This
document details the procedure for the stability of the finished product to be
carried out in XYZ Limited. It is the policy of XYZ Limited 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 XYZ Limited,
by the client, or by a tie-up company throughout the shelf life of the products
and products remain within specifications under the labeled storage conditions
to meet the regulatory requirements.
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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:
Major
deviation in the process
New
equipment
New
sources of raw material
Change
in primary packing material
One
batch annually
RESPONSIBILITY
Persons
along with their responsibilities are given below:
Executive
- Corporate Quality Assurance:- To prepare the SOP. Maintain the record as per
SOP.
Trainee
Analyst/ Jr. Analyst/ Analyst/ Sr. Analyst:- To follow the SOP accordingly
Manager -Quality
Control/ Quality Assurance:- To ensure implementation of SOP
General
Manager – Technical:- To ensure implementation of SOP
Procedure Of stability studies of finished goods
GENERAL
“Initial” (Zero) month shall be defined as “date of
testing of finished product sample” and in case the product is packed for
stability purposes, prior to actual packing operation, the date of testing will
be considered as initial (zero) month.
A sample shall be incorporated into the stability program
at all storage conditions (as applicable) on the same date.
In case the sampling falls on a holiday(s), the sample
shall be withdrawn from the stability chamber/storage conditions on the next
working day.
The samples kept at different storage conditions shall be withdrawn at the stipulated time interval and to be analyzed within 15 days ( in case of long-term stability) and within 7 days (in case of accelerated stability). During this period the sample shall be stored in a refrigerator from 2ºC to 8ºC.
PURPOSE OF STABILITY STUDIES
To
understand any chemical/ physical changes that occur to the formulation due to
the exposure to different environmental conditions.
To
confirm that Drug Products are assured for their efficacy and safety in
marketed packs throughout the cycle of warehousing, distribution, storage, and
uses.
To
compile data for confirming the storage conditions, retest period and shelf
life.
To
monitor the impact of any chemical or physical change(s) in the manufacturing
process and/or Recipients on products quality
To
support and assured the Drug products registration in different countries.
Accelerated stability studies
Long-term stability studies shall be done at 30˚ C + 2˚C / 65 + 5%
Rh
conditions for shelf life, considering the climatic zones.
An accelerated stability study shall be done at the following storage condition up to six months.
Temperature:
40 ± 2ºC
Relative
Humidity: 75 ± 5%
5.3.3 Storage period for stability studies can be extended after shelf life, which
shall be addressed in a specific protocol(s).
Initial
optimization and three validation batches and subsequently a minimum of one
batch (preferably the first batch of the year) per year shall be subjected to
stability studies (“Initially” means the product is subjected for stability for
the first time at the location).
Products
for initial stability studies shall be subjected to long-term and/or
Intermediate and accelerated stability studies, depending upon the market
(Zone Wise) for which the product is manufactured.
5.3.6 Products for subsequent ongoing stability studies shall be subjected to long-term stability studies, depending upon the market (Zone Wise) in which the
product is manufactured.
5.3.7 Quality Assurance department shall ensure that these samples are packed in
simulated market packing.
5.3.8 Sample quantity shall be sufficient to carry out repeat analysis as per the scheduled frequencies at different storage conditions.
5.3.9 A sampling schedule is prepared and fresh samples shall be included as and when
required.
5.3.10
The samples shall be analyzed for the different parameters as per the
guidelines given in the protocol (product specific).
5.3.11
In the case of long-term stability studies, the sample shall be analyzed 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.
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 (if applicable).
In
the case of accelerated stability studies, samples shall be analyzed at an
interval of 01, 03 months, and 6 months.
The
stability studies shall be discontinued if there shall be any loss of 5% of its
initial value of chemical purity and potency/efficacy/safety of the product as
observed after analysis and reviewing the analytical results, by a technical
committee, below the acceptance criteria as per the respective specification.
ADDITIONAL NEED-BASED STABILITY STUDIES
Accelerated stability testing
Additional
stability studies under stress conditions shall be done (if required) to check
the stability of the drug products.
The
following conditions are suggested for stress testing of drug products:
5.4.1.2.1 Increments
of 5°C or 10°C higher than an accelerated temperature of 40°C to cover the
studies of the influence of dry heat on drug products. This test is to simulate
hot conditions faced by drug products during transportation and shipment.
5.4.1.2.2 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 drug products.
5.4.1.2.3 Any
other storage conditions specified by regulatory authorities or any tie-up
companies. 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. The stress testing shall be conducted at the
time interval of 1 month, 2 months, and 3 months.
Additional
stability studies shall be done in case (but not limited) of major deviation in
process, new equipment, 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 be 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 Assurance
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 the “Change Control Committee”.
5.4.6 Additional stability studies shall be carried out as per the requirement of Tie
Up Company or the 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 one optimization and three validation batches and
subsequently a minimum of 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 Quality Assurance department shall inform the warehouse in charge of the
stability plan with product name, batch number, and sample quantity. IPQA
personnel shall collect the stability sample from a warehouse.
5.5.3 Quality
Control department/ Analytical division shall label the stability samples
individually with colored labels specified as per SOP Labeling Policy.
Quality
Control department/ Analytical division shall put the samples at different
storage conditions in stability chambers and maintain the storage record on the SOP
Finished Product Stability Sample Storage Record (Appendix).
Withdraw the samples as per the schedule and maintain the
record on APL/CQA/SOP-016/FR-02
Accelerated Stability Withdrawal Record (Appendix) and SOP Long Term Stability
Withdrawal Record (Appendix).
Bracketing of product
In
case the product has an identical formulation but there are different packing
configurations with the same primary packing material, then anyone type of
packing configuration shall be chosen and samples shall be collected.
If a product is manufactured under different brand names but the formulation, strength, and manufacturing process remain the same with the same primary packing materials then samples of anyone brand name shall be collected.
DOCUMENTATION
Maintain
the record for storage and withdrawal of finished product stability samples as
per the respective appendix.
A
monthly schedule shall be prepared on Annexure-II and send a copy of the same
to the Quality control - Head.
Send
the information to the Quality control department/ Analytical division 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.
A
calendar for stability study shall be prepared by the Quality Control
department/ Analytical division for the products undergoing stability studies.
A
stability study protocol shall be prepared and studies shall be executed
accordingly.
A
logbook for receiving and issuance of stability samples shall be maintained by
the quality control department.
The
raw data of analytical studies of stability products shall be recorded in the
test protocol.
GENERAL INSTRUCTIONS
Analytical
reports and supporting data like chromatograms/charts/graphs, etc. shall be
cross-checked by the Quality control department / analytical division for the
correctness of results, calculations, formulae used for calculating results,
analytical findings, and observations and shall be countersigned.
Unusual
observations shall be highlighted in the report and shall be informed to Tie Up
Company and/or Regulatory agency with necessary details.
Composite
data shall be prepared at the time of submission as per the requirement of that
company.
