STABILITY STUDY – Welcome to

1.	Purpose:	To define the procedure for stability studies.

2.	Scope:	This guideline is applicable to the stability studies carried out for, Drug product, Drug substances and Intermediate of drug substance.

3.	References & Attachments:

	3.1	References:
		3.1.1	ICH Q1A (R2): Stability Testing of New Drug Substances and Products.
		3.1.2	ICH Q1F: Stability Data Package for Registration Applications in Climatic Zones III and IV
		3.1.3	WHO Technical Report Series, No. 863, Annex 5.


	3.2	Attachments:
		3.2.1	Attachment – 1	Format for stability sampling (routine & non routine) register.
			Attachment – 2	Format for stability test request.
			Attachment – 3	Examples of dosage forms & tests to be performed for drug product & drug substance.
			Attachment – 4	Stability study schedule & cycle.
			Attachment – 5	Format for master stability schedule.
			Attachment – 6	Format for stability sample label.
			Attachment – 7	Format for monthly stability schedule.
			Attachment – 8	Format for stability protocol issuance register.
			Attachment – 9	Format for ACC/long term stability summary report.
			Attachment – 10	Format for stability discontinuation authorization.
			Attachment – 11	Format for master stability schedule (computerized).
			Attachment – 12	Format for stability sample reconciliation & destruction.

4. Responsibilities:

	4.1	Corporate Quality:
		4.1.1	To review stability data received from locations.
		4.1.2	To provide suggestions to location QC incase of stability failures.

4.2	Quality Assurance:
	4.2.1	To prepare stability schedule.
	4.2.2	To approve the stability protocol.
	4.2.3	To withdraw the stability samples.
	4.2.4	To send the samples to QC along with stability test request.
	4.2.5	To maintain the related documents.

4.3	Quality Control:

	4.3.1	Stability coordinator (QC chemist):
		4.3.1.1	To receive, schedule, incubate & analyze the stability samples.
		4.3.1.2	To inform stability failure results to QC head, if any.
		4.3.1.3	To prepare & update the stability summary report.
		4.3.1.4	To maintain stability documents along with raw data.

	4.3.2	Head QC:
		4.3.2.1	To monitor the stability program.
		4.3.2.2	To approve the stability protocol.
		4.3.2.3	To issue the stability protocol.
		4.3.2.4	To initiate investigation incase of out of specification (OOS) results.
		4.3.2.5	To authorize deviation if any.
		4.3.2.6	To authorize stability discontinuation if any.
		4.3.2.7	To approve the stability summary report.
		4.3.2.8	To inform about stability failure to head quality, location & regulatory.
		4.3.2.9	To take necessary actions incase of significant change or failure.

4.4	Head Quality, Head location & regulatory:
	4.4.1	To approve the stability protocol.
	4.4.2	To provide suggestions incase of stability failures or significant changes.

NOTE : RESPONSIBILITY MATRIX SHALL BE CHANGED AS PER THE EXISTING ORGANGRAM OF THE LOCATION.

5. Definition of terms:

	5.1	Stability:
		The term with respect to a drug dosage form refers to the chemical & physical integrity of the dosage unit & when appropriate, the ability of the dosage unit to maintain protection against microbial contamination.

	5.2	ICH:
		The International Conference on Harmonization.

	5.3	Significant change for drug product:
		5.3.1	A 5 percent change in assay from its initial value, or failure to meet the acceptance criteria for potency when using biological or immunological procedures.
		5.3.2	Any degradation product’s exceeding its acceptance criterion.
		5.3.3	Failure to meet acceptance criteria for appearance, physical attributes and functionality test (e.g. color, phase separation, resuspendibility, caking, hardness, dose delivery per actuation). However, some changes in physical attributes (e.g., softening of suppositories, melting of creams) may be expected under accelerated conditions.
		5.3.4	Failure to meet the acceptance criterion for pH.
		5.3.5	Failure to meet the acceptance criteria for dissolution for 12 dosage units (USP stage 2).

	5.4	Significant change for drug substance:
		5.4.1	Significant change for a drug substance is defined as failure to meet its specification.
	5.5	Intermediate / Intermediate stage material:
		5.5.1	A material produced during API processing that undergoes further molecular change or purification before it becomes the API.

General information:

6.1

Purpose of Stability Study:

The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with the time under influence of a variety of environmental factors such as temperature, humidity and light, air & to establish a retest period for the drug substance or a shelf life for the drug product & recommended storage conditions.

6.2

Climatic Zones:

The four worldwide climatic Zones recognized by ICH are based on observed temperature & relative humidity, both outside and inside rooms, from which mean temperatures and average humidity values are calculated. Following are the four climatic zones.

Zone No.	Zone ID	Areas covered under the zone
Zone –I	Temperate (200 C, 42% RH)	United Kingdom, Northern Europe, Canada, Russia, United states, Japan
Zone –II	Mediterranean or subtropical (21.60 C, 52% RH)	United States, Japan, Southern Europe (Portugal-Greece).
Zone –III	Hot and Dry (26.40 C, 35% RH)	Australia, Argentina, Egypt, Iran, Iraq, Sudan, India
Zone –IV	Hot and Humid (26.70 C, 76% RH)	Brazil, Ghana, Indonesia, Nicaragua, Philippines, India.

6.3

Factors affecting stability of the product:

6.3.1

Improper storage condition like,

Temperature:

The rate of chemical reaction increases exponentially for each 10°C-increase in temperature.
This relationship has been observed for nearly all drug hydrolysis and some drug oxidation reaction.
Refrigeration may cause extreme viscosity in some liquid drugs and cause super saturation in others.

Freezing may either break or cause a large increase in the droplet size of emulsions, it can denature proteins & in rare cases it can cause less soluble polymorphic states of some drugs to form some dissolved carboxylic acid loses carbon dioxide from the carboxyl group when heated. The resulting product has reduced pharmacological potency.

Light:

Exposure to primarily, UV illumination may cause oxidation (photo- oxidation) and scission (Photolysis) of covalent bonds.

Air:

Presence of oxygen, nitrogen.

Humidity (Moisture):

Esters & beta-lactoms are the chemical bonds that are most likely to hydrolyze in the presence of water. e.g. the acetyl ester in aspirin is hydrolyzed to acetic acid and salicylic acid in the presence of moisture, but in a dry environment the hydrolysis of aspirin is negligible.

6.3.2

Change in formulation.

6.3.3

Change in primary pkg. material.

6.3.4

Change in batch size.

6.3.5

Change in process or critical process parameters.

6.3.6

Change in critical mfg. equipment.

6.3.7

Change in vendor of API and/or critical raw material

6.4

Criteria for acceptable level of stability:

NATURE OF STABILITY	CONDITIONS REQUIRED TO BE MAINTAINED THROUGH OUT THE SHELF LIFE OF DRUG PRODUCT
Chemical	Each active ingredient retains its chemical integrity and labeled potency within specified limits.
Physical	The original physical properties including appearance, uniformity, dissolution etc. are retained.
Microbiological	Sterility or resistance to microbial growth is retained according to the specified requirement. Antimicrobial agents that are present retain effectiveness within the specified limit.
Toxicological	No significant increase in toxicity occurs.

Note: Where, “Significant change/ failure” occurs due to accelerated testing during six months, additional testing at an intermediate condition should be conducted.

6.5

Types of stability studies:

@Note : If 30 + 2° C at 65 + 5 % RH is the long-term condition, there is no intermediate condition.

For products to be exported in zone I & II countries, long term stability condition shall

be, 25°C + 2°C & 60% + 5% RH.

For products to be exported in zone III & IV countries, long-term stability condition shall be 30 + 2° C at 65 + 5 % RH.
For products to be exported in zone I /II and III/IV (in combination of I/II & III/IV)long term stability condition shall be 30 + 2° C at 65 + 5 % RH.
Intermediates stage materials stability shall be done at ambient temperature.

Procedure:

7.1

Criteria for deciding type of stability study to be performed:

7.1.1

Routine stability study:

7.1.1.1

In case of routine stability, samples of one batch per product per year shall be kept for long-term stability study.

7.1.2

Non routine stability study:

Following are the examples of non-routine stability study.

7.1.2.1

Incase of new product after successful scale-up (i.e. only qty. adjustment or process adjustment is permitted during scale-up), samples of three consecutive batches/validation batches shall be kept for ACC & long-term stability.

7.1.2.2

Incase of drug product manufacturing; hold time/stability study at intermediate stage shall be performed while manufacturing of exhibit batch or process validation batch.

E.g. Hold time study of,

* Blend/lubricated material.

* Compressed tablets (Uncoated tablets)/Coated tablets.

* Unfiltered / Filtered bulk.

7.1.2.3

Incase of drug substance manufacturing; hold time/stability study of intermediate stage material shall be performed.

7.1.2.4

Three consecutive batches means: Three batches of a product X manufactured can have batch numbers X-001, X-005 & X-007, where, in-between batch numbers can be of any other product

7.1.2.5

Stability studies shall be performed on each individual strength and container/pack size of the drug product unless bracketing or matrixing is applied. i.e. If the product is packed in three different size (100 count, 500 count & 1000 count) of container/bottle/jar, stability study for all three pack size shall be done.

7.1.2.6

Stability study of evaluation batch means, recovery added batch, reprocessed batch, recommendation in temporary or permanent change control or incidence report etc.

7.1.2.7

In case if the scale up is not successful or major changes done, 3M ACC or ACC & CRT stability or stability study as per recommendation in temporary or permanent change shall be done.

7.1.2.8

Photostability studies shall be done as per regulatory requirement of respective country and/or labeling statement.

7.2

Sampling for stability studies:

7.2.1

QA shall inform QC regarding type of stability study to be performed.

7.2.2

QC shall calculate the sample quantity and shall inform to QA.

7.2.3

Total sample quantity per batch shall be 1.5 times the quantity required for single complete or partial analysis & based on number of stations plus additional two stations (since stability testing has to be continued for 12 month beyond the expiry).

7.2.4

In case of drug products (formulation), QA shall withdraw random samples through out packaging of the batch (to have representative samples of the entire batch) after verifying according to in process checks & FP results within limit & in the final pack so as to simulate the market pack.

7.2.5

In case of drug substance (API), QA shall withdraw stability samples at the time of finished product sampling and pack in such a way so as to simulate market pack and shall ensure the FP results within limit before incubation of the samples.

7.2.6

After withdrawal of the samples, QA shall enter the details like, sr. no., product name, batch no., date of sample withdrawal shall be mentioned in stability (routine & non routine) sampling register (Attachment – 1).

7.2.7

QA shall mention qty. of sample, sampled by & date & purpose, in batch manufacturing document.

7.2.8

QA shall enter the details like, Sr. no., product name, batch no., manufacturing date, expiry date, storage condition, purpose, stability condition, test request for, sampled by & date, sample qty., in the “stability test request form” (Attachment – 2) in duplicate & send samples to QC.

7.3

Preparation of stability protocol

7.3.1

Stability protocol of each product shall be prepared by quality control referring examples of dosage forms & tests to be performed (Attachment –3), stability study schedule & cycle (Attachment – 4).

7.3.2

Protocol shall be checked by location – QA and department head and approved by quality-head, factory-head and regulatory head.

7.4

Receipt & storage of stability samples

7.4.1

On receipt of stability samples, QC chemist shall verify the sample details against the stability test request form and shall return the form duly signed in received by and date & retain a copy of the same. (Attachment-2)

7.4.2

Details like, sr. no., sample received by & date, product, batch no., manufacturing date, expiry date, purpose of stability, stability condition, qty. of sample, shall be mentioned in the master stability schedule (Attachment – 5).

7.4.3

Sr. no., product, batch no., stability condition, stability station, ref. Page no. of master stability schedule, due date, analyzed by & date, analysis ref. Document no., checked by, remark shall be mentioned in monthly stability schedule on weekly basis(Attachment- 7).

7.4.4

Sr. no., product, batch no., mfg. date, exp. date, purpose, stability condition, shall be mentioned in computerized master stability schedule. (Attachment- 11).

7.4.5

Stability coordinator shall verify entries made in all three (master stability schedule, monthly stability schedule & computerized master stability schedule) documents.

7.4.6

Samples shall be stored as per labeled storage condition until incubation.

7.5

Incubation of stability samples:

7.5.1

Stability coordinator shall ensure that batches planned for stability study pass in all tests as per the finished product specifications.

7.5.2

Sample quantity shall be divided according to the sample required per study for accelerated and long term conditions & shall be labeled as per attachment –6.

7.5.3

Samples shall be incubated as per below guideline.

Examples Of Product (Formulation / API/ Intermediate) Storage Condition	Stability Sample Incubation Condition
	Accelerated		Long term
	Temperature	% RH	Temperature	% RH
Controlled room temperature (CRT)	40°C + 2°C	75% + 5%	30°C + 2°C or	65% + 5% or
			25°C + 2°C	60% + 5%
2°C to 8°C	25°C + 2°C	60% + 5%	2°C to 8°C	—

7.5.4

After incubation of samples, date of incubation, analysis due date at required stations with ref. Page no. of monthly stability schedule shall be mentioned in attachment -5.

7.5.5

Temp. & Humidity of stability incubator shall be monitored on daily basis.

7.5.6

If incubation of the stability samples is delayed by 30 days or more, initial (0 month) analysis shall be done again before incubation.

7.5.7

Incase if ACC stability oven is out of order, samples shall be transferred at required stability condition within 24 hrs.

7.5.8

Incase if CRT stability oven is out of order, samples shall be transferred at required stability condition within 72 hrs.

7.5.9

Incase of 2-8°C CRT condition, if the stability chamber (which may be cold room/refrigerator) is out of order, samples shall be transferred at required stability condition within 72 hrs.

7.5.10

Incase of intermediate stage material, stability shall be done only for long term condition & shall be considered valid until further change in mfg. process is done. (Applicable to API mfg. location).

7.6

Scheduling stability program:

7.6.1

Analysis for due stability stations shall be planned referring monthly stability schedule verified by head QC.

7.7

Issuance of stability protocol:

7.7.1

Head QC or designee shall arrange for the issuance of stability protocol & shall mention issuance no., product, batch no., due station, protocol no., issued on, issued by, issued to, retrieved on & remarks if any in protocol issuance register (Attachment -8).

7.8

Withdrawal of stability samples from incubators

7.8.1

Stability coordinator shall withdraw the stability samples from the incubator at the time of analysis & shall mention qty., date & initial below the due month.

7.8.2

Qty. withdrawn, withdrawn by & date shall be mentioned in the next row in the master stability schedule (Attachment – 5) at the time of sample withdrawal.

7.8.3

Stability coordinator shall also make entry of sample withdrawn in “Stability Sample Reconciliation and Destruction Form” for “Qty. Drawn”, “Qty. Drawn Date / By”, “Station No./ Due on”, “Qty. Balance”, “Remarks”. (Attachment – 12).

7.9

Analysis & preparation of report:

7.9.1

Chemist shall ensure the availability of standards of all the related substances/ degradant required for the analysis, either from the Research & Development or Pharmacopoeia l commissions.

7.9.2

If at the time of initial analysis, analytical method was not stability indicating, stability sample at next station shall be analyzed as per stability indicating method.

7.9.3

Chemist shall analyze the samples as per the test procedures given in the issued stability protocol and enter the data in the protocol during analysis.

7.9.4

Analysis of samples shall be completed within below tolerance limit from due date.

Sr. No.	Stability Station	Tolerance (From due date of analysis)
	1M , 2M, 3M ACC	+ 07 days
	3M long term	+ 07 days
	6M ACC 6M long term	+ 15 days
	9M & onwards long term.	+ 30 days

7.9.5

In case of delay in analysis, authorization in deviation form shall be taken from dept. head.

7.9.6

Chemist shall attach the chromatograms, TLC plates, UV spectra etc. with the protocol & analytical report.

7.9.7

Chemist shall ensure that actual values of the test results are reported instead of complies or confirms.

7.9.8

Chemist shall give the protocol (which includes analytical report & summary sheet) along with raw data for the cross checking to the designated person and then to the Head-QC for the approval.

7.9.9

Product name, batch no., mfg. date, exp. date, dosage form (where applicable), pack size, primary pkg. Material, storage condition, purpose of stability, test results, master protocol number shall be mentioned by the chemist in the stability summary report (Attachment – 9) which is part of stability protocol.

7.9.10

Approved document (analytical report, protocol & raw data) shall be filed in a respective product stability data file.

7.9.11

In case of delay in analysis, real time of analysis in month (nearer to start / end of the month) shall be mentioned in summary report.

e.g if 6M station was due on 05/10/05 & analysis done on 14/10/05 (i.e before 15/10/05), 7M station shall be reported.

e.g if 6M station was due on 05/10/05 & analysis done on 17/10/05 (i.e after 15/10/05), 8M station shall be reported.

7.10

Handling of OOS (out of specification)/out of trend /failure results or significant change:

7.10.1

Any out of the specification results shall be intimated to the Head-QC.

7.10.2

Head -QC shall investigate the out of specification (OOS) results according to the SOP.

7.10.3

In event of any stability failure/ significant change (Out of trend results), Head QC shall inform to location head, location quality head, , regulatory & CQ and shall suggest, (but not limited to)

In event of any out of trend results in ACC condition, additional testing at an intermediate condition i.e. 30°C ±2°C/ 65% ± 5% RH.

In event of any out of trend results in CRT condition, location shall reanalyze the samples of the batch under investigation with control sample of same age samples of other available batches or as per repeat analysis SOP.

Shall discuss with technical group comprising of Head-quality, location, regulatory, FDD & CQ, to take joint decision for recall / revision of formulation/product storage condition/packaging material.

7.10.4

In case of stability of intermediate stage material, if fails at any station, stability of material of next lot shall be studied for in-between period (between two stations). For example, if material fails at 90 days station and earlier station is 60 days, stability of next lot shall be studied in between period i.e. at 45 days.

7.11

Stability sample reconciliation & destruction:

7.11.1

After completion of stability study, stability coordinator shall reconcile the stability samples and shall make necessary entries for the destruction of the samples in “Stability Sample Reconciliation and Destruction Form” (Attachment – 12).

7.12

Handling of changes in specification or test procedure:

7.12.2

Condition 1: Specification changes but test procedure doesn’t change, If

next stability station.

Pass: Take Change control and revise the stability protocol

Fail: Trigger process change, keep stability samples with new process,

and continue old stability with old specification.

Method validation: Not required if LOD, LOQ & linearity are established

below the revised limit. Otherwise required.

7.12.2

Condition 2: Specification doesn’t change but test procedure changes, if

next stability station with validated method,

Pass: Take Change control and revise the stability protocol

Fail: Trigger process change, keep stability samples with new process,

continue old stability with old test procedure

Method validation: Required.

7.12.3

Condition 3: Specification and test procedure both change, If next

stability station with validated method,

Pass: Take Change control and revise the stability protocol

Fail: Trigger process change, keep stability samples with new process,

and continue old stability with old specification and test procedure

Method validation: Required.

7.13

Discontinuation of study:

7.13.1

In case of discontinuation of stability study, QA shall mention product, batch no, stability condition, reason for discontinuation, reference, and take authorization from quality head and send intimation to QC for the discontinuation of study.

7.13.2

Chemist shall mention remaining stability station, qty. to be destroyed, reason for destruction, destruction procedure to be followed, remarks if any & shall get authorization from Head-QC in (Attachment – 10).

7.13.3

Chemist shall destroy the remaining samples & mention qty. destroyed, date of destruction & destruction procedure in the (Attachment – 10).

7.13.4

Necessary entries shall also be made in sample reconciliation & destruction form. (Attachment –12).

	7.14		Strategy for stability, in the cases of product transfers:

			7.14.1		While product transfer, location A shall send all the samples along with stability schedule to location B.
			7.14.2		Location B will charge the stability samples and continue stability as per the location A’s schedule.
			7.14.3		The location B shall continue keeping stability of new batches (one batch per year) as per the system and scale up batch stability as per GMP norms.
			7.14.4		Further, there will be three situations in case of product registration for export purpose.
			7.14.5		Case 1: *If Product is already registered for export from location A and transferred at Location B* Manufacturing of the product shall be continued at location B, and shall be packed at location A. Testing of FP shall be at location B. COA shall be generated from location A based on location B’s results. Location A shall withdraw stability samples as per the system and send to location B. Location B shall charge the samples as per the required stability conditions and analyze as per the schedule. Re-registration shall be continued from location A and manufacturing/testing/packing/ stability system shall be continued as above.
			7.14.6		Case 2: *Export registration of new product (which is already there in domestic at location B), and if product is decided to be registered from location A.* Stability data available at location B, of domestic batches, shall be submitted. Manufacturing/testing/packing/stability system shall be continued as per case 1.
			7.14.7		Case 3: Export registration of new product (which is already there in domestic at location A and transferred to location B within the 3 month of stability program), then it is advisable to registered from location A. Stability sample along with program and raw data to submit to location B and location B shall continue stability that station onwards. Manufacturing/testing/packing/stability system shall be continued as per case 1.
8.Guideline History:
Guideline No.		Effective Date		Super-sedes		Supersedes Date	Reason For Revision
031/02R1		15.09.05		00031/02		20.11.03	To revise the format of guideline as per guideline on CQ guideline. To change the definition of significant change as per ICH-Q1A(R2). To include information about climatic zones. To revise as per ICH -Q1F guidance. To change intermediate storage condition from 30°C + 2°C & 60% + 5% to 30°C + 2°C & 65% + 5% to harmonize intermediate storage conditions for zones I & II with long term condition for zones III & IV. To provide alternative long term storage condition i.e. 30°C + 2°C & 65% + 5% to 25°C + 2°C & 60% + 5% To remove evaluation of secondary packing material from attachment –III since it was incidence based. To remove ”incase of sterile & non sterile liquid products” from Point no. 5.2.3 (sr. no. of earlier guideline) since applicable to all dosage forms & API. To provide more clarity for handling of out of specification results during stability testing. To have data for shelf life extension, depending upon the expiry period, the stability testing has to be continued for 12 months beyond the expiry. Earlier it was 6 months. To merge CQ directive no. 0013 “Strategy for stability, in the cases of product transfers” with this guideline.

Guide-line No.

Effective Date

Super-sedes

Supersedes

Date

Reason For Revision

031/02R1

15.09.05

00031/02

20.11.03

To include time points for intermediate stability condition.
Procedure clarified for routine & non routine stability.
To include “stability sample reconciliation & destruction” format & related procedure.
The therapeutic effect remains unchanged” removed from “Criteria for acceptable level of stability”since we do not monitor the same.
Included photostability & intermediate stage material (incase of API) in types of stability studies.
Stability sample analysis tolerance for 1M & 2M ACC condition changed from + 3 days to + 7 days.
In case of delay in analysis, real time of analysis in month (nearer to start / end of the month) explained with an example.
Incase of drug product, hold time study included under non routine stability.
Included that stability study of multiple packs of same strength & of individual strength of drug product shall be done unless bracketing or matrixing is applied.
Attachment -3 (Examples of dosage forms & tests to be performed) updated for API & more dosage forms like nasal spray & tests like BET, MLT, Sterility, PMT etc.
API B. No. included in stability summary report.
Attachment-I changed to make it simple.

Prepared by: Approved by:

Date: Date:

ATTACHMENT –1

Format for STABILITY SAMPLING REGISTER (ROUTINE & NON ROUTINE)- YEAR 2005

Sr. No.	Product	B. No.	Type of stability			Sample withdrawn on		Sample withdrawn by		Remarks /Reason for stability
Sr. No.	Product	B. No.	Routine	Non routine				Sample withdrawn by		Remarks /Reason for stability

ATTACHMENT-2

Format of STABILITY TEST REQUEST

FROM : QA

TO : QC

DATE :

NO. :

PRODUCT :

B.NO. :

MFG. DATE :

EXP. DATE :

STORAGE CONDITION :

TYPE OF STABILITY/PURPOSE : {Routine / Non routine (deviation/validation/

recovery/new product)}

(Give ref. Document no. incase of

non routine stability study)

STABILITY CONDITION :

TEST REQUEST FOR :

(mention name of tests incase of non routine stability)

SAMPLED BY(QA)/DATE :

SAMPLE QTY. :

SAMPLE RECEIVED BY(QC) :

DATE :

ATTACHMENT – 4

STABILITY STUDY SCHEDULE & CYCLE

Time points for Accelerated stability: 0,1,2,3 and 6 Months.

Time points for Intermediate stability: 3, 6, 9, 12 Months.

Time points for Long-term stability for formulation: 0,3,6,9,12,18,24,36,48,60, 66 & 72 Months depending upon expiry.

Depending upon the expiry period, stability testing has to be continued for 12 month beyond the expiry.

Time points for Long-term stability for API: 0,3,6,9,12,18,24,36,48,60, 66 & 72 Months.

Time points for Intermediates stage materials stability (At ambient temperature): 0,1,2,3,6,9,12 months.

ATTACHMENT – 6

Format for STABILITY SAMPLE LABEL

PRODUCT	:
B. NO.	:
STORAGE AT	:
KEPT ON	:
Qty./STATION	:

________________________________________________________________________________

ATTACHMENT – 7

Format for MONTHLY STABILITY SCHEDULE

Month : July Year: 2001

Sr. No.	Product	Batch No.	Stability Condition	Stability station	Ref. page No. of master stability schedule	Due Date	Analyzed by/Date	Analysis reference document no.	Checked by	Remark
15	ABCD	K-005	ACC (40°C / 75 % RH)	1M	01	18/7/01	MNP / 20/7/01	MNP / 032/ 01	PKN

ATTACHMENT – 8

Format for STABILITY PROTOCOL ISSUANCE REGISTER

Issuance No.	Product	Batch No.	Due Station	Protocol No.	Issued on	Issued by	Issued to	Retrieved on	Remarks

ATTACHMENT – 9

Format of ACC/LONG TERM STABILITY SUMMARY REPORT

Product name: Batch No.:

Mfg. dt.: Exp.dt.:

API lot /A. R. number:

Dosage form: Batch size:

Pack size:

Primary packaging material: Storage condition:

Purpose of the study:

Test	Specification	ACC/LONG TERM Stability station (month)
		Initial	**Month	**Month	Month	Month
		0	1	2	3	6


Protocol No.

Remarks:

Entered by: Checked by:

** 1Month & 2M stations will be applicable to only ACC condition.

ATTACHMENT – 10

Format for STABILITY DISCONTINUATION AUTHORIZATION

FROM : QUALITY ASSURANCE

TO : HEAD QUALITY CONTROL

PL. DISCONTINUE THE STABILITY STUDY OF PRODUCT & B. NO. AS MENTIONED BELOW.

PRODUCT:

BATCH NO:

STABILITY

CONDITION:

REASON FOR DISCONTINUATION:

REFERENCE:

PREPARED BY : AUTHORIZED BY : RECEIVED BY : (QA) (Head Quality) (QC)

To be filled in by QC

STABILITY STATION REMAINING:

QTY. TO BE DISTROYED:

DESTRUCTION PROCEDURE TO BE FOLLOWED:

REMARKS:

PREPARED BY

DATE

AUTHORIZED BY

(Head QC)

DATE

ATTACHMENT – 3

EXAMPLES OF DOSAGE FORMS & TESTS TO BE PERFORMED

FOR DRUG PRODUCT & DRUG SUBSTANCE

The stability evaluation parameters shall be selected from the below table but shall not be limited to the table.
Additional important parameter may be considered based on product & its dosage and any of the below tests may be excluded with scientific rational.

Drug product (Dosage Form)

Tests

Appearance

Viscosity

Odor

Dissolu-tion /Solubility

Hard-ness &/or friability

Related substances / chromatogra-phic purity

Clarity/ Colour / %T

LOD/ Water/ mois-ture

Assay (including preservative/ antioxidant)

Sterility

BET

PET

PMT

MLT

Tablet

Yes

—

Yes

—

Yes

—

Yes

Capsule

Yes

—

Yes

—

Yes

—

Yes

—

Yes

Soft gel capsule

Yes

—

Yes

—

Yes

—

Yes

—

Yes

Oral liquid/ Suspension

Yes

—

Yes

—

Yes

—

Yes

—

Yes

Cream/ ointment

Yes

—

Yes

—

Yes

—

Yes

—

Yes

Nasal sprays /Inhalers (including DPI)

Yes

—

Yes

yes

Yes

—

Yes

Injection

Yes

—

Yes

—

Yes

—

Lyophilized product

Yes

—

Yes

—

Eye drops

Yes

—

Yes

—

Yes

—

Non sterile API

Yes

—

yes

—

Yes

—

Yes

Sterile API

Yes

—

yes

—

Yes

—

Identify any unknown impurity if observed out of limit at any station.
Appearance includes coating integrity (incase of coated tablet) & brittleness incase of hard gelatin capsules, precipitation & cloudiness of content incase of soft gelatin capsules.
Metered dose inhaler should include dose content uniformity, extractable/leachable
Reconstitution time test should be done for lyophilized products.
PET : preservative efficacy test. BET : Bacterial endotoxin test. PMT : Particulate matter test. MLT: Microbiological limit test.

ATTACHMENT – 5

Format of MASTER STABILITY SCHEDULE

Sr. No.

Sample received by /Date

Product

B. No.

Mfg. Date

Exp. Date

Purpose

Stability condition

Sample Qty.

Sample incub-ated on

Rem-ark

Stability Station

432

MNP / 16/6/01

ABCD

K-005

06/01

04/03

New product

ACC (40°C/75%RH)

XY vials

18/6/01

Nil

18/7/01 / 01*

18/8/01 / 31*

18/9/01/61*

18/12/01/ 78*

Qty. withdrawn, date & initial —–🡪

10 vials/ 20/7/01 /MNP

10 vials/ 18/8/01 /MNP

10 vials/ 20/9/01 /MNP

10 vials/ 20/12/01 /MNP

are ref. Page no. of monthly stability schedule.

ATTACHMENT – 11

Format for MASTER STABILITY SCHEDULE (Computerized)

Sr. No.	Name of product	B. No.	Mfg. Date	Exp. Date	Purp-ose	Stability condi-tion	Sample kept on	Stability Station													Remarks
									1	2	3	6	9	12	18	24	36	48	60	72

ATTACHMENT – 12

STABILITY SAMPLE RECONCILIATION AND DESTRUCTION FORM

Product

B. No.

Quantity

Kept On

Quantity

Kept On

Condition

Qty. Drawn

Qty. Drawn

Station

Qty. Balance

Remarks

Qty Drawn

Qty. Drawn

Station

Qty. Balance

Remarks

Date

No.

Due on

Date

No.

Due on

Remaining Sample destroyed by: ______ Date: _____ Remaining Sample destroyed by: ________ Date: _______

Author

Administrator

"A seasoned professional with a Master's in Chemistry, the author brings more than two decades of expertise in Quality Control, Analytical Method Validation, and advanced QMS investigation. Their experience is globally validated by successful management of major regulatory audits, including those conducted by the US, EU, Brazil, and Russian authorities."

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References & Attachments:

Attachment – 1

Attachment – 2

Attachment – 3

Attachment – 4

Attachment – 5

Attachment – 6

Attachment – 7

Attachment – 8

Attachment – 9

Attachment – 10

Attachment – 11

Attachment – 12

4.1

4.1.1

4.1.2

4.2

4.2.1

4.2.2

4.2.3

4.2.4

4.2.5

4.3

4.3.1

Stability coordinator (QC chemist):

4.3.2

4.4

4.4.1

4.4.2

5.3.1

5.3.2

5.3.3

5.3.4

5.3.5

5.4.1

5.5.1

General information:

6.3.1

6.3.2

6.3.3

6.3.4

6.3.5

6.3.6

6.3.7

Procedure:

7.1.1

7.1.2

7.2.1

7.2.2

7.2.3

7.2.4

7.2.5

7.2.6

7.2.7

7.2.8

7.3

7.3.1

7.3.2

7.4

7.4.1

7.4.2

7.4.3

7.4.4

7.4.5

7.4.6

7.5

7.5.1

7.5.2

7.5.3

Examples Of Product (Formulation / API/ Intermediate)

Storage

Accelerated

Temperature

% RH

Temperature

% RH

40°C + 2°C

75% + 5%

30°C + 2°C

65% + 5%