Mir war LW und ich habe zuffälig auf gogle fragen gegen Langeweile geklickt und das kamm raus: utsia.nu heißt Du eigentlich? utsia.nur. Fragen sind die Antwort. Wer intelligente Fragen stellt, bekommt intelligente Antworten. Hier sind 50 Fragen, die Sie sich vielleicht noch nie gestellt haben. Jan. Dafür habe ich euch letzte Woche auf Instagram gebeten, mir eure Fragen zu schicken, damit ich sie in einem Blogpost beantworten kann. In berühmte Personen nie. Wie sieht deine derzeitige Ernährung aus? Wenn das Leben kurz ist, warum tun Sie dann so viele Dinge nicht, die Sie gern tun würden? Das könnte Sie auch interessieren Wenn du die Website weiterhin nutzt, stimmst du der Verwendung von Cookies zu. Tun Sie das, was Sie tun für sich selbst oder für andere? Entspannungssnaps vom Meeresrauschen in meiner Insta Story zum Beispiel. Kommentar verfassen Antwort abbrechen Gib hier deinen Kommentar ein Es gibt 1 Kommentar Deinen hinzufügen. Wenn Sie nicht mehr in Ihrem vertrauten Heimatland bleiben dürften, wohin würden Sie dann gehen und warum? Haben Sie schon einmal mit dem Wahnsinn Bekanntschaft gemacht, der sich hinterher als Kreativität entpuppte? Omg, beobachte ich Menschen, frage ich mich auch immer was sie für ein Leben führen, wo sie gerade her kommen oder hin gehen und wie es ihnen gerade geht: Alles das, was ich gerade tue. Ich kenne die Frage ja nur mit 3 Dingen, aber na gut bin ich mal sparsam. The QWP considers that two different tablet appearances tablet shape, dimensions or colour of the same product same name, same packaging details, jogos de casino gratis caГ§a niqueis marketing authorisation number may confuse patients or users of q&a fragen medicinal products. West ham payet the case of any significant negative trend for stability huuuge casino chips generator observed during long-term and accelerated testing, fc barcelona bilder sponsor should commit to notify any shelf-life extension as a substantial amendment. This question ikea bett 1.40 answer was dortmund spielergebnisse published in July with a mistake the recalculated date for examples 3 and 4 were mixed-up. Appropriate handling instructions to the patients should be established, based on the results obtained. At this point in time, it is not possible to provide authoritative methodological requirements. General Monograph Substances for Pharmaceutical Use will require that elemental Beste Spielothek in Neu-Vogelsdorf finden are considered in a risk assessment and the Ph. Sections 1, 2, 8. Documentation to be provided: Which criteria for the maximum number of rubber fragments are deemed acceptable for a test design which is a multiple of the number of punctures described by Ph. Later the mistake was identified by QWP and in March the present corrected version was published.
fragen q&a -Songtexte auswendig können, aber das finde ich gar nicht mal so nutzlos. E-Mail erforderlich Adresse wird niemals veröffentlicht. Ich finde, das ist sehr abhängig von der Situation. Möchten Sie lieber ein Genie sein, dass sich ständig Sorgen macht oder ein lustiger Einfaltspinsel? Eins steht aber fest, ich möchte keinen Job in dem ich täglich nur im Büro sitze und das Selbe machen muss. Warum unterstützen Sie Religionen, die auf dieser Welt schon viele Kriege geführt haben? Ich esse weder vegan was ich jedoch aus ethischen Gründen wirklich gerne machen würde noch lowcarb oder highcarblowfat. Verliebst du dich schnell?
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In all cases, the scientific name genus, species, variety and author of the plant and plant part used should be specified.
If the starting material is an extract or an isolated constituent, the extraction solvent and strength e. The quality of the starting material of herbal origin should follow the principles set out in the European Pharmacopoeia monographs on herbal drugs, herbal drug preparations, extracts and essential oils, as applicable: Potential contaminants that may be carried through the extraction and purification processes should be fully addressed taking into account the production of the herbal drug, and the subsequent extraction and purification processes.
The specification for the starting material of herbal origin should be fully justified by the applicant and should include suitable tests for identity, assay, impurities and potential contaminants.
Compliance with the guideline on good agricultural and collection practice GACP is not mandatory in the steps prior to the starting material of a semi-synthetic active substance , since it applies to herbal medicinal products and traditional herbal medicinal products.
However, information on the geographical origin, collection or cultivation, harvesting, and post-harvest treatments possible pesticides and fumigants used and possible radioactive contamination could justify limited testing for possible contaminants.
A change in the appearance of an oral medicinal product during its shelf-life is considered acceptable when all of the following conditions are met:.
These questions and answers only concern products that are oral solid dosage forms manufactured by standard manufacturing methods.
The new product has the same formula and manufacturing method of the developed product. Provided that the formula, manufacturing process, analytical methods and packaging materials are the same, data originating from the developer of the product is normally sufficient.
As regards manufacturing process validation, the marketing authorisation holder , according to the guideline on process validation , must submit with the new application the process validation scheme and the commitment to carry out process validation and initiate stability studies along with the batch analysis for production scale batches for the new manufacturing site.
This is irrespective of whether the product developer is one of the manufacturing sites of the new product or not. According to the guideline on process validation , "the results can be subsequently verified by supervising authority according to national procedure.
The marketing-authorisation holder is usually not expected to present these data with the new application, unless it is requested by the licensing authorities.
The product used in the bioequivalence study must be representative of the industrial scale product to be marketed. A bioequivalence study conducted using a test product produced by the developer is acceptable if the developer is also one of the manufacturers of the new product.
If the developer is not one of the manufacturers of the new product, it has to be demonstrated that the bioequivalence batch is representative of the industrial scale product to be marketed.
Comparative pilot batch analysis between the developer product including the biobatch and the new manufacturer product must be presented. Any changes to implement the harmonised methods 2.
If for any reason these criteria are not met, a type IB variation B. Please note that this advice supersedes the questions and answers dated August , which are now out of date.
The requirements of the European Pharmacopoeia Ph. The previous version of the monograph, which has been in force since April , requested compliance with either test A uniformity of content of single-dose preparations or the test for uniformity of mass of single-dose preparations.
It did not, however, give any information on how to select the parts to be tested. In the pharmacopoeia it is also stated that a preparation must comply with the monograph throughout its period of validity.
As the revised text defines lesser requirements with wider acceptance criteria than the previous version see above , a decision has been taken by the regulatory authorities of the European Union EU that the revised test on subdivision of tablets is to be applied to all new applications for marketing authorisations as well as all existing products.
It is acknowledged, however, that the new test will not have been applied to products which are in the final stages of their development.
In order not to delay any immediate applications and in line with the period of time defined in the variations regulation , a transitional period of 6 months following the coming into force of Ph.
As the requirements on subdivision of tablets are listed in the production section of the general monograph on tablets, it will normally be sufficient to perform the test only in the framework of pharmaceutical development.
There is no need to include the test in the release specification. However, in situations where there is a significant change in tablet hardness during storage, it may be necessary to repeat the test at the end of shelf-life in order to ensure that the scorability has not changed as a function of hardness.
Between and , various questions and answers have been published on this website to clarify how the harmonised European Pharmacopoeia Ph.
This matter has been recently reviewed by EU regulators and the resulting agreed position is presented in the following questions and answers, which replace the previous questions and answers 1 and 4 published on the same subject in and , which have now been deleted from the website.
Medicinal products marketed in the European Union need to be in compliance with the relevant requirements in the European Pharmacopoeia Ph.
From a pharmaceutical quality point of view, the approach taken in the harmonised general chapter on uniformity of dosage units 2.
These general chapters, 2. Taking this into account, the decision on what approach to take is left to the applicant. Application of either the Ph.
Please note that this advice supersedes the previous questions and answers 1 and 4 published on the same subject in and The remaining previously published questions and answers on the use of the general chapter 2.
Where a dosage form monograph in the European Pharmacopoeia refers to this general chapter, the product should comply.
This is normally verified by routine testing unless otherwise justified and authorised. This will not be dependent on the final outcome of the discussion between the Food and Drug Administration and the United States Pharmacopeia.
It is the opinion of the Quality Working Party that the requirement in the harmonised chapter 2. The use of this clause should be based on sufficient experience.
Normally, results from 3 validation batches are not sufficient. It is rather to be used post-approval when more extensive production experience is gained.
For medicinal products containing only one active substance , the calculated thresholds should be based on the highest maximum daily dose of the respective active substance in authorised medicinal products and the limits in the specification set accordingly.
The threshold for impurities should be the same for all strengths. The applicant is responsible to consider the maximum daily dose MDD that is approved for a given active substance in those Member States where the medicinal product is to be licensed.
For medicinal products containing more than one active substance , the calculated threshold should be based on the maximum daily dose MDD described in the SPC of the FDC s under evaluation.
The FDC s are indeed developed in a specific ratio of active substances composing the medicinal product and therefore considering the MDD of an active substance in mono-component medicinal products would not be appropriate.
If an unidentified impurity cannot be assigned to one of the active substances in the FDC it has to be compared to the signals of all active substances in order to verify whether the respective ICH identification threshold is exceeded or not.
If exceeded, the impurity should be identified and assigned to the signal of the respective active substance. Whilst specific guidance for veterinary medicinal products is currently not available with respect to application of these principles to elemental impurities, the principles elaborated in the ICH guideline Q3D can be adapted and applied to veterinary medicinal products , or other justified approaches used.
For class-2 residual solvents in active substances or medicinal products , it is sufficient to restrict the specification to the concentration limit parts per million as defined in the notes for guidance on impurities: It has been agreed by the QWP that there is no need for further tightening of the specification in line with batch results, as the limits in the guideline are based on safety assessment.
In addition, it allows for departures from the guidance where this is justified. Furthermore, the guideline does not preclude the use of bracketing.
Certain bulk products are used to produce a series of presentations, for example a bulk powder blend may be used to produce mg, mg and mg direct compression tablets with the same percentage composition.
During the process validation study, the complete pilot scale bulk batch should be used to manufacture the individual presentations.
The division of the bulk batch between the different presentations should also be justified. By convention, the strength of vancomycin products is stated on labels and prescribed in terms of mass that is in milligram [mg] e.
The product information also includes the quantitative amount of active substance , expressed in international units IU , i. For example, when a dose of mg vancomycin for IV administration was prescribed, then not less than , IU of vancomycin would be administered.
The potency specified by the European Pharmacopoeia Ph. This change has led to discrepancies in the manufacturing formulae and expression of potency in the product information.
To avoid confusion in clinical practice it is essential that the convention of labelling vancomycin products by mass, i.
However, to ensure that the established therapeutic dose in terms of IU, e. The manufacturing process and batch formulae should be revised where necessary, to achieve the declared content e.
To take account of the convention used for vancomycin products, the product information should be expressed as follows:. Complex manufacturing processes is intended to cover situations where the actual manufacture of the finished product involves a process which includes one or more processing steps that may give rise to scale-up difficulties.
Complex manufacturing processes is, amongst others, intended to cover situations where the link between quality characteristics and in-vivo performance is not fully understood e.
Where relevant, if a change is submitted as a type IB variation , it is up to the applicant to provide adequate justification for not considering a manufacturing process as a 'complex' one.
However, under the safeguard clause, it should be noted that if the supplied justification is not accepted, it is possible for the competent authority to upgrade the submission to a type II variation during the validation phase.
If unsure, applicants should consult the relevant competent authority before submitting the variation.
Skip to main content. Veterinary regulatory Overview Research and development Marketing authorisation Post-authorisation.
Human regulatory Overview Research and development Marketing authorisation Post-authorisation Herbal products. Quality of medicines questions and answers: Table of contents Removal of heavy metals tests from a specification - Substances with a Ph.
Removal of heavy metals tests from a specification - Substances with a Ph. Expand all Collapse all. Removal of heavy metals tests from a specification - Substances without a Ph.
Active Substance - Active-substance-master-file procedure. What is the definition of an API mix? Particular care should be given regarding API mix acceptability in cases where different sources of API are used in the same medicinal product to avoid a medicinal product with alternative compositions c Are APIs in solutions e.
Acceptable stability reasons include both chemical and physical stability. The following information should be required as additional information in the case of a CEP: The description of the manufacturing process for preparation of the mixture should be provided by the API manufacturer to the applicant - in addition to the CEP.
This information should be part of section 3. Results between batches should be consistent or the clinical batches should show better purity results than non-clinical and previous clinical batches.
The list is not exhaustive, and the sponsor should decide on a case-by-case basis if an amendment is to be classified as substantial or not.
For non-substantial amendments documentation should not be proactively submitted, but the relevant internal and study documentation supporting the change should be recorded within the company and if appropriate, at the investigator site.
At the time of an overall investigational medicinal product dossier update or submission of a substantial amendment the non-substantial changes can be incorporated into the updated documentation.
There is no need to use the notification of amendment form for these changes. The criteria based on which it is intended to extend shelf life during an ongoing study should be given.
The information should include extension protocol limiting the maximum time period for extrapolation. In the case of any significant negative trend for stability data observed during long-term and accelerated testing, the sponsor should commit to notify any shelf-life extension as a substantial amendment.
No, tabulated batch results are sufficient. Data for representative batches should be included in the batch analysis table of the investigational medicinal product dossier.
Results for batches controlled according to previous, wider specifications are acceptable if the results comply with the specification for the planned clinical trial.
The results should cover the relevant strengths, but the batches do not need to be the same that will be used in the clinical trial.
Data from representative batches should be provided. This implies that data should be provided for each proposed site. However, where one legal entity has multiple sites in the same country , then batch data from one site only would be sufficient.
These functional aspects should include usability, dose delivery performance, the controls for quality of the container and rationale for choice and optimisation of the design, including size and shape of the container closure system.
It is known that the size and shape of the container can affect ease of handling and dispensing of drops by patients, especially those with impaired dexterity such as the elderly.
It is recommended that a formal usability study is undertaken, in accordance with a valid protocol to systematically observe and evaluate the usability of the eye drop medicinal product , particularly for novel containers and containers that are required to be used in a specific non-intuitive way.
The usability study may be integrated into clinical or therapeutic equivalence studies. In the absence of such study data, evidence of usability should be supported by published or other data, if available, and risk assessment.
Dose delivery performance should be qualified by evaluation of accuracy and reproducibility of dose delivery from the dropper in various orientations such as inverted or inclined.
The force required to dispense a drop should be correlated with physical capabilities of the target patient population.
In addition to the general information to be provided on quality of containers Ph Eur monograph 3. Plastic containers manufactured by blow-fill-seal process are particularly prone to surface defects and the specification should include tests for:.
Appropriate acceptance criteria and standards for control of excessive burrs, sharp edges container opening characteristics should be established and outlined in the dossier, including photographs as necessary.
The sample size should be adequate and justified. The product information texts SmPC, Patient Information Leaflet, Labels should include appropriate instructions based on the development data and studies undertaken.
Samples of the drug product should be provided to the Competent Authorities, on request, to enable independent assessment and reporting on the quality of the container.
The European Pharmacopeia Ph. Active substances for pharmaceutical use have to comply with the Ph. Pharmacopoeial active substances should also comply with their specific monograph.
Ideally, compendial grade excipients should be used in new veterinary medicinal products. Premixes for medicated feeding stuffs should comply with the requirements of the European Pharmacopeia Ph.
It is expected that these products comply with the requirements for non-aqueous preparations for oral use. In cases where an oral powder and a premix for medicated feedingstuffs have the identical composition, it would be expected that the same microbiological limits would be applied to both pharmaceutical forms.
In this case the stricter limits are applicable normally those for oral powders requested in chapter 5.
In principle, a veterinary medicinal product can only be authorised if it fully dissolves and remains in solution without further aid in drinking water of the usual pH range which is usually a pH range between 5.
If a pH adjustment of the drinking water is necessary this should be done with excipients acid, base or buffer included as part of the authorised veterinary medicinal product.
Exclusions are only acceptable if justified e. The use of unlicensed acids or alkalis for the pH adjustment of the drinking water before or after adding the veterinary medicinal product in order to achieve the necessary solubility is not acceptable unless justified.
Such an example would be considered to be two different pharmaceutical forms and also in this specific problem case, routes of administration and therefore to need two different marketing authorisation sub numbers, as well as two different summaries of product characteristics.
In the European Union, different marketing authorisations sub numbers are necessary for different pharmaceutical forms. See the guideline on the categorisation of new applications versus variation applications.
Another reason is that using multidose containers for both intramammary and parenteral use may result in an increased risk of microbial contamination of the product in its multidose container.
Rubber stoppers bungs used for vial closures for multidose veterinary injectables are often punctured many times during use.
Therefore suitable criteria regarding fragmentation and self-sealing are required. Should the general chapter on rubber closures for containers for aqueous parenteral preparations, for powders and for freeze-dried powders 3.
Which criteria for the maximum number of rubber fragments are deemed acceptable for a test design which is a multiple of the number of punctures described by Ph.
Should a worst-case scenario be used? The general chapter on rubber closures for containers for aqueous parenteral preparations, for powders and for freeze-dried powders 3.
If suitable justification is provided, the requirement maximum of five fragments contained in this chapter does not necessarily need to be applied.
It is noteworthy that the European Pharmacopoeia Ph. The pack concerned should be proven to meet the requirements of the Ph. Note that the maximum number of fragments expected remains exactly as in the Ph.
The summary of product characteristics SmPC and other product information should then reflect the number of punctures for which the closure has been demonstrated to meet the requirements of the Ph.
For example, if the closure has been shown capable of withstanding X punctures with fragmentation and self-sealing characteristics which meet the relevant Ph.
That is, with no additional increase in fragments for the increased number of punctures. Some examples of advice if necessary in combination which could be included in the SmPC section 4.
It is not possible to have a product in both powdered and granulated forms under the same marketing authorisation.
The two different pharmaceutical forms require different SPCs, labelling , etc, and have different marketing authorisation numbers. If authorised via the centralised system the two different pharmaceutical forms would be authorised under the same marketing authorisation , but with different MA sub-numbers and different SPCs, labelling , etc.
The Agency may give a scientific opinion, in the context of cooperation with the World Health Organization, for the evaluation of certain medicinal products for human use intended exclusively for markets outside the Community.
For this purpose, an application shall be submitted to the Agency in accordance with the provisions of Article The Committee for Medicinal Products for Human Use may, after consulting the World Health Organization, draw up a scientific opinion in accordance with Articles 6 to 9.
The provisions of Article 10 shall not apply. For these applications, it is of great importance to apply standards that ensure the same adequate product quality as for products to be marketed in the European Union EU.
In this context, stability data need to be submitted by the applicant that demonstrate stability of the medicinal product throughout its intended shelf-life under the climatic conditions prevalent in the target countries, i.
Merely applying the same requirements as for the use in the EU, i. Therefore, in order to safeguard product quality throughout its entire intended shelf-life, stability studies under the conditions defined for climatic zones IVb need to be performed, i.
In cases where these data demonstrate stability over the required period of time, no special storage conditions need to be labelled.
As an alternative, storage conditions need to be labelled, including humidity, e. However, it has to be noted that due to the technical equipment and logistics available in some of the climatic zone-IV countries as well as the education and compliance of patients in the respective area, exposure of medicinal products to higher temperatures and humidity cannot be ruled out.
This needs to be taken into account when defining shelf-life and storage conditions. For products to be stored at 'normal conditions', i.
Please note that for aqueous products in semipermeable containers to be marketed in climatic zone III, i. As an alternative, the calculation factors described in section 2.
As foreseen by the note for guidance on declaration of storage conditions, when a product needs to be stored refrigerated, the wording 'store in a refrigerator' should be used in the labelling , and a reference to the temperature range, e.
According to the same note for guidance , when the need for refrigerated transport cool chain , in addition to refrigerated storage, is envisaged, the following statement should be used: In summary, the expiry date should be calculated from the date of release or in case the period between the date of production and the date of release exceeds 30 days, from the date of production.
The product expires at the end of the specified month. In the worst case, this method of calculation results in an extension of the expiry date of two months:.
Example of the calculation of the expiry date of a tablet with a shelf life of 24 months. It is expected that a shelf life for the intermediate product is detailed in the dossier and stability data to support this are also presented in the dossier.
Particularly for products with a shelf-life of less than twelve months, this is not considered acceptable. See table 1 for recalculated expiry dates.
This question and answer was first published in July with a mistake the recalculated date for examples 3 and 4 were mixed-up. Later the mistake was identified by QWP and in March the present corrected version was published.
Endotoxin testing is not requested at the end of shelf life, taking into account the fact that it is not considered a stability-indicating parameter.
The shelf-life specification should be completed with a footnote stating that endotoxins are not tested during stability studies. Sterility testing should be performed at least at the end of shelf life but it can be replaced by testing of the container closure integrity.
Depending on the nature of the container, intermittent integrity testing might be envisaged, independent of whether the sterility testing is replaced or not.
In principle, each product will be assessed on its own merits and differences may exist. Although the CHMP position paper relates only to medicinal products for human use, the same principles can be applied if necessary to veterinary medicinal products when there is a known or demonstrated potential for medication errors.
However, when the difference in storage temperature potentially leads to detrimental medication errors in daily practice, such a difference cannot be accepted.
Yes, as long as the selected design is explained and justified. However, veterinary companies may elect to follow this guideline.
Where the guideline is followed, all aspects of the guideline should be followed. Finished product stability guidance does not address storage of bulk product during the manufacturing process.
The objective is to increase the transparency of the supporting data required and not to introduce any new regulatory requirements.
The data required will depend on the type of product and the activities performed i. The described framework is intended to cover all pharmaceutical bulk products.
However, it is understood that the requirements for some specific types of products e. The question most frequently arises in relation to solid oral dosage forms particularly tablet cores before coating or packaging but could be applicable at any stage in the manufacturing process of any pharmaceutical product where bulk is held in storage prior to further processing e.
In general, the level of information to be provided will be dependent on the nature of the bulk product.
The qualitative and quantitative if required composition of the bulk container should be described in the dossier and its control specification stated module 3.
It should be stated whether the bulk product is to be stored and if relevant, transported under controlled or non-controlled storage conditions.
According to the guideline on good distribution practice , the following should be taken into consideration:.
The maximum storage interval for the bulk product should be declared in the marketing-authorisation dossier, or alternatively, the maximum batch manufacturing time from start of product manufacture to completion of packaging in the final primary container for marketing.
When storage is prolonged i. The data to be provided will be dependent on results of development studies that represent the conditions proposed.
Unless provided in the dossier, these data should be verified in post-approval stability commitments on commercial scale batches.
Where transportation of bulk between manufacturing sites is proposed, the impact of excursions outside of the original storage conditions should be discussed and, where necessary, supported by accelerated stability data.
If other methods are proposed, these should be declared and justified through inclusion of batches that represent the full proposed holding intervals of the bulk product intermediate in the finished product stability programme.
Stability studies on bulk should reflect real storage conditions in the standard container foreseen at the manufacturing site.
In the event that more than one manufacturing site is involved, the stability studies should also cover any transportation duration and conditions.
If storage orientation has a significant effect on the delivered dose during these studies i. The preferred storage orientation should be detailed. As it cannot be guaranteed that the product will always be stored in the preferred orientation, the repriming instructions in the product information should be based on the worst-case scenario i.
According to European Union legislation, pharmaceutical manufacturers are required to use European Pharmacopoeial standard water in the manufacture of medicinal products.
Following discussions at the QWP and the ad hoc good-manufacturing-practice inspectors' group, it is suggested that the introduction of such methods might require specific review to ensure that the appropriate validation steps have been followed and that the water continues to meet the Ph.
Since, in the case of water, the validation will not be product specific, it is suggested that a company could request the supervisory authority to carry out a specific site inspection.
The performance of such an inspection would be at the discretion of the supervisory authority and could involve a pharmaceutical assessor where necessary.
Since it is expected that the water will continue to meet Ph. Skip to main content. Veterinary regulatory Overview Research and development Marketing authorisation Post-authorisation.
Human regulatory Overview Research and development Marketing authorisation Post-authorisation Herbal products. Quality of medicines questions and answers: Acceptability of two different appearances shape, dimensions, colour for a single strength tablet in a single Marketing Authorisation.
Appearance of tablets of different strengths. Design of in-use shelf life for solid oral dosage forms in multi-dose containers.
Expand all Collapse all. If only one multi-dose container will be needed for the treatment, the in-use studies should cover at least the length of the treatment.
The study should cover the worst case scenario in respect of the container closure system size. If more than one container is needed, one of the two bullet points below should be used for guidance.
If the treatment is of definite length and the content of one multi-dose container will not suffice, or if the treatment is continuous without a defined end, the studies should cover at least the time necessary to consume the content of two containers to accommodate a situation where the patient takes doses from two containers in parallel.
The study could be designed with a less than daily opening of the container. If no relevant change is observed in the in-use study after 6 months for a product in its immediate packaging, the study does not need to be continued and no in-use shelf life should be set.
A relevant change in this context is an observed change to a quality attribute that is trending toward an out of specification result.
Claims for in-use shelf-life for solid oral dosage forms in multi-dose containers. Examples The in-use stability studies show no relevant deterioration.
The applicant proposes an in-use shelf-life of x months, as this is the time covered by the in-use stability study. When no relevant deterioration is observed an in-use shelf-life is not necessary.
No claims should be made in the SPC and questions on the introduction of an in-use shelf-life should not be raised by the Authorities.
The in-use stability studies show out of specification results after y months and support stability over x months. The SPC makes a claim for an in-use shelf-life of x months.
In this example an in-use shelf-life of x months in the SPC would be warranted. The in-use stability studies show a trend for deterioration, although the values are all within specification.
The applicant proposes an in-use shelf-life of x months as this is the time covered by the in-use stability studies.
An assessment should be made on a case-by-case taking into account the intended use of the medicinal product see Question 2.
The assessment should be based on the overall stability of the drug product and the rate of degradation observed in the in-use studies.
An in-use shelf-life should be set if out of specification results are expected based on the observations made. Too short in-use studies, where the intended use of the medicinal product has not been taken into account, are not an acceptable justification for a short in-use shelf life.
When GMP certification is not available, certification that the sterilisation has been conducted and validated in accordance with the following ISO standards would be considered to provide an acceptable level of sterility assurance for the empty primary container: Guidance on the application of ISO ; I.
Guidance on Dosimetric Aspects. Dossier requirements The following details regarding the sterilisation of the packaging components should be included in the dossier: The sterilisation method and sterilisation cycle; Validation of the sterilisation cycle if the sterilisation cycle does not use the reference conditions stated in the Ph.
Where the component is a CE-marked Class Is sterile device e. Particles originated from the container closure system. The use of a specific filtration step for other purposes is not within the scope of this Q Where relevant, the issue of glass delamination should be addressed in sections 3.
Quality data requirements to demonstrate suitability of multidose containers for preservative free eye drops NEW October An explanation should be provided how the container throughout the in-use shelf life: Appropriately scaled cross-sectional drawings should be provided.
Each microbial challenge study should include appropriate positive and negative controls to demonstrate effectiveness of the challenge protocol and detection methodology Validation studies to demonstrate the suitability of the tests employed, microbial recovery and limits of detection should be reported, discussed and justified.
Microbiological stress testing should be conducted throughout the in-use shelf-life. The following should be considered: For container components necessary for each design feature and function: Reduced testing of starting materials.
Setting specifications for impurities in veterinary medicinal products. Lower limits for individual impurities e. It should be noted however, that individual impurities observed at levels greater than 0.
Specific type of products — Dry product inhalers. The product performance should be investigated under conditions to simulate use by patients.
Specific types of product - Graduation of measuring devices for liquid dosage forms. Attention should among others be paid to the following items: Attention should be paid to the following items: If possible, overdosing should be prevented.
If the risk of overdosing cannot be avoided, appropriate care should be taken in the design of the scale graduation to prevent overdosing; the physical characteristics of the liquid in relation to the measuring device.
The combination should assure accurate and precise dosing. Considerations can be for instance the needle diameter and the particle size of suspensions in injectables, the homogeneity resuspendability of suspensions and emulsions prior to and during the application of the measuring device, or residual amounts of liquid in the measuring device after administration of the dose to the patient.
Specific types of product - Need for in vitro dissolution studies with alcohol for modified-release oral products including opioid drug products.
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