The European Agency for the Evaluation of Medicinal Products
`Human Medicines Evaluation Unit
`
`CPMP/ICH/3 80/95
`
`ICH Topic Q 1 A
`Stability Testing Guidelines: Stability Testing of New Drug
`Substances and Products
`
`Step 5
`
`NOTE FOR GUIDANCE ON STABILITY TESTING: STABILITY
`TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS
`(CPMP/ICH/380/95)
`
`[This guideline replaces relevant section of previous guideline]
`
`J
`
`APPROVAL BY CPMP
`
`December 1993
`
`STUDIES CAN BE SUBMITTED ACCORDING TO THIS GUIDELINE
`
`January 1994
`
`DATE FOR COMING INTO OPERATION
`(DOSSIERS SUBMITTED AFTER)
`
`1 January 1998
`
`ICH- Technical Coordination- R. Bass
`7 Westferry Circus, Canary \Nharf, London E14 4HB, UK
`Tel: (+44-171)4188411 Fax: (+44-171)4188551
`E_Mail: mail@emea.eudra.org http://www.eudra.org/emea.html
`
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`STABILITY TESTING OF NEW DRUG SUBSTANCES
`AND PRODUCTS
`
`ICH Harmonised Tripartite Guideline
`[EMEA Status as ofDecember 1993]
`
`Preamble
`The following guideline sets out the stability testing requirement for a Registration
`Application within the three areas of the EC, Japan and the USA. It does not seek necessarily
`to cover the testing that may be required for registration in or export to other areas of the
`world.
`
`The guideline seeks to exemplify the core stability data package required for new drug
`It is not always necessary to follow this when there are
`substances and products.
`scientifically justifiable reasons for using alternative approaches.
`
`The guideline provides a general indication on the requirements for stability testing, but leaves
`sufficient flexibility to encompass the variety of different practical situations required for
`specific scientific situations and characteristics of the materials being evaluated.
`
`The principle that information on stability generated in any one ofthe three areas of the EC,
`Japan and the USA would be mutually acceptable in both of the other two areas has been
`established, provided it meets the appropriate requirements of this guideline and the labelling
`is in accord with nationaVregional requirements.
`
`Details ofthe specific requirements for sampling, test requirements for particular dosage
`forms/packaging etc., are not covered in this guideline.
`
`Objective
`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 enables recommended storage conditions, re-test
`periods and shelf lives to be established.
`
`Scope
`The guideline primarily addresses the information required in Registration Applications for
`new molecular entities and associated drug products.
`
`This guideline does not currently seek to cover the information required for abbreviated or
`abridged applications, variations, clinical trial applications, etc.
`
`The choice oftest conditions defined in this guideline is based on an analysis of the effects of
`climatic conditions in the three areas of the EC, Japan and the USA. The mean kinetic
`temperature in any region of the world can be derived from climatic data (Grimm, W. Drugs
`Made in Germany, 28, 196-202, 1985 and 29, 39-47, 1986).
`
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`DRUG SUBSTANCE
`
`General
`Information on the stability of the drug substance is an integral part of the systematic
`approach to stability evaluation.
`
`Stress Testing
`Stress testing helps to determine the intrinsic stability of the molecule by establishing
`degradation pathways in order to identifY the likely degradation products and to validate the
`stability indicating power of the analytical procedures used.
`
`Formal Studies
`Primary stability studies are intended to show that the drug substance will remain within
`specification during the re-test period if stored under recommended storage conditions.
`
`Selection of Batches
`Stability information from accelerated and long term testing is to be provided on at least three
`batches. The long term testing should cover a minimum of 12 months duration on at least
`three batches at the time of submission.
`
`The batches manufactured to a minimum of pilot plant scale should be by the same synthetic
`route and use a method of manufacture and procedure that simulates the final process to be
`used on a manufacturing scale.
`
`The overall quality of the batches of drug substance placed on stability should be
`representative of both the quality of the material used in pre-clinical and clinical studies and
`the quality of material to be made on a manufacturing scale.
`
`Supporting information may be provided using stability data on batches of drug substance
`made on a laboratory scale.
`
`The first three production batches of drug substance manufactured post approval, if not
`submitted in the original Registration Application, should be placed on long term stability
`studies using the same stability protocol as in the approved drug application.
`
`Test Procedures and Test Criteria
`The testing should cover those features susceptible to change during storage and likely to
`influence quality, safety and/or efficacy. Stability information should cover as necessary the
`physical, chemical and microbiological test characteristics. Validated stability-indicating
`testing methods must be applied. The need for the extent of replication will depend on the
`results of validation studies.
`
`Specification
`Limits of acceptability should be derived from the profile of the material as used in the pre(cid:173)
`clinical and clinical batches. It will need to include individual and total upper limits for
`impurities and degradation products, the justification for which should be influenced by the
`levels observed in material used in pre-clinical studies and clinical trials.
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`Storage Conditions
`The length of the studies and. the storage conditions should be sufficient to cover storage,
`shipment and subsequent use. Application of the same storage conditions as applied to the
`drug product will facilitate comparative review and assessment. Other storage conditions are
`allowable if justified. In particular, temperature sensitive drug substances should be stored
`under an alternative, lower temperature condition which will then become the designated long
`term testing storage temperature. The six months accelerated testing should then be carried
`out at a temperature at least 15°C above this designated long term storage temperature
`(together with the appropriate relative humidity conditions for that temperature). The
`designated long term testing conditions will be reflected in the labelling and re-test date.
`
`Conditions
`
`Long term testing
`
`Minimum Time
`Period at Submission
`
`12 Months
`
`Accelerated Testing
`
`6 Months
`
`Where 'significant change' occurs during six months storage under conditions of accelerated
`testing at 40°C ± 2°C/75 percent RH ± 5 percent, additional testing at an intermediate
`condition (such as 30°C ± 2°C/60 percent RH ± 5 percent) should be conducted for drug
`substances to be used in the manufacture of dosage forms tested long term at 25°C/60 percent
`RH and this information included in the Registration Application. The initial Registration
`Application should include a minimum of 6 months data from a 12 months study.
`
`'Significant change' at 40°C/75 percent RH or 30°C/60 percent RH is defined as failure to meet
`the specification.
`
`The long term testing will be continued for a sufficient period of time beyond 12 months to
`cover all appropriate re-test periods, and the further accumulated data can be submitted to the
`Authorities during the assessment period of the Registration Application.
`
`The data (from accelerated testing or from testing at an intermediate condition) may be used to
`evaluate the impact of short term excursions outside the label storage conditions such as might
`occur during shipping.
`
`Testing Frequency
`Frequency of testing should be sufficient to establish the stability characteristics of the drug
`substance. Testing under the defined long term conditions will normally be every three
`months, over the first year, every six months over the second year and then annually.
`
`Packaging/Containers
`The containers to be used in the long term, real time stability evaluation should be the same as
`or simulate the actual packaging used for storage and distribution.
`
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`Evaluation
`The design of the stability study is to establish, based on testing a minimum of three batches
`of the drug substance and evaluating the stability information (covering as necessary the
`physical, chemical and microbiological test characteristics), a retest period applicable to all
`future batches of the bulk drug substance manufactured under similar circumstances. The
`degree ofvariability of individual batches affects the confidence that a future production batch
`will remain within specification until the retest date.
`
`An acceptable approach for quantitative characteristics that are expected to decrease with time
`is to determine the time at which the 95% one-sided confidence limit for the mean degradation
`curve intersects the acceptable lower specification limit. If analysis shows that the batch to
`batch variability is small, it is advantageous to combine the data into one overall estimate and
`this can be done by first applying appropriate statistical tests (for example, p values for level
`of significance of rejection ofmore than 0.25) to the slopes ofthe regression lines and zero
`time intercepts for the individual batches. If it is inappropriate to combine data from several
`batches, the overall retest period may depend on the minimum time a batch may be expected
`to remain within acceptable and justified limits.
`
`The nature of any degradation relationship will determine the need for transformation of the
`data 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.
`
`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 the circumstances,
`it is normally unnecessary to go through the formal statistical analysis but merely to provide a
`full justification for the omission.
`
`Limited extrapolation of the real time data beyond the observed range to extend expiration
`dating at approval time, particularly where the accelerated data supports this, may be
`undertaken. However, this assumes that the same degradation relationship will continue to
`apply beyond the observed data and hence the use of extrapolation must be justified in each
`application in terms of what is known about the mechanism of degradation, the goodness of fit
`of any mathematical model, batch size, existence of supportive data etc.
`
`Any evaluation should cover not only the assay, but the levels of degradation products and
`other appropriate attributes.
`
`Statements/ Labelling
`A storage temperature range may be used in accordance with relevant national/regional
`requirements. The range should be based on the stability evaluation of the drug substance.
`Where applicable, specific requirements should be stated, particularly for drug substances that
`cannot tolerate freezing. The use of terms such as 'ambient conditions' or 'room temperature'
`is unacceptable.
`
`A re-test period should be derived from.the stability information.
`
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`DRUG PRODUCT
`
`General
`The design of the stability programme for the finished product should be based on the
`knowledge of the behavior and properties of the drug substance and the experience gained
`from clinical formulation studies and from the stability studies on the drug substance. The
`likely changes on storage and the rationale for the selection of product variables to include in
`the testing programme should be stated.
`
`Selection of Batches
`Stability information from accelerated and long term testing is to be provided on three batches
`of the same formulation and dosage form in the containers and closure proposed for marketing.
`Two of the three batches should be at least pilot scale. The third batch may be smaller (e.g.,
`25,000 to 50,000 tablets or capsules for solid oral dosage forms). The long term testing should
`cover at least 12 months duration at the time of submission. The manufacturing process to be
`used should meaningfully simulate that which would be applied to large scale batches for
`marketing. The process should provide product of the same quality intended for marketing,
`and meeting the same quality specification as to be applied for release of material. Where
`possible, batches of the finished product should be manufactured using identifiably different
`batches of drug substance.
`
`Data on laboratory scale batches is not acceptable as primary stability information. Data on
`associated formulations or packaging may be submitted as supportive information. The first
`three production batches manufactured post approval, if not submitted in the original
`Registration Application, should be placed on accelerated and long term stability studies using
`the same stability protocols as in the approved drug application.
`
`Test Procedures and Test Criteria
`The testing should cover those features susceptible to change during storage and likely to
`influence quality, safety and/or efficacy. Analytical test procedures should be fully validated
`and the assays should be stability-indicating. The need for the extent of replication will
`depend on the results of validation studies.
`
`The range of testing should cover not only chemical and biological stability but also loss of
`preservative, physical properties and characteristics, organoleptic properties and where
`required, microbiological attributes. Preservative efficacy testing and assays on stored
`samples should be carried out to determine the content and efficacy of antimicrobial
`preservatives.
`
`Specifications
`Limits of acceptance should relate to the release limits (where applicable), to be derived from
`consideration of all the available stability information. The shelf life specification could allow
`acceptable and justifiable derivations from the release specification based on the stability
`evaluation and the changes observed on storage. It will need to include specific upper limits
`for degradation products, the justification for which should be influenced by the levels
`observed in material used in pre-clinical studies and clinical trials. The justification for the
`limits proposed for certain other tests such as particle size and/or dissolution rate will require
`reference to the results observed for batch(es) used in bioavailability and/or clinical studies.
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`Any differences between the release and shelf life specifications for antimicrobial
`preservatives should be supported by preservative efficacy testing.
`
`Storage Test Conditions
`The length of the studies and the storage conditions should be sufficient to cover storage,
`shipment and subsequent use (e.g., reconstitution or dilution as recommended in the labelling).
`
`See Table below for accelerated and long term storage conditions and minimum times. An
`assurance that long term testing will continue to cover the expected shelf life should be
`provided.
`.
`
`Other storage conditions are allowable if justified. Heat sensitive drug products should be
`stored under an alternative lower temperature condition which will eventually become the
`designated long term storage temperature. Special consideration may need to be given to
`products which change physically or even chemically at lower storage conditions e.g.,
`suspensions or emulsions which may sediment or cream, oils and semi-solid preparations
`which may show an increased viscosity. Where a lower temperature condition is used, the six
`months accelerated testing should be carried out at a temperature at least l5°C above its
`designated long term storage temperature (together with appropriate relative humidity
`conditions for that temperature). For example, for a product to be stored long term under
`refrigerated conditions, accelerated testing should be conducted at 25°C ± 2°C/60 percent RH
`± 5 percent RH. The designated long term testing conditions will be reflected in the labelling
`and expiration date.
`
`Storage under conditions of high relative humidities applies particularly to solid dosage forms.
`For products such as solutions, suspensions etc., contained in packs designed to provide a
`permanent barrier to water loss, specific storage under conditions of high relative humidity is
`not necessary but the same range of temperatures should be applied. Low relative humidity
`(e.g., I 0 - 20 percent RH) can adversely affect products packed in semi-permeable containers
`(e.g. solutions in plastic bags, nose drops in small plastic containers etc.) and consideration
`should be given to appropriate testing under such conditions.
`
`Conditions
`
`Minimum Time
`Period at Submission
`
`Long term testing
`
`25°C ± 2°C/60% RH ± 5%
`
`Accelerated Testing
`
`40°C ± 2°C/75% RH ± 5%
`
`12 Months
`
`6 Months
`
`Where 'significant change' occurs due to accelerated testing, additional testing at an
`intermediate condition e.g., 30°C ± 2°C/60 percent± 5 percent RH should be conducted.
`'Significant change' at the accelerated condition is defined as:
`
`1. A 5 percent potency loss from the initial assay value of a batch;
`
`2. Any specified degradant exceeding its specification limit;
`
`3.
`
`The product exceeding its pH limits;
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`4. Dissolution exceeding the specification limits for 12 capsules or tablets.
`
`5.
`
`Failure to meet specifications for appearance and physical properties e.g., color, phase
`separation, resuspendibility, delivery per actuation, caking, hardness, etc.
`
`initial Registration
`Should significant change occur at 40°C/75 percent RH then the
`Application should include a minimum of 6 months data from an ongoing one year study at
`30°C/60 percent RH; the same significant change criteria shall then apply.
`
`The long term testing will be continued for a sufficient time beyond 12 months to cover shelf
`life at appropriate test periods. The further accumulated data should be submitted to the
`authorities during the assessment period of the Registration Application.
`
`The first three production batches manufactured post approval, if not submitted in the
`original Registration Application, should be placed on accelerated and long term stability
`studies using the same stability protocol as in the approved drug application.
`
`Testing Frequency
`Frequency of testing should be sufficient to establish the stability characteristics ofthe drug
`product. Testing will normally be every three months over the first year, every six months
`over the second year and then annually.
`
`The use ofmatrixing or bracketing can be applied, if justified. (See Glossary).
`
`Packaging Materials
`The testing should be carried out in the final packaging proposed for marketing. Additional
`testing of unprotected drug product can form a useful part of the stress testing and pack
`evaluation, as can studies carried out in other related packaging materials in supporting the
`definitive pack(s).
`
`Evaluation
`A systematic approach should be adopted in the presentation and evaluation of the stability
`information which should cover as necessary physical, chemical, biological, microbiological
`quality characteristics, including particular properties of the dosage form (for example
`dissolution rate for oral solid dose forms).
`
`The design of the stability study is to establish, based on testing a minimum of three batches
`of the drug product, a shelf-life and label storage instructions applicable to all future batches
`of the dosage form manufactured and packed under similar circumstances. The degree of
`variability of individual batches affects the confidence that a future production batch will
`remain within specification until the expiration date.
`
`An acceptable approach for quantitative characteristics that are expected to decrease with time
`is to determine the time at which the 95% one-sided confidence limit for the mean degradation
`curve intersects the acceptable lower specification limit. If analysis shows that the batch to
`batch variability is small, it is advantageous to combine the data into one overall estimate and
`this can be done by first applying appropriate statistical tests (for example, p values for level
`of significance ofrejection ofmore than 0.25) to the slopes ofthe regression lines and zero
`time intercepts for the individual batches. If it is inappropriate to combine data from several
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`batches, the overall shelf-life may depend on the minimum time a batch may be expected to
`remain within acceptable and justified limits.
`
`The nature of the degradation relationship will determine the need for transformation of the
`data 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 on all batches and combined batches (where appropriate)
`to the assumed degradation line or curve.
`
`Where the data shows so little degradation and so little variability that it is apparent from
`looking at the data that the requested shelf-life will be granted, it is normally unnecessary to
`go through the formal statistical analysis but only to provide a justification for the omission.
`
`Limited extrapolation of the real time data beyond the observed range to extend expiration
`dating at approval time, particularly where the accelerated data supports this, may be
`undertaken. However, this assumes that the same degradation relationship will continue to
`apply beyond the observed data and hence the use of extrapolation must be justified in each
`application in terms of what is known about the mechanisms of degradation, the goodness of
`fit of any mathematical model, batch size, existence of supportive data, etc.
`
`Any evaluation should consider not only the assay, but the levels of degradation products and
`appropriate attributes. Where appropriate, attention should be paid to reviewing the adequacy
`of the mass balance, different stability and degradation performance.
`
`The stability of the drug products after reconstituting or diluting according to labelling, should
`be addressed to provide appropriate and supportive information.
`
`Statements/Labelling
`A storage temperature range may be used in accordance with relevant national/regional
`requirements .. The range should be based on the stability evaluation of the drug product.
`Where applicable, specific requirements should be stated particularly for drug products that
`cannot tolerate freezing.
`
`The use of terms such as 'ambient conditions' or 'room temperature' is unacceptable.
`
`There should be a direct linkage between the label statement and the demonstrated stability
`characteristics of the drug product.
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`ANNEX1
`
`GLOSSARY AND INFORMATION
`The following terms have been in general use and the following definitions are provided to
`facilitate interpretation of the guideline.
`
`Accelerated Testing
`Studies designed to increase the rate of chemical degradation or physical change of an active
`drug substance or drug product by using exaggerated storage conditions as part of the formal,
`defmitive, storage programme.
`
`These data, in addition to long term stability studies, may also be used to assess longer term
`chemical effects at non-accelerated conditions and to evaluate the impact of short term
`excursions outside the label storage conditions such as might occur during shipping. Results
`from accelerated testing studies are not always predictive of physical changes.
`
`Active Substance; Active Ingredient; Drug Substance; Medicinal Substance
`The unformulated drug substance which may be subsequently formulated with excipients to
`produce the drug product.
`
`Bracketing
`The design of a stability schedule so that at any time point only the samples on the extremes,
`for example of container size and/or dosage strengths, are tested. The design assumes that the
`stability of the intermediate condition samples are represented by those at the extremes.
`
`Where a range of dosage strengths is to be tested, bracketing designs may be particularly
`applicable if the strengths are very closely related in composition (e.g., for a tablet range made
`with different compression weights of a similar basic granulation, or a capsule range made by
`filling different plug fill weights of the same basic composition into different size capsule
`shells). Where a range of sizes of immediate containers are to be evaluated, bracketing designs
`may be applicable if the material of composition of the container and the type of closure are
`the same throughout the range.
`
`Climatic Zones
`The concept of dividing the world into four zones based on defining the prevalent annual
`climatic conditions.
`
`Dosage Form; Preparation
`A pharmaceutical product type, for example tablet, capsule, solution, cream etc. that contains
`a drug ingredient generally, but not necessarily, in association with excipients.
`
`Drug Product; Finished Product
`The dosage form in the fmal immediate packaging intended for marketing.
`
`Excipient
`Anything other than the drug substance in the dosage form.
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`Expiry/Expiration Date
`The date placed on the container/labels of a drug product designating the time during which a
`batch of the product is expected to remain within the approved shelf-life specification if
`stored under defmed conditions, and after which it must not be used.
`
`Formal (Systematic) Studies
`Formal studies are those undertaken to a pre-approval stability protocol which embraces the
`principles of these guidelines.
`
`Long Term (Real Time) Testing
`Stability evaluation of the physical, chemical, biological and microbiological characteristics of a
`drug product and a drug substance, covering the expected duration of the shelf life and re-test
`period, which are claimed in the submission and will appear on the labelling.
`
`M~ss Balance; Material Balance
`The process of adding together the assay value and levels of degradation products to see how
`closely these add up to 100 per cent ofthe initial value, with due consideration ofthe margin
`of analytical precision.
`
`This concept is a useful scientific guide for evaluating data but it is not achievable in all
`circumstances. The focus may instead be on assuring the specificity of the assay, the
`completeness ofthe investigation of routes of degradation, and the use, if necessary, of
`identified degradants as indicators of the extent of degradation via particular mechanisms.
`
`Matrixing
`The statistical design of a stability schedule so that only a fraction of the total number of
`samples are tested at any specified sampling point. At a subsequent sampling point, different
`sets of samples of the total number would be tested. The design assumes that the stability of
`the samples tested represents the stability of all samples. The differences in the samples for
`the same drug product should be identified as, for example, covering different batches,
`different strengths, different sizes of the same container and closure and possibly in some
`cases different container/closure systems.
`
`Matrixing can cover reduced testing when more than one variable is being evaluated. Thus the
`design of the matrix will be dictated by the factors needing to be covered and evaluated. This
`potential complexity precludes inclusion of specific details and examples, and it may be
`desirable to discuss design in advance with the Regulatory Authority, where this is possible.
`In every case it is essential that all batches are tested initially and at the end of the long term
`testing.
`
`Mean Kinetic Temperature
`When establishing the mean value of the temperature, the formula of J.D. Haynes (J. Pharm.
`Sci. 60, 927-929, 1971) can be used to calculate the mean kinetic temperature. It is higher than
`the arithmetic mean temperature and takes into account the Arrhenius equation from which
`Haynes derived his formula.
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`New Molecular Entity; New Active Substance
`A substance which has not previously been registered as a new drug substance with the
`national or regional authority concerned.
`
`Pilot Plant Scale
`The manufacture of either drug substance or drug product by a procedure fully representative
`of and simulating that to be applied on a full manufacturing scale.
`
`For oral solid dosage forms this is generally taken to be at a minimum scale of one tenth that
`of full production or 100,000 tablets or capsules, whichever is the larger.
`
`Primary Stability Data
`Data on the drug substance stored in the proposed packaging under storage conditions that
`support the proposed re-test date.
`
`Data on the drug product stored in the proposed container-closure for marketing under storage
`conditions that support the proposed shelf life.
`
`Re-Test Date
`The date when samples of the drug substance should be re-examined to ensure that material is
`still suitable for use.
`
`Re-Test Period
`The period of time during which the drug substance can be considered to remain within the
`specification and therefore acceptable for use in the manufacture of a given drug product,
`provided that it has been stored under the defined conditions; after this period, the batch
`should be retested for compliance with specification and then used immediately.
`
`Shelf-life; Expiration Dating Period
`The time interval that a drug product is expected to remain within the approved shelf-life
`specification provided that it is stored under the conditions defined on the label in the
`proposed containers and closure.
`
`Specification - Release
`The combination of physical, chemical, biological and microbiological test requirements that
`determine a drug product is suitable for release at the time of its manufacture.
`
`Specification - Check/Shelf-life
`The combination of physical, chemical, biological and microbiological test requirements that a
`drug substance must meet up to its re-test date or a drug product must meet throughout its
`shelf life.
`
`Storage Conditions Tolerances
`The acceptable variation in temperature and relative humidity of storage facilities.
`
`The equipment must be capable of controlling temperature to a range of ±2° C and Relative
`Humidity to ±5% RH. The actual temperatures and humidities should be monitored during
`stability storage. Short term spikes due to opening of doors of the storage facility are
`
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`accepted as unavoidable. The effect of excursions due to equipment failure should be
`addressed by the applicant and reported if judged to impact stability results. Excursions that
`exceed these ranges (i.e., ±2°C and/or ±5 percent RH) for more than 24 hours should be
`described in the study report and their impact assessed.
`
`Stress Testing (Drug Substance)
`These studies are undertaken to elucidate intrinsic stability characteristics. Such testing is
`part of the development strategy and is normally carried out under more severe conditions
`than those used for accelerated tests.
`
`Stress testing is conducted to provide data on forced decomposition products and
`decomposition mechanisms for the drug substance. The severe conditions that may be
`encountered during distribution can be covered by stress testing of definitive batches of drug
`substance.
`
`These studies should establish the inherent stability characteristics of the molecule, such as
`the degradation pathways, and lead to identification of degradation products and hence
`support the suitability of the proposed analytical procedures. The detailed nature of the
`studies will depend on the individual drug substance and type of drug product.
`
`This testing is likely to be carried out on a single batch of materi