Guidance for Industry
`Q1A(R2) Stability Testing
`of New Drug Substances
`and Products
`
`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Drug Evaluation and Research (CDER)
`Center for Biologics Evaluation and Research (CBER)
`
`November 2003
`ICH
`
`Revision 2
`
`MYLAN - EXHIBIT 1036
`
`

`

`Guidance for Industry
`Q1A(R2) Stability Testing
`of New Drug Substances
`and Products
`
`Additional copies are available from:
`
`Office of Training and Communication
`Division of Drug Information, HFD-240
`Center for Drug Evaluation and Research
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, MD 20857
`(Tel) 301-827-4573
` http://www.fda.gov/cder/guidance/index.htm
`
`or
`
`Office of Communication, Training and
`Manufacturers Assistance, HFM-40
`Center for Biologics Evaluation and Research
` Food and Drug Administration
`1401 Rockville Pike, Rockville, MD 20852-1448
` http://www.fda.gov/cber/guidelines.htm.
` (Tel) Voice Information System at 800-835-4709 or 301-827-1800
`
`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Drug Evaluation and Research (CDER)
`Center for Biologics Evaluation and Research (CBER)
`
`November 2003
`ICH
`
`Revision 2
`
`

`

`Contains Nonbinding Recommendations
`
`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION (1)........................................................................................................... 1
`A. Objectives of the Guidance (1.1)............................................................................................1
`B.
`Scope of the Guidance (1.2)...................................................................................................2
`C. General Principles (1.3).........................................................................................................2
`II. GUIDANCE (2) ..................................................................................................................... 2
`A. Drug Substance (2.1).............................................................................................................2
`
`1. General (2.1.1).......................................................................................................................2
`2. Stress Testing (2.1.2) ..............................................................................................................3
`3. Selection of Batches (2.1.3) .....................................................................................................3
`4. Container Closure System (2.1.4).............................................................................................3
`5. Specification (2.1.5)................................................................................................................3
`6. Testing Frequency (2.1.6)........................................................................................................4
`7. Storage Conditions (2.1.7) ......................................................................................................4
`8. Stability Commitment (2.1.8) ...................................................................................................6
`9. Evaluation (2.1.9)...................................................................................................................7
`B. Drug Product (2.2) ................................................................................................................8
`
`1. General (2.2.1).......................................................................................................................8
`2. Photostability Testing (2.2.2) ..................................................................................................8
`3. Selection of Batches (2.2.3) ....................................................................................................8
`4. Container Closure System (2.2.4).............................................................................................8
`5. Specification (2.2.5)................................................................................................................9
`6. Testing Frequency (2.2.6)........................................................................................................9
`7. Storage Conditions (2.2.7) ....................................................................................................10
`8. Stability Commitment (2.2.8) .................................................................................................14
`9. Evaluation (2.2.9).................................................................................................................15
`10. Statements/Labeling (2.2.10) ...............................................................................................16
`GLOSSARY (3)........................................................................................................................... 17
`REFERENCES (4) ...................................................................................................................... 21
`ATTACHMENT List Of Revision 2 Changes......................................................................... 22
`
`i
`
`

`

`Contains Nonbinding Recommendations
`
`Guidance for Industry1
`
`Q1A(R2) Stability Testing of New Drug
`Substances and Products
`
`This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It
`does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
`You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
`and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
`implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
`number listed on the title page of this guidance.
`
`I.
`
`INTRODUCTION (1) 2
`
`This guidance is the second revision of Q1A Stability Testing of New Drug Substances and
`Products, which was first published in September 1994 and revised in August 2001. The
`purpose of this revision is to harmonize the intermediate storage condition for zones I and II with
`the long-term condition for zones III and IV recommended in the ICH guidance Q1F Stability
`Data Package for Registration Applications in Climatic Zones III and IV. The changes made in
`this second revision are listed in the attachment to this guidance.
`
`A.
`
`Objectives of the Guidance (1.1)
`
`This guidance is intended to define what stability data package for a new drug substance or drug
`product is sufficient for a registration application within the three regions of the European Union
`(EU), Japan, and the United States. It does not seek to address the testing for registration in or
`export to other areas of the world. The guidance exemplifies 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.
`
`
`1 This guidance was developed within the Expert Working Group (Quality) of the International Conference on
`Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been
`subject to consultation by the regulatory parties, in accordance with the ICH process. This document was endorsed
`by the ICH Steering Committee at Step 4 of the ICH process, February 2003. At Step 4 of the process, the final draft
`is recommended for adoption to the regulatory bodies of the European Union, Japan, and the United States.
`
`2 Arabic numbers reflect the organizational breakdown in the document endorsed by the ICH Steering Committee
`at Step 4 of the ICH process.
`
`1
`
`

`

`Contains Nonbinding Recommendations
`
`B.
`
`Scope of the Guidance (1.2)
`
`The guidance addresses the information to be submitted in registration applications for new
`molecular entities and associated drug products. This guidance does not currently seek to cover
`the information to be submitted for abbreviated or abridged applications, variations, or clinical
`trial applications.
`
`Specific details of the sampling and testing for particular dosage forms in their proposed
`container closures are not covered in this guidance.
`
`Further guidance on new dosage forms and on biotechnological/biological products can be found
`in ICH guidances Q1C Stability Testing for New Dosage Forms and Q5C Quality of
`Biotechnological Products: Stability Testing of Biotechnological/Biological Products,
`respectively.
`
`C.
`
`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 retest 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 guidance is based on an analysis of the effects of
`climatic conditions in the three regions of the EU, 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 guidance addresses climatic zones I and II. The
`principle has been established that stability information generated in any one of the three regions
`of the EU, Japan, and the United States would be mutually acceptable to the other two regions,
`provided the information is consistent with this guidance and the labeling is in accord with
`national/regional requirements.
`
`FDA's guidance documents, including this guidance, do not establish legally enforceable
`responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
`be viewed only as recommendations, unless specific regulatory or statutory requirements are
`cited. The use of the word should in Agency guidances means that something is suggested or
`recommended, but not required.
`
`II.
`
`GUIDANCE (2)
`
`A.
`
`1.
`
`Drug Substance (2.1)
`
`General (2.1.1)
`
`Information on the stability of the drug substance is an integral part of the systematic approach to
`stability evaluation.
`
`2
`
`

`

`Contains Nonbinding Recommendations
`
`2.
`
`Stress Testing (2.1.2)
`
`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. The testing
`should include the effect of temperatures (in 10°C increments (e.g., 50°C, 60°C) above that for
`accelerated testing), humidity (e.g., 75 percent relative humidity 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 Photostability Testing of
`New Drug Substances and Products.
`
`Examining degradation products under stress conditions is useful in establishing degradation
`pathways and developing and validating suitable analytical procedures. However, such
`examination may not be necessary 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.
`
`3.
`
`Selection of Batches (2.1.3)
`
`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 production batches 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.
`
`4.
`
`Container Closure System (2.1.4)
`
`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.
`
`5.
`
`Specification (2.1.5)
`
`Specification, which is a list of tests, references to analytical procedures, and proposed
`acceptance criteria, is addressed in ICH Q6A Specifications: Test Procedures and Acceptance
`Criteria for New Drug Substances and New Drug Products: Chemical Substances and Q6B
`
`3
`
`

`

`Contains Nonbinding Recommendations
`
`Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New
`Drug Products: Biotechnological/Biological Products. In addition, specification for degradation
`products in a drug substance is discussed in ICH Q3A Impurities in New Drug Substances.
`
`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 should depend on the results from validation
`studies.
`
`6.
`
`Testing Frequency (2.1.6)
`
`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 retest 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
`retest 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 the 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 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.
`
`7.
`
`Storage Conditions (2.1.7)
`
`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 retest 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 should apply if the drug substance
`
`4
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`

`Contains Nonbinding Recommendations
`
`is not specifically covered by a subsequent section. Alternative storage conditions can be used if
`justified.
`
`a.
`
`General case (2.1.7.1)
`
`Study
`
`Storage condition
`
`Minimum time period covered
`by data at submission
`12 months
`
`Long-term*
`
`25°C ± 2°C/60% RH ± 5% RH
`or
`30°C ± 2°C/65% RH ± 5% RH
`30°C ± 2°C/65% RH ± 5% RH 6 months
`Intermediate**
`40°C ± 2°C/75% RH ± 5% RH 6 months
`Accelerated
`* It is up to the applicant to decide whether long-term stability sturdies are performed at
`25°C ± 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.
`
`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.
`
`b.
`
`Drug substances intended for storage in a refrigerator (2.1.7.2)
`
`Study
`
`Long-term
`Accelerated
`
`Storage condition
`
`Minimum time period covered
`by data at submission
`12 months
`5°C ± 3°C
`25°C ± 2°C/60% RH ± 5% RH 6 months
`
`Data from refrigerated storage should be assessed according to the evaluation section of this
`guidance, except where explicitly noted below.
`
`If significant change occurs between 3 and 6 months’ testing at the accelerated storage condition,
`the proposed retest 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
`
`5
`
`

`

`Contains Nonbinding Recommendations
`
`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.
`
`c.
`
`Drug substances intended for storage in a freezer (2.1.7.3)
`
`Study
`
`Storage condition
`
`Long-term
`
`-20°C ± 5°C
`
`Minimum time period covered
`by data at submission
`12 months
`
`For drug substances intended for storage in a freezer, the retest 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).
`
`d.
`
`Drug substances intended for storage below -20°C (2.1.7.4)
`
`Drug substances intended for storage below -20°C should be treated on a case-by-case basis.
`
`8.
`
`Stability Commitment (2.1.8)
`
`When available long-term stability data on primary batches do not cover the proposed retest
`period granted at the time of approval, a commitment should be made to continue the stability
`studies postapproval to firmly establish the retest period.
`
`Where the submission includes long-term stability data on three production batches covering the
`proposed retest period, a postapproval 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
`batches, a commitment should be made to continue these studies through the
`proposed retest 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 retest period and to place additional production batches, to a
`total of at least three, on long-term stability studies through the proposed retest
`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 retest period.
`
`6
`
`

`

`Contains Nonbinding Recommendations
`
`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.
`
`9.
`
`Evaluation (2.1.9)
`
`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 retest 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 retest period.
`
`The data may show so little degradation and so little variability that it is apparent from looking at
`the data that the requested retest 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 percent, 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 retest period should be
`based on the minimum time a batch can be expected to remain within acceptance criteria.
`
`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 retest period can be undertaken at approval time if justified. This
`justification should be based, for example, 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, and/or existence of supporting stability data. 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.
`
`7
`
`

`

`Contains Nonbinding Recommendations
`
`10.
`
`Statements/Labeling (2.1.10)
`
`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 retest period should be derived from the stability information, and a retest date should be
`displayed on the container label if appropriate.
`
`B.
`
`1.
`
`Drug Product (2.2)
`
`General (2.2.1)
`
`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, results from stability studies on the drug
`substance, and 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.
`
`Photostability Testing (2.2.2)
`
`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.
`
`3.
`
` Selection of Batches (2.2.3)
`
`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.
`
`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.
`
`4.
`
`Container Closure System (2.2.4)
`
`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
`
`8
`
`

`

`Contains Nonbinding Recommendations
`
`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.
`
`5.
`
`Specification (2.2.5)
`
`Specification, which is a list of tests, references 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 ICH Q3B Impurities in New Drug Products.
`
`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.
`
`6.
`
`Testing Frequency (2.2.6)
`
`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.
`
`9
`
`

`

`Contains Nonbinding Recommendations
`
`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.
`
`7.
`
`Storage Conditions (2.2.7)
`
`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 should apply if the drug product is
`not specifically covered by a subsequent section. Alternative storage conditions can be used if
`justified.
`
`10
`
`

`

`Contains Nonbinding Recommendations
`
`a.
`
`General case (2.2.7.1)
`
`Study
`
`Storage condition
`
`Minimum time period covered
`by data at submission
`12 months
`
`Long-term*
`
`25°C ± 2°C/60% RH ± 5% RH
`or
`30°C ± 2°C/65% RH ± 5% RH
` 6 months
`30°C ± 2°C/65% RH ± 5% RH
`Intermediate**
` 6 months
`40°C ± 2°C/75% RH ± 5% RH
`Accelerated
`* It is up to the applicant to decide whether long-term stability sturdies are performed at
`25°C ± 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.
`
`If long-term studies are condcuted 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
`