SOP ON STABILITY OF FINISHED PRODUCT

1.  What

This document details the procedure for the stability of
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 finished product 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 labelled 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 implementation of SOP
03	Manager – Quality Assurance	To ensure implementation of SOP.
04	Manager – Corporate Quality Assurance	To ensure 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sampling falls on holiday(s), the sample shall be withdrawn from the stability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kept at different storage conditions shall be withdrawn at the stipulated time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:

a. 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.

b. 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.

c. 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 Quality control – Head or his designate for 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 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 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: