4 To monitor the impact of any chemical or physical change(s) in manufacturing process and/or Excipients on products quality

5.2.5 To support and assured the Drug products registration in different countries.

5.3 REGULAR STABILITY STUDIES

5.3.1 Long term stability studies shall be done at two different storage conditions for shelf life, considering the climatic zones.

I) Temperature : 25 ± 2ºC

Relative Humidity : 60 ± 5%

II)Temperature : 30 ± 2ºC (Intermediate Condition for Zone I & II)

Relative Humidity : 65 ± 5%

5.3.2 Intermediate stability data for climatic zone I & II shall be collected from long term stability data of climatic zone III & IV (if required)

5.3.3 Accelerated stability study shall be done at following storage condition up to six months.

Temperature : 40 ± 2ºC

Relative Humidity : 75 ± 5%

5.3.4 Storage period for stability studies can be extended after shelf life, which shall be addressed in specific protocol(s).

5.3.5 Initial optimisation and validation batches and subsequently minimum one batch (preferably first batch of the year) per year shall be subjected for stability studies (“Initially” means the product is subjected for stability for the first time at the location).

5.3.6 Products for initial stability studies shall be subjected for long term and/or Intermediate and accelerated stability studies, depending upon their market (Zone Wise) for which the product is manufactured.

5.3.7 Products for subsequent ongoing stability studies shall be subjected for long term stability studies, depending upon their market (Zone Wise) to which the product is manufactured.

5.3.8 Q.A. department shall ensure that these samples are packed in simulated market packing.

5.3.9 Sample quantity shall be sufficient to carry out repeat analysis as per the scheduled frequencies at different storage condition.

5.3.10 A sampling schedule prepared and fresh samples shall be included as and when required.

5.3.11 The samples shall be analysed for the different parameters as per the guidelines given in the protocol (product specific).

5.3.12 In case of long-term stability studies, the sample shall be analysed at an interval of 3 months, 6 months, 9 months, 12 months, 18 months, 24 months and annually thereafter till the shelf life of a specific product.

5.3.13 The long term stability data of Zone III & IV (Temperature 30oC + 2oC & RH 65 % + 5%) at an interval of 3 months, 6 months, 9 months, 12 months and also considered for intermediate stability study of Zone I & II.

5.3.14 In case of accelerated stability studies samples shall be analysed at an interval of 3 months and 6 months.

5.3.15 The stability studies shall be discontinued if there shall be any loss of chemical purity / potency / efficacy / safety of the product as observed after analysis and reviewing the analytical results, by technical committee, below the acceptable criteria as per the respective specification.

5.4 ADDITIONAL NEED-BASED STABILITY STUDIES

5.4.1 Stress Testing

5.4.1.1 Additional stability studies under stress conditions shall be done (if required) to check the stability of the drug products.

5.4.1.2 The following conditions are suggested for stress testing of drug products:

Increments of 5°C or 10°C higher than accelerated temperature of 40°C to cover the studies of influence of dry heat on drug products. This test is to simulate hot conditions faced by drug products during transportation and shipment.
Simultaneous exposure to 40°C and a minimum of 1.2 million lux h fluorescent light and 200W h/m2 UV light. This test is meant to study the influence of tropical conditions on the drug products.
Any other storage conditions specified by regulatory authorities or any tie up companies.

5.4.1.3 The stress testing shall be done on a single and initial batch of a product, which must be of the same formulation and quality as the marketing product, including the packaging.

5.4.1.4 The stress testing shall be conducted at the time interval of 1 month, 2 months and 3 months.

5.4.1.5 The samples shall be observed for physical/ chemical changes at a regular interval of about 15 days and sampling shall be done on monthly basis.

5.4.2 Additional stability studies shall be done in case (but not limited) of major deviation in process, new equipments, new sources of raw material and/or change in primary packing material but depth of studies like no. of batches, storage condition(s) shall be decided based on risk assessment.

5.4.3 Additional stability studies shall carried out for the same batches kept for regular stability studies beyond the stipulated time intervals / conditions as per the directives received from Tie Up Company or location Quality – Head or his designate.

5.4.4 Additional stability studies shall be carried out as per the customer’s requirement based on the storage conditions and the frequencies of analysis as given by the customer.

5.4.5 Additional stability studies shall be carried out as per the directions received from “Change Control Committee”

5.4.6 Additional stability studies shall be carried out as per requirement of Tie Up Company or direction of Regulatory agencies(s) at any other specified temperature and RH conditions.

5.5 SAMPLING

5.5.1 The IPQA(In-process Quality Assurance) personnel shall collect the product samples for stability studies from optimisation and validation batches and subsequently minimum one batch (preferably first batch of the year) per year including all different packing like blisters, strips and/or containers etc shall be considered.

5.5.2 QA department shall inform the warehouse in-charge for stability plan with product name, batch number and sample quantity. IPQA personnel shall collect the stability sample from warehouse.

5.5.3 QA department shall label the stability samples individually with colored labels specified as per Labelling Policy.

5.5.4 QA department shall put the samples at different storage conditions in stability chambers and maintain the storage record on Finished Product Stability Sample Storage Record (Appendix I).

5.5.5 Withdraw the samples as per the schedule and maintain the record on Accelerated Stability Withdrawal Record (Appendix II) and Long Term Stability Withdrawal Record (Appendix III)

5.6 Bracketing of product

5.6.1 In case the product has identical formulation but there are different packing configurations with same primary packing material, then any one type of packing configuration shall be chosen and samples shall be collected.

5.6.2 If product is manufactured under different brand names but the formulation, strength and manufacturing process remains same with same primary packing materials then samples of any one brand name shall be collected.

5.7 DOCUMENTATION

5.7.1 Maintain the record for storage and withdrawal of finished product stability samples as per the respective appendix.

5.7.2 A monthly schedule shall be prepared on Annexure II and send a copy of the same to Quality control – Head.

5.7.3 Send the information to Quality control – Head for storage of the stability sample with details like product name, mfg. date, expiry date, sample quantity, date of collection, storage conditions and stability intervals on Appendix II and/or Appendix III depending upon their requirement.

5.7.4 A calendar for stability study shall be prepared by quality control department for the products undergoing stability studies.

5.7.5 A stability study protocol shall be prepared and studies shall be executed accordingly.

5.7.6 A logbook for receiving and issuance of stability samples shall be maintained by the quality control department.

5.7.7 The raw data of analytical studies of stability products shall be recorded in test protocol.

5.7.8 After completion of the study, the results shall be summarized on product-specific Appendix(s) i.e. Appendix-II Accelerated Stability Withdrawal Record and Appendix-III Long Term Stability Withdrawal Record.

5.8 GENERAL INSTRUCTIONS

5.8.1 Analytical reports and supporting data like chromatograms/charts/graphs, etc. shall be cross-checked by the Quality control – Head or his designate for the correctness of results, calculations, formulae used for calculating results, analytical findings, and observations and shall be counter-signed.

5.8.2 Unusual observations shall be highlighted in the report and shall be informed to Tie Up Company and/or Regulatory agency with necessary details.

5.8.3 Composite data shall be prepared at the time of submission as per the requirement of that company.

APPENDIX I

FINISHED PRODUCT STABILITY SAMPLE STORAGE RECORD

APPENDIX II

ACCELERATED STABILITY WITHDRAWAL RECORD

SAMPLE STORED AT : 40° C ± 2ºC AND 75% ± 5% RH.

APPENDIX III

LONG TERM STABILITY WITHDRAWAL RECORD

SAMPLE STORED AT:

Product
B.No.
Qty.
Mfg
Exp
Date of sample storage
Withdrawal details (Date)	3 months
	By
	6 months
	By
	9 months
	By
	12 months
	By
	18 months
	By
	24 months
	By
	36 months
	By
Remarks