INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL
`REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN
`USE
`
`ICH HARMONISED TRIPARTITE GUIDELINE
`
`STABILITY TESTING OF
`NEW DRUG SUBSTANCES AND PRODUCTS
`Q1A(R2)
`
`Current Step 4 version
`dated 6 February 2003
`
`
`
`
`
`
`
`
`
`This Guideline has been developed by the appropriate ICH Expert Working Group and
`has been subject to consultation by the regulatory parties, in accordance with the ICH
`Process. At Step 4 of the Process the final draft is recommended for adoption to the
`regulatory bodies of the European Union, Japan and USA.
`
`
`
`
`
`
`SENJU EXHIBIT 2290
`LUPIN v. SENJU
`IPR2015-01100
`
`Page 1 of 24
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`

`
`Q1A(R2)
`Document History
`
`
`
`
`
`First
`Codification
`
`History
`
`Date
`
`Approval by the Steering Committee under Step 2
`and release for public consultation.
`
`Approval by the Steering Committee under Step 4
`and recommendation for adoption to the three
`ICH regulatory bodies.
`Q1 was renamed Q1A.
`Approval by the Steering Committee of the first
`revision under Step 2 and release for public
`consultation.
`Approval by the Steering Committee of the first
`revision under Step 4 and recommendation for
`adoption to the three ICH regulatory bodies.
`Current Step 4 version
`Approval by the Steering Committee of the second
`revision directly under Step 4 without further
`public consultation, to include consequences of the
`adoption of Q1F (Stability Data Package for
`Registration Applications in Climatic Zones III and
`IV), and recommendation for adoption to the three
`ICH regulatory bodies.
`
`Q1
`
`Q1A
`
`Q1A(R)
`
`Q1A(R)
`
`Q1A(R2)
`
`
`
`
`
`New
`Codification
`November
`2005
`Q1
`
`Q1A
`
`Q1A(R1)
`
`Q1A(R1)
`
`16
`September
`1992
`27 October
`1993
`
`7 October
`1999
`
`8
`November
`2000
`
`6 February
`2003
`
`Q1A(R2)
`
`Page 2 of 24
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`

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`
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`COVER NOTE FOR REVISION OF Q1A(R)
`STABILITY TESTING OF
`NEW DRUG SUBSTANCES AND PRODUCTS
`
`The purpose of this note is to outline the changes made in Q1A(R) that result from
`adoption of ICH Q1F “Stability Data Package for Registration Applications in
`Climatic Zones III and IV”. These changes are:
`
`
`1. The intermediate storage condition has been changed from 30°C ± 2°C/60%
`RH ± 5% RH to 30°C ± 2°C/65% RH ± 5% RH in the following sections:
`2.1.7.1 Drug Substance - Storage Conditions - General Case
`•
`2.2.7.1 Drug Product - Storage Conditions - General Case
`•
`2.2.7.3 Drug products packaged in semi-permeable containers
`•
`3
`Glossary - “Intermediate testing”
`•
`
`
`2. 30°C ± 2°C/65% RH ± 5% RH can be a suitable alternative long-term storage
`condition to 25°C ± 2°C/60% RH ± 5% in the following sections:
`2.1.7.1 Drug Substance - Storage Conditions - General Case
`•
`2.2.7.1 Drug Product - Storage Conditions - General Case
`•
`
`
`3. 30°C ± 2°C/35% RH ± 5% RH has been added as a suitable alternative long-
`term storage condition to 25°C ± 2°C/40% RH ± 5% and the corresponding
`example for the ratio of water-loss rates has been included in the following
`section:
`2.2.7.3 Drug products packaged in semi-permeable containers
`•
`
`Mid-stream switch of the intermediate storage condition from 30°C ± 2°C/60% RH ±
`5% RH to 30°C ± 2°C/65% RH ± 5% RH can be appropriate provided that the
`respective storage conditions and the date of the switch are clearly documented and
`stated in the registration application.
`
`It is recommended that registration applications contain data from complete studies
`at the intermediate storage condition 30°C ± 2°C/65% RH ± 5% RH, if applicable, by
`three years after the date of publication of this revised guideline in the respective ICH
`tripartite region.
`
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`Page 3 of 24
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`Page 4 of 24
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`Page 4 of 24
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`STABILITY TESTING OF
`NEW DRUG SUBSTANCES AND PRODUCTS
`ICH Harmonised Tripartite Guideline
`First Recommended for Adoption at Step 4 of the ICH Process on 27 October 1993.
`Revised under Step 2 of the ICH Process on 7 October 1999 and Recommended for
`Adoption at Step 4 of the ICH Process on 8 November 2000.
`This guideline has been Revised a second time and has reached Step 4 of the ICH
`Process at the ICH Steering Committee meeting on 6 February 2003. It is
`recommended for adoption to the three regulatory parties to ICH
`
`
`
`TABLE OF CONTENTS
`1. INTRODUCTION..................................................................................................... 1
`1.1. Objectives of the Guideline........................................................................................ 1
`1.2. Scope of the Guideline................................................................................................ 1
`1.3. General Principles...................................................................................................... 1
`2. GUIDELINES
`....................................................................................................... 1
`2.1. Drug Substance
`....................................................................................................... 1
`2.1.1. General
`....................................................................................................... 1
`2.1.2. Stress Testing ................................................................................................. 1
`2.1.3. Selection of Batches........................................................................................ 2
`2.1.4. Container Closure System ............................................................................. 2
`2.1.5. Specification.................................................................................................... 2
`2.1.6. Testing Frequency .......................................................................................... 3
`2.1.7. Storage Conditions ......................................................................................... 3
`2.1.8. Stability Commitment.................................................................................... 5
`2.1.9. Evaluation ....................................................................................................... 5
`2.1.10. Statements/Labeling ...................................................................................... 6
`
`i
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`Page 5 of 24
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`Stability Testing of New Drug Substances and Products
`
`
`
`.......................................................................................................6
`2.2. Drug Product
`.......................................................................................................6
`2.2.1. General
`2.2.2. Photostability Testing.....................................................................................6
`2.2.3. Selection of Batches ........................................................................................6
`2.2.4. Container Closure System ..............................................................................7
`2.2.5. Specification.....................................................................................................7
`2.2.6. Testing Frequency...........................................................................................7
`2.2.7. Storage Conditions ..........................................................................................8
`2.2.8. Stability Commitment...................................................................................12
`2.2.9. Evaluation .....................................................................................................12
`2.2.10. Statements/Labeling .....................................................................................13
`3. GLOSSARY
`.....................................................................................................13
`4. REFERENCES
`.....................................................................................................17
`
`ii
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`Page 6 of 24
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`STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
`INTRODUCTION
`1.
`Objectives of the Guideline
`1.1.
`The following guideline is a revised version of the ICH Q1A guideline and defines the
`stability data package for a new drug substance or drug product that is sufficient for a
`registration application within the three regions of the EC, Japan, and the United
`States. It does not seek necessarily to cover the testing for registration in or export to
`other areas of the world.
`The guideline seeks to exemplify the core stability data package for new drug
`substances and products, but leaves sufficient flexibility to encompass the variety of
`different practical situations that may be encountered due to specific scientific
`considerations and characteristics of the materials being evaluated. Alternative
`approaches can be used when there are scientifically justifiable reasons.
`
`Scope of the Guideline
`1.2.
`The guideline addresses the information to be submitted in registration applications
`for new molecular entities and associated drug products. This guideline does not
`currently seek to cover the information to be submitted for abbreviated or abridged
`applications, variations, clinical trial applications, etc.
`Specific details of the sampling and testing for particular dosage forms in their
`proposed container closures are not covered in this guideline.
`Further guidance on new dosage forms and on biotechnological/biological products can
`be found in ICH guidelines Q1C and Q5C, respectively.
`
`General Principles
`1.3.
`The purpose of stability testing is to provide evidence on how the quality of a drug
`substance or drug product varies with time under the influence of a variety of
`environmental factors such as temperature, humidity, and light, and to establish a re-
`test period for the drug substance or a shelf life for the drug product and
`recommended storage conditions.
`The choice of test conditions defined in this guideline is based on an analysis of the
`effects of climatic conditions in the three regions of the EC, Japan and the United
`States. The mean kinetic temperature in any part of the world can be derived from
`climatic data, and the world can be divided into four climatic zones, I-IV. This
`guideline addresses climatic zones I and II. The principle has been established that
`stability information generated in any one of the three regions of the EC, Japan and
`the United States would be mutually acceptable to the other two regions, provided the
`information is consistent with this guideline and the labeling is in accord with
`national/regional requirements.
`
`GUIDELINES
`2.
`Drug Substance
`2.1.
`2.1.1. General
`Information on the stability of the drug substance is an integral part of the systematic
`approach to stability evaluation.
`
`2.1.2. Stress Testing
`
`1
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`Page 7 of 24
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`Stability Testing of New Drug Substances and Products
`
`Stress testing of the drug substance can help identify the likely degradation products,
`which can in turn help establish the degradation pathways and the intrinsic stability
`of the molecule and validate the stability indicating power of the analytical
`procedures used. The nature of the stress testing will depend on the individual drug
`substance and the type of drug product involved.
`Stress testing is likely to be carried out on a single batch of the drug substance. It
`should include the effect of temperatures (in 10°C increments (e.g., 50°C, 60°C, etc.)
`above that for accelerated testing), humidity (e.g., 75% RH or greater) where
`appropriate, oxidation, and photolysis on the drug substance. The testing should also
`evaluate the susceptibility of the drug substance to hydrolysis across a wide range of
`pH values when in solution or suspension. Photostability testing should be an
`integral part of stress testing. The standard conditions for photostability testing are
`described in ICH Q1B.
`Examining degradation products under stress conditions is useful in establishing
`degradation pathways and developing and validating suitable analytical procedures.
`However, it may not be necessary to examine specifically for certain degradation
`products if it has been demonstrated that they are not formed under accelerated or
`long term storage conditions.
`Results from these studies will form an integral part of the information provided to
`regulatory authorities.
`
`2.1.3. Selection of Batches
`Data from formal stability studies should be provided on at least three primary
`batches of the drug substance. The batches should be manufactured to a minimum of
`pilot scale by the same synthetic route as, and using a method of manufacture and
`procedure that simulates the final process to be used for, production batches. The
`overall quality of the batches of drug substance placed on formal stability studies
`should be representative of the quality of the material to be made on a production
`scale.
`Other supporting data can be provided.
`
`2.1.4. Container Closure System
`The stability studies should be conducted on the drug substance packaged in a
`container closure system that is the same as or simulates the packaging proposed for
`storage and distribution.
`
`2.1.5. Specification
`Specification, which is a list of tests, reference to analytical procedures, and proposed
`acceptance criteria, is addressed in ICH Q6A and Q6B. In addition, specification for
`degradation products in a drug substance is discussed in Q3A.
`Stability studies should include testing of those attributes of the drug substance that
`are susceptible to change during storage and are likely to influence quality, safety,
`and/or efficacy. The testing should cover, as appropriate, the physical, chemical,
`biological, and microbiological attributes. Validated stability-indicating analytical
`procedures should be applied. Whether and to what extent replication should be
`performed will depend on the results from validation studies.
`
`2
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`Page 8 of 24
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`Stability Testing of New Drug Substances and Products
`
`2.1.6. Testing Frequency
`For long term studies, frequency of testing should be sufficient to establish the
`stability profile of the drug substance. For drug substances with a proposed re-test
`period of at least 12 months, the frequency of testing at the long term storage
`condition should normally be every 3 months over the first year, every 6 months over
`the second year, and annually thereafter through the proposed re-test period.
`At the accelerated storage condition, a minimum of three time points, including the
`initial and final time points (e.g., 0, 3, and 6 months), from a 6-month study is
`recommended. Where an expectation (based on development experience) exists that
`results from accelerated studies are likely to approach significant change criteria,
`increased testing should be conducted either by adding samples at the final time point
`or by including a fourth time point in the study design.
`When testing at the intermediate storage condition is called for as a result of
`significant change at the accelerated storage condition, a minimum of four time
`points, including the initial and final time points (e.g., 0, 6, 9, 12 months), from a 12-
`month study is recommended.
`
`2.1.7. Storage Conditions
`In general, a drug substance should be evaluated under storage conditions (with
`appropriate tolerances) that test its thermal stability and, if applicable, its sensitivity
`to moisture. The storage conditions and the lengths of studies chosen should be
`sufficient to cover storage, shipment, and subsequent use.
`The long term testing should cover a minimum of 12 months’ duration on at least
`three primary batches at the time of submission and should be continued for a period
`of time sufficient to cover the proposed re-test period. Additional data accumulated
`during the assessment period of the registration application should be submitted to
`the authorities if requested. Data from the accelerated storage condition and, if
`appropriate, from the intermediate storage condition can be used to evaluate the
`effect of short term excursions outside the label storage conditions (such as might
`occur during shipping).
`Long term, accelerated, and, where appropriate, intermediate storage conditions for
`drug substances are detailed in the sections below. The general case applies if the
`drug substance is not specifically covered by a subsequent section. Alternative
`storage conditions can be used if justified.
`2.1.7.1. General case
`
`Study
`
`Storage condition
`
`Minimum time period covered by
`data at submission
`
`Long term*
`
`25°C ± 2°C/60% RH ± 5% RH
`or
`30°C ± 2°C/65% RH ± 5% RH
`
`12 months
`
`Intermediate** 30°C ± 2°C/65% RH ± 5% RH
`
`6 months
`
`6 months
`40°C ± 2°C/75% RH ± 5% RH
`Accelerated
`*It is up to the applicant to decide whether long term stability studies are performed
`at 25 ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH.
`
`3
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`Stability Testing of New Drug Substances and Products
`
`**If 30°C ± 2°C/65% RH ± 5% RH is the long-term condition, there is no intermediate
`condition.
`
`If long-term studies are conducted at 25°C ± 2°C/60% RH ± 5% RH and “significant
`change” occurs at any time during 6 months’ testing at the accelerated storage
`condition, additional testing at the intermediate storage condition should be
`conducted and evaluated against significant change criteria. Testing at the
`intermediate storage condition should include all tests, unless otherwise justified. The
`initial application should include a minimum of 6 months’ data from a 12-month
`study at the intermediate storage condition.
`“Significant change” for a drug substance is defined as failure to meet its specification.
`2.1.7.2. Drug substances intended for storage in a refrigerator
`
`Study
`
`Storage condition
`
`Minimum time period covered by
`data at submission
`
`Long term
`
`5°C ± 3°C
`
`12 months
`
`6 months
`
`25°C ± 2°C/60% RH ± 5% RH
`
`Accelerated
`
`Data from refrigerated storage should be assessed according to the evaluation section
`of this guideline, except where explicitly noted below.
`If significant change occurs between 3 and 6 months’ testing at the accelerated
`storage condition, the proposed re-test period should be based on the real time data
`available at the long term storage condition.
`If significant change occurs within the first 3 months’ testing at the accelerated
`storage condition, a discussion should be provided to address the effect of short term
`excursions outside the label storage condition, e.g., during shipping or handling. This
`discussion can be supported, if appropriate, by further testing on a single batch of the
`drug substance for a period shorter than 3 months but with more frequent testing
`than usual. It is considered unnecessary to continue to test a drug substance through
`6 months when a significant change has occurred within the first 3 months.
`2.1.7.3. Drug substances intended for storage in a freezer
`
`Study
`
`Storage condition
`
`Minimum time period covered by
`data at submission
`
`12 months
`
`- 20°C ± 5°C
`
`Long term
`
`For drug substances intended for storage in a freezer, the re-test period should be
`based on the real time data obtained at the long term storage condition. In the
`absence of an accelerated storage condition for drug substances intended to be stored
`in a freezer, testing on a single batch at an elevated temperature (e.g., 5°C ± 3°C or
`25°C ± 2°C) for an appropriate time period should be conducted to address the effect of
`short term excursions outside the proposed label storage condition, e.g., during
`shipping or handling.
`2.1.7.4. Drug substances intended for storage below -20°C
`4
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`
`Drug substances intended for storage below -20°C should be treated on a case-by-case
`basis.
`
`Stability Testing of New Drug Substances and Products
`
`2.1.8. Stability Commitment
`When available long term stability data on primary batches do not cover the proposed
`re-test period granted at the time of approval, a commitment should be made to
`continue the stability studies post approval in order to firmly establish the re-test
`period.
`Where the submission includes long term stability data on three production batches
`covering the proposed re-test period, a post approval commitment is considered
`unnecessary. Otherwise, one of the following commitments should be made:
`If the submission includes data from stability studies on at least three production
`1.
`batches, a commitment should be made to continue these studies through the
`proposed re-test period.
`If the submission includes data from stability studies on fewer than three
`production batches, a commitment should be made to continue these studies
`through the proposed re-test period and to place additional production batches, to
`a total of at least three, on long term stability studies through the proposed re-
`test period.
`If the submission does not include stability data on production batches, a
`commitment should be made to place the first three production batches on long
`term stability studies through the proposed re-test period.
`The stability protocol used for long term studies for the stability commitment should
`be the same as that for the primary batches, unless otherwise scientifically justified.
`
`3.
`
`2.
`
`2.1.9. Evaluation
`The purpose of the stability study is to establish, based on testing a minimum of three
`batches of the drug substance and evaluating the stability information (including, as
`appropriate, results of the physical, chemical, biological, and microbiological tests), a
`re-test period applicable to all future batches of the drug substance manufactured
`under similar circumstances. The degree of variability of individual batches affects
`the confidence that a future production batch will remain within specification
`throughout the assigned re-test period.
`The data may show so little degradation and so little variability that it is apparent
`from looking at the data that the requested re-test period will be granted. Under these
`circumstances, it is normally unnecessary to go through the formal statistical
`analysis; providing a justification for the omission should be sufficient.
`An approach for analyzing the data on a quantitative attribute that is expected to
`change with time is to determine the time at which the 95% one-sided confidence limit
`for the mean curve intersects the acceptance criterion. If analysis shows that the
`batch-to-batch variability is small, it is advantageous to combine the data into one
`overall estimate. This can be done by first applying appropriate statistical tests (e.g.,
`p values for level of significance of rejection of more than 0.25) to the slopes of the
`regression lines and zero time intercepts for the individual batches. If it is
`inappropriate to combine data from several batches, the overall re-test period should
`be based on the minimum time a batch can be expected to remain within acceptance
`criteria.
`
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`Stability Testing of New Drug Substances and Products
`
`The nature of any degradation relationship will determine whether the data should be
`transformed for linear regression analysis. Usually the relationship can be
`represented by a linear, quadratic, or cubic function on an arithmetic or logarithmic
`scale. Statistical methods should be employed to test the goodness of fit of the data on
`all batches and combined batches (where appropriate) to the assumed degradation
`line or curve.
`Limited extrapolation of the real time data from the long term storage condition
`beyond the observed range to extend the re-test period can be undertaken at approval
`time, if justified. This justification should be based on what is known about the
`mechanism of degradation, the results of testing under accelerated conditions, the
`goodness of fit of any mathematical model, batch size, existence of supporting stability
`data, etc. However, this extrapolation assumes that the same degradation
`relationship will continue to apply beyond the observed data.
`Any evaluation should cover not only the assay, but also the levels of degradation
`products and other appropriate attributes.
`
`2.1.10. Statements/Labeling
`A storage statement should be established for the labeling in accordance with relevant
`national/regional requirements. The statement should be based on the stability
`evaluation of the drug substance. Where applicable, specific instructions should be
`provided, particularly for drug substances that cannot tolerate freezing. Terms such
`as “ambient conditions” or “room temperature” should be avoided.
`A re-test period should be derived from the stability information, and a retest date
`should be displayed on the container label if appropriate.
`
`Drug Product
`2.2.
`2.2.1. General
`The design of the formal stability studies for the drug product should be based on
`knowledge of the behavior and properties of the drug substance and from stability
`studies on the drug substance and on experience gained from clinical formulation
`studies. The likely changes on storage and the rationale for the selection of attributes
`to be tested in the formal stability studies should be stated.
`
`2.2.2. Photostability Testing
`Photostability testing should be conducted on at least one primary batch of the drug
`product if appropriate. The standard conditions for photostability testing are
`described in ICH Q1B.
`
`2.2.3. Selection of Batches
`Data from stability studies should be provided on at least three primary batches of
`the drug product. The primary batches should be of the same formulation and
`packaged in the same container closure system as proposed for marketing. The
`manufacturing process used for primary batches should simulate that to be applied to
`production batches and should provide product of the same quality and meeting the
`same specification as that intended for marketing. Two of the three batches should be
`at least pilot scale batches and the third one can be smaller, if justified. Where
`possible, batches of the drug product should be manufactured by using different
`batches of the drug substance.
`
`6
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`
`Stability Testing of New Drug Substances and Products
`
`Stability studies should be performed on each individual strength and container size
`of the drug product unless bracketing or matrixing is applied.
`Other supporting data can be provided.
`
`2.2.4. Container Closure System
`Stability testing should be conducted on the dosage form packaged in the container
`closure system proposed for marketing (including, as appropriate, any secondary
`packaging and container label). Any available studies carried out on the drug product
`outside its immediate container or in other packaging materials can form a useful
`part of the stress testing of the dosage form or can be considered as supporting
`information, respectively.
`
`2.2.5. Specification
`Specification, which is a list of tests, reference to analytical procedures, and proposed
`acceptance criteria, including the concept of different acceptance criteria for release
`and shelf life specifications, is addressed in ICH Q6A and Q6B. In addition,
`specification for degradation products in a drug product is addressed in Q3B.
`Stability studies should include testing of those attributes of the drug product that
`are susceptible to change during storage and are likely to influence quality, safety,
`and/or efficacy. The testing should cover, as appropriate, the physical, chemical,
`biological, and microbiological attributes, preservative content (e.g., antioxidant,
`antimicrobial preservative), and functionality tests (e.g., for a dose delivery system).
`Analytical procedures should be fully validated and stability indicating. Whether and
`to what extent replication should be performed will depend on the results of
`validation studies.
`Shelf life acceptance criteria should be derived from consideration of all available
`stability information. It may be appropriate to have justifiable differences between
`the shelf life and release acceptance criteria based on the stability evaluation and the
`changes observed on storage. Any differences between the release and shelf life
`acceptance criteria for antimicrobial preservative content should be supported by a
`validated correlation of chemical content and preservative effectiveness demonstrated
`during drug development on the product in its final formulation (except for
`preservative concentration) intended for marketing. A single primary stability batch
`of the drug product should be tested for antimicrobial preservative effectiveness (in
`addition to preservative content) at the proposed shelf life for verification purposes,
`regardless of whether there is a difference between the release and shelf life
`acceptance criteria for preservative content.
`
`2.2.6. Testing Frequency
`For long term studies, frequency of testing should be sufficient to establish the
`stability profile of the drug product. For products with a proposed shelf life of at least
`12 months, the frequency of testing at the long term storage condition should
`normally be every 3 months over the first year, every 6 months over the second year,
`and annually thereafter through the proposed shelf life.
`At the accelerated storage condition, a minimum of three time points, including the
`initial and final time points (e.g., 0, 3, and 6 months), from a 6-month study is
`recommended. Where an expectation (based on development experience) exists that
`results from accelerated testing are likely to approach significant change criteria,
`increased testing should be conducted either by adding samples at the final time point
`or by including a fourth time point in the study design.
`7
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`
`Stability Testing of New Drug Substances and Products
`
`When testing at the intermediate storage condition is called for as a result of
`significant change at the accelerated storage condition, a minimum of four time
`points, including the initial and final time points (e.g., 0, 6, 9, 12 months), from a 12-
`month study is recommended.
`Reduced designs, i.e., matrixing or bracketing, where the testing frequency is reduced
`or certain factor combinations are not tested at all, can be applied, if justified.
`
`2.2.7. Storage Conditions
`In general, a drug product should be evaluated under storage conditions (with
`appropriate tolerances) that test its thermal stability and, if applicable, its sensitivity
`to moisture or potential for solvent loss. The storage conditions and the lengths of
`studies chosen should be sufficient to cover storage, shipment, and subsequent use.
`Stability testing of the drug product after constitution or dilution, if applicable, should
`be conducted to provide information for the labeling on the preparation, storage
`condition, and in-use period of the constituted or diluted product. This testing should
`be performed on the constituted or diluted product through the proposed in-use period
`on primary batches as part of the formal stability studies at initial and final time
`points and, if full shelf life long term data will not be available before submission, at
`12 months or the last time point for which data will be available. In general, this
`testing need not be repeated on commitment batches.
`The long term testing should cover a minimum of 12 months’ duration on at least
`three primary batches at the time of submission and should be continued for a period
`of time sufficient to cover the proposed shelf life. Additional data accumulated during
`the assessment period of the registration application should be submitted to the
`authorities if requested. Data from the accelerated storage condition and, if
`appropriate, from the intermediate storage condition can be used to evaluate the
`effect of short term excursions outside the label storage conditions (such as might
`occur during shipping).
`Long term, accelerated, and, where appropriate, intermediate storage conditions for
`drug products are detailed in the sections below. The general case applies if the drug
`product is not specifically covered by a subsequent section. Alternative storage
`conditions can be used, if justified.
`2.2.7.1. General case
`
`Study
`
`Storage condition
`
`Minimum time period
`covered by data at
`submission
`
`Long term*
`
`25°C ± 2°C/60% RH ± 5% RH
`or
`30°C ± 2°C/65% RH ± 5% RH
`
`12 months
`
`Intermediate** 30°C ± 2°C/65% RH ± 5% RH
`
`6 months
`
`6 months
`40°C ± 2°C/75% RH ± 5% RH
`Accelerated
`*It is up to the applicant to decide whether long term stability studies are performed
`at 25 ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH.
`**If 30°C ± 2°C/65% RH ± 5% RH is the long-term condition, there is no intermediate
`condition.
`
`8
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`Page 14 of 24
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