Guidance for Presenting the SPC, Package Leaflet and Labeling ...

Guidance for Presenting the SPC,Package Leaflet and LabelingInformation for Veterinary ProductsVersion 1Drug SectorSaudi Food & Drug AuthorityKingdom of Saudi ArabiaPlease visit SFDA’s website at http://www.sfda.gov.sa/En/Drugfor the latest updatePage 2 of 59

Document ControlVersion Date Author(s) Comments1.0 8/03/2012Product Evaluation and StandardsSetting DepartmentDraftPage 3 of 59

Introduction:This guideline is adapted from the EMEA Notice to applicants veterinary medicinalproducts, volume 6C.The document is intended to guide the applicants on how to present the requiredinformation for:• Summary of Product Characteristics (SPC);• Package Leaflet;• Labeling.The SPC is the basis of information for veterinary professionals on how to use themedicinal product safely and effectively. Package Leaflet shall be drawn up in accordancewith the SPC.This guideline provides advice on the principles of presenting information. Applicantsshould maintain the integrity of each section of the document by only includinginformation in each section, which is relevant to the section heading. However, someissues may need to be addressed in more than one section and in such situations theindividual statements may cross refer to other sections when these contain relevantadditional information.When submitting a new application for registration, renewal or variation, the informationpresented by the applicant regarding the SPC, Package Leaflet and labeling must followthis guidance.Page 6 of 59

Summary of Product Characteristics (SPC)General considerations for the preparation of the SPCWhen preparing an SPC, it should be noted that the SPC is intended to provide detailedobjective information on the conditions of authorization of a veterinary medicinal product.The SPC is not a promotional document, nor is it intended to constitute a summary of theevaluation of the medicinal product by the SFDA.It follows that all the statements contained in the SPC must be justified by the contents ofthe application dossier which is submitted to the SFDA. Statements of a promotionalnature such as “xx is the treatment of choice for y” are not acceptable. Moreover,extraneous information such as the results of toxicity studies should not be included unlessnecessary to enable the practitioner to assess the benefits and risks of the use of theproduct in a particular case.Particular care should be taken to ensure that clear and unambiguous language is usedthroughout the SPC. Attention should be given to the clear definition of the scope of theindications, contraindications, precautions for use and warning statements to ensure thatthese clearly identify the groups or sub-groups of animals concerned.Applicants should maintain the integrity of each section of the document by onlyincluding information in each section, which is relevant to the section heading. However,some issues may need to be addressed in more than one section of the SPC (e.g.contraindications plus interactions). In such situations, the individual statements maycross-refer to other sections when these contain relevant additional information.A separate SPC should be completed per pharmaceutical form, including all strengths ofeach pharmaceutical form, if appropriate, and containing all pack-sizes related to thestrength(s) and pharmaceutical form concerned.Standard statements are given in the template which must be used whenever they areapplicable. If the applicant can justify the need to deviate from these statements toaccommodate product-specific requirements, alternative or additional statements will beconsidered on a case-by-case basis.Page 7 of 59

Bracketing convention:{text}: Information to be filled in.: Text to be selected or deleted as appropriate.A. SPC – For Pharmaceutical and Immunological Veterinary MedicinalProducts1. Name of the veterinary medicinal product{(Invented) name of veterinary medicinal product strength pharmaceutical form}Given in the following order: (invented) name (no ® symbols attached here orthroughout the text), strength (consistent with section 2 of the SPC), pharmaceuticalform “tablets” and “capsules” in the plural) and target animal species, if necessary , inorder to avoid any confusionE.g. {(Invented) name} 10 mg tablets for dogs{(Invented) name} 20 mg/ml solution for injection for dogsFor mock-ups and specimens, this information may be presented on different lines oftext or in different font sizes if necessary, provided that the appearance of the name ispreserved as an integrated item.When selecting invented names, care should be taken to avoid the use of words orabbreviations, which may give rise to confusion.In those sections of the SPC in which full information on the name of the medicinalproduct is specifically required, the name should include both the strength andpharmaceutical form, even if there is only one strength and/or pharmaceutical form.However, when otherwise referring to the medicinal product throughout the text of theSPC, strength and pharmaceutical form do not have to be mentioned in the name. TheInternational Non-proprietary Name (INN) or the usual common name of the activesubstance should be used when referring to properties of the active substance(s) ratherthan those of the product. The use of pronouns is encouraged where it improves thePage 8 of 59

Qualitative compositionThe international non-proprietary name (INN) recommended by the World HealthOrganization should be used, accompanied by its salt, derivative or hydrate form ifrelevant. If no INN exists, the Pharmacopoeial name should be used. If the substanceis not in the Pharmacopoeia, the usual common name should be used. In the absence ofa common name, the exact scientific designation should be given. Substances withoutan INN or an exact scientific designation should be described by a statement of howand from what they were prepared. References to a pharmacopoeial quality should notbe included.Where the active substance is present in the form of the parent molecule, the standardterminology should be used (e.g. dexamethasone).Where the active substance is present as a salt, derivative or hydrate, this should beclearly stated (e.g. dexamethasone acetate).For immunologicals, where the active substance is of a particular quality standard, forexample selected mutants or marker virus, this should be indicated. Excipients shouldbe referred to by their recommended INN if one exists or by their Pharmacopoeialname.Quantitative compositionThe quantity of the active substance must be expressed per dosage, per unit volume, orper unit of weight.Where the active substance is present in the form of a salt or hydrate, the quantitativecomposition should be expressed in terms of the mass (or biological activity inInternational (or other) Units where appropriate) of the active entity or entities (base,acid or anhydrous material) in the molecule (e.g. X mg levamisole as levamisolesulphate).However, in the cases of older compounds which have traditionally been expressed inthe form of a salt or hydrate, it may in some cases be appropriate to indicate thequantitative composition in terms of both the parent molecule and the salt (e.g. X mgPage 10 of 59

levamisole equivalent to Y mg levamisole sulfate)In the case of unit dose preparations, the quantitative composition should be stated perunit dose (e.g. X mg per tablet; Y mg per ampoule). In other cases, the quantitativecomposition should be stated in terms of mg per g or mg per ml. When the product is apowder to be reconstituted prior to administration, the quantity per ml afterreconstitution should be stated.For immunologicals, the biological activity, the titre or the potency of the activesubstance should be described in international or other units and expressed per dose. Ininactivated vaccines the titre before inactivation is not acceptable. The compositionshould be given in terms of minimum quantities per dose and, if appropriate withmaximum quantities per dose and an indication of the nature of a single dose (e.g. volume).Active substance:Full details of the qualitative and quantitative composition in terms of activesubstances should be provided. Expressed per dosage unit or according to the form ofadministration for a given volume or weight, using their INN or common names. Theuse of “%”, ppm or ppb as a strength should be avoided.]For salt/ester:E.g.:{quantity of active moiety} as {salt/ester}or{quantity of active moiety} equivalent to {quantity of salt/ester}5 mg {X} as {Y}8 mg {X} equivalent to 10 mg {Y}[E.g. Aluminum gels or salts, mineral or vegetable oil]Knowledge of which is essential for proper administration of the veterinary medicinalproduct, e.g . Preservatives such as formaldehyde or thiomersal.]Page 11 of 59

[For immunologicals, traces of antibiotics and/or other substances used in productionof vaccines not present in sufficient quantities to have a pharmacological effect shouldnot be included in the SPC]3. Pharmaceutical formThe term used in this section should be the same as the term used in section 1.[Include here a description of the visual appearance of the product pharmaceuticalform as marketed e.g. shape, texture, colour, imprint, including information on pH andosmolarity as required. In case of vaccines intended for reconstitution, the appearanceof the product before reconstitution should be stated here]Examples:-‘Tablet.White, circular flat bevelled-edge tablets marked ‘100’ on one side.’-“Solution for injection.Pale yellow, clear solution for injection, pH 7.0”If the product is not presented in the final pharmaceutical form intended foradministration to animals, the final pharmaceutical form should also be stated, e.g.“powder and solvent for solution for injection”.In case of tablets, designed with a score line, a statement should be given whether ornot reproducible halfing of the tablets has been shown.Examples:-“The tablets can be divided into equal halves”.-“The scoreline is intended to facilitate ease of swallowing and not to divide intoequal doses.”4. Clinical particulars4.1 Target species[Including any sub-category; indicate species in singular or plural]Page 12 of 59

4.2 Indications for use, specifying the target speciesThe indications should be clearly defined for the target species. It should be clearlystated whether the treatment is for prophylactic, therapeutic or diagnostic purposes.[For immunologicals, the indications should be clearly defined for the target speciesand should be substantiated by data in the dossier.The indications may be considered as the general claims for the immunologicalveterinary medicinal products. It gives the intention of the use of the immunologicalveterinary medicinal product. One or more of the following standard text and wordingshould be used, as appropriate.For active immunization or passive immunization of target species to:- Prevent mortality, clinical signs and/or lesions of the disease;- Prevent infection;- Reduce mortality, clinical signs and/or lesions of the disease;- Reduce infection.In addition to the indications, the onset and duration of immunity of theimmunological veterinary medicinal product should be specified, if appropriate.Where appropriate, further information on the protection that can be expected from theuse of the immunological veterinary medicinal product may be included.4.3 Contraindications[Do not specify species which are not included in the target species, unless studies orknowledge indicate severe toxicity; non-indications (e.g. “this veterinary medicinalproduct is not indicated for...”) should not be mentioned]Situations, which arise from a set of circumstances where the veterinary medicinalproduct must not be used for target animal safety reasons, i.e. absolutecontraindications, are the subject of this section. Contraindications may be linked witha target species or a sub-group of the target species, the administration of the productby a particular route or with administration in conjunction with other products.Furthermore, particular clinical diagnoses, concomitant diseases, age or sex mayPage 13 of 59

Information could include recommendations on the handling of animals, the properuse of the product or any other impact on the efficacy of the product.Additionally it is to warn prescribers of possibilities of modifications of the efficacyprofile of the product, which may arise in particular situations such as very old or veryyoung animals.Description should be made under which conditions the veterinary medicinal productmay be recommended for use in such groups provided the special precautions arefollowed. Situations in which use of the medicinal product is absolutelycontraindicated should be mentioned under section 4.3. only and is not to be repeatedin this section.Descriptions of warning and precautions regarding pregnancy, lactation or lay andother aspects of interactions should be dealt with in sections 4.7 and 4.8 respectively.Examples:- Limitations of use, if adequate:“Although the product may be safely administered to… with …, it has notherapeutic effect against …; or“The efficacy of … has not been established in dogs weighing less than … orunder …of age”.- Information about dose or duration:“A second injection must not be given, even if clinical signs recur…”.- General recommendations for the proper use and about handling, if appropriate:“Animals with acute infections and severely reduced feed intake should be treatedwith a suitable injection product first”.- Impact on efficacy:“Frequent shampooing or immersion of the animal in water after treatment mayreduce the efficacy of the product” or“Animals may be bathed xx hours after treatment without loss of efficacy”.Information on resistance should be included in this section, if applicable.Page 15 of 59

animals with renal or hepatic impairment (including the degree of impairment,such as mild, moderate or severe) or cardiac disease (including the severity of thecondition) or sensitive sub-populations e.g. ivermectin sensitive collies.Examples:- “Special care should be taken when administering the product to animals with, since ….”- “Treated animals should be monitored for …”- “ may occur when administering the product to , in this case treatments should be < discontinued or doseshould be reduced>.- Any measures which can be taken to identify animals at risk and to prevent theoccurrence, or to detect early the onset or worsening of conditions. Also, anysafety measures to minimize impact of the treatment to untreated animals shouldbe mentioned.- Where appropriate, information may also be provided about possible risksresulting from the off-label use of the product.Descriptions of warning and precautions regarding pregnancy and lactation and otheraspects of interactions should be dealt with in sections 4.7 (Use during pregnancy,lactation or lay) and 4.8 (Interactions) respectively.Descriptions on general information for instance on handling and directions for properuse concerning the mode of administration should be dealt with in section 4.9(Amounts to be administered) with cross reference to section 4.4 (Special warnings)e.g. “Do not administer more than 10 ml in each site of injection”.Do not use chlorinated water” for immunologicals.[Actions necessary to avoid pathogenic agents spreading from the vaccinate to eithernon-target categories of the same species or non-target species (for immunologicals.).]Page 17 of 59

{Species} and unvaccinated {species} in contact with vaccinated {species} mayreact to the vaccine strain, presenting clinical signs such as ….>[Any warnings necessary for excipients or residues from the manufacturing process.]ii. Special precautions to be taken by the person administering the medicinalproduct to animalsRisks resulting from the nature of the product, its preparation and use and of any risksresulting from the particular characteristics of the user should be stated here.Possible hypersensitivity reactions in the user to any of the excipients or residues fromthe manufacturing process should be included.Example:- People with known hypersensitivity to xx should If applicable, information should also be given for persons in close contact to thetreated animal e.g. animal owner, children, immuno-compromised persons, andpregnant women.Example:- Women of child-bearing potential should avoid contact with, or wear disposablegloves when administering, the product.Recommendations should be given to minimize the exposure of the user duringadministration or preparation of the product for administration.Page 18 of 59

Safety phrases given in international legislation should be used where possible.Guidance on action to be taken following accidental contact should also be given,where necessary..[If the product contains mineral oil:]Page 19 of 59

[Other precautions regarding impact on the environment, or chemical reactions ofthe product with furniture or clothes.]Examples:- This product is highly flammable. Keep away from heat, sparks, open flame orother sources of ignition.- Do not allow treated animals to swim in water courses until at least … hours/daysafter administration.[The following statements, which are relevant only for the product label and packageleaflet, should not be included in the SPC:‘For veterinary use only.’‘Keep out of reach and sight of children.’]4.6 Adverse reactions (frequency and seriousness)[By target species if more than one. Only include the adverse drug reactions (ADRs),which are those effects where a direct causal relationship between the effects and thetreatment has been established]This section should include information on adverse drug reactions attributed to theproduct when used as recommended. The reactions listed should be based on anassessment of all observed adverse events and all facts relevant to their causality,severity and frequency. The main adverse reactions in the target species should bePage 20 of 59

included in the SPC, if they are at least possibly causally related, based for example ontheir comparative incidence in clinical trials, or on findings from epidemiologicalstudies and/or on an evaluation of causality from individual reports. Adverse events,without at least a suspected causal relationship, should not be listed in the SPC. Datacan be derived either from data submitted in an application dossier or from postauthorizationpharmacovigilance reports.This section should also include information about any action that may be taken by theanimal owner or the veterinarian in case of adverse reactions, for example immediatecessation of treatment or emergency resuscitation. If there is a need for awareness ofclinical signs representing early warning of a serious adverse reaction, a statementshould be included. Any need for specific clinical or laboratory monitoring should bestated.Claims regarding the absence of specific adverse reactions, statements on lack of proofof causal association or comparative frequency statements other than those describedbelow should not be included in this section.In order to provide clear and readily accessed information, the section should bestructured according to the following recommendations:a) Description of the adverse reaction(s)The information in this section must be consistent with the figures presented andshould not contain general statements such as "well tolerated".The following information should be provided for each adverse reaction: a briefdescription of the nature of the reaction, the duration, reversibility and intensity ofthe reactions, the frequency of the reaction experienced in treated animals and anyeffect on the general state of health of the animal. In addition, it should beindicated whether certain species or breeds or types of individual are moresusceptible to the undesirable effect concerned, or whether it is more frequentunder certain types of husbandry conditions.All adverse reactions should be ranked in “frequency groupings” with the mostfrequently occurring reactions listed first, using the following convention:Page 21 of 59

Adverse reactionVery commonCommonUncommonRareVery rareIncidencemore than 1 in 10 animals displaying adverse reaction(s)during the course of one treatmentmore than 1 but less than 10 animals in 100 animalsmore than 1 but less than 10 animals in 1,000 animalsmore than 1 but less than 10 animals in 10,000 animalsless than 1 animal in 10,000 animals, including isolated reportsMore precise figures on the frequency of adverse reactions from clinical trials, e.g.XX% animals, are generally of limited value under conditions of market use andshould only be included when it is of particular relevance to the animal owner oruser of the product and/or prescriber to be informed of certain risks. In these casesit is preferable that the data should be based on pooled study results and/or largestudies performed under actual market conditions and should refer to adversereactions, not to unrelated adverse events.This information can be presented in tabular format. Examples of acceptablestatements are given below:- “Commonly reported adverse reactions are gastrointestinal signs such asdiarrhoea”.- “Adverse reactions are rare (

4.7 Use during pregnancy, lactation or layIn order to ensure the safe use of the product, the user must be informed of therecommendations regarding the use of the product in pregnant/lactating animals orlaying birds. Information about use of the product during pregnancy or lactation mayhave been provided in the sections dealing with contraindications or specialprecautions for use. In such cases, a cross-reference to the relevant section will besufficient. Information on the reasons for the relevant recommendation should alwaysbe given.In the absence of data, the use of this veterinary products is not recommended.In the case where reproductive toxicity studies have shown evidence of teratogenic,foetotoxic or maternotoxic effects in the target species or in other animal species, theapplicant should give further information.Examples< Can be used during pregnancy> (if the safety on pregnant animals has been shown inthe target species). because…” (if adversereactions have been shown during pregnancy with the recommended dose in the targetspecies, a case by case evaluation is needed and depending on the type of reaction).Page 23 of 59

The tolerance of the product in lactating animals and suckling off-spring should beaddressed here. Information in relation to consumer safety i.e. consequences of residuesfor the use of milk for human consumption should be given in section 4.11 (Withdrawalperiod).Where possible, information on excretion of the active substance and/or its metabolite(s)in milk should be given. Where relevant, recommendation as to whether to stop orcontinue to feed (new-born) animals with milk obtained from the mother should be given,and the reason for the recommendation should be stated.Examples: (If the safe consumption of milk obtained from treatedanimals has been shown in the off spring in the target animal)., because” or “New born calves.. should not befed with milk from the treated animals, because…” (If adverse reactions have been shownin the off spring consuming milk from treated animals).For chicken/avian products, it should be indicated if the product is unsuitable for layingbirds.Example:- “Do not use in breeding birds and/or within xx weeks before the onset of the layingperiod”.If the product is not for use in laying birds the prohibition of use is given in section4.4. Information about the consequences of residues for the use of eggs for humanconsumption should be given in section 4.11. Withdrawal period.Page 24 of 59

The following standard phrase should be used when applicable:“Do not use inbreeding animals”.Information regarding fertility in both males and females should be given in sections4.3 (Contraindications), 4.4 (Special warnings) or 4.6 (Adverse reactions), asappropriate.4.8 Interaction with other medicinal products and other forms of interaction [if appropriate] [if appropriate. For pharmaceuticals] [For immunologicals][Where safety and efficacy data are available for use of the products with others thefollowing statements are applicable:When the vaccines can be used on the same day:[For immunologicals][In the case of products administered parenterally, the products should be given atdifferent sites].When the vaccines can be used concurrently but not on the same day: [For immunologicals][The X number of days/weeks and the references to before or after are based on thedata presented by the applicant in the marketing authorization file. They correspond toPage 25 of 59

the minimum time between administrations for which compatibility data have beensubmitted].[In addition to the above statements, to reflect the absence of information on the safetyand efficacy of the association with any other vaccines, the following wording shouldalso be included:] [For immunologicals]4.9 Amount(s) to be administered and administration routeInclude information on the posology and method of administration. Posology: targetgroups to be specified, e.g. cattle less than 1 year of age. Method of administration:directions for proper use by healthcare professionals or by the farmer or owner andmixing instructions, if appropriate. Further practical details for the farmer or ownercan be included in the package leaflet or, in its absence, on the label.]The dosage has to be specified for each target species, route of administration andindication.The dosage should be given per kg bodyweight (BW) in the first place, whereappropriate, as well as in terms of the amount to be administered to the animal (e.g. mlor mg/xx kg BW).The dosage should be expressed in terms of a veterinary medicinal product (e.g. byunit doses or by a volume of solution administered to the animal). Whenever a titre isexpressed in terms of infectious dose the wording should be cell culture infectiousdose (CCID 50%) and egg infectious dose. Other terms can be added in order to guidefor proper use of the product. International System (SI) units should be used. Thefrequency/interval and duration of administration should be specified in hours, days,weeks or months. [For immunologicals].The method, including route and site of administration and directions for proper use bythe veterinarian, farmer or owner should be given. Any special equipment needed forPage 26 of 59

administration of the product should be mentioned. Where the product is to beadministered via the feed or water, any dosage adjustment for inappetent animalsshould be specified, if justified from the data available.Other terms can be added in order to provide guidance on the proper use of theproduct. International System (SI) units should be used. The frequency and duration oftreatment should be specified in hours, days or weeks.For products to be administered via drinking water, important additional informationshould be added here:- “Medicated drinking water should be refreshed or replaced every “xx” hours.”For premixes for medicated feeding stuff, clear instructions for the proper preparationof the medicated feed e.g. pelleting instructions and mixing equipment, and the amountof premix for the incorporation should be provided. Also, information on the feedingstuff(s) to be used should be included. If necessary, the use of a pre-mixture should berecommended.For products to be reconstituted, information on the solvent to use and its volumeshould be given.[In case of vaccines intended for reconstitution, a visual description of the reconstitutedvaccine should be included here, e.g.: ]4.10 Overdose (symptoms, emergency procedures, antidotes), if necessaryThe purpose of overdose studies is to detect signs of possible adverse reactions and toidentify the dose at which they occur, in order to establish a safety margin.Signs observed at higher dose levels than the recommended one should be mentioned.If no clinical signs were observed this should be mentioned as well. The followinginformation should be provided, if available:- Clinical signs, nature, evolution, seriousness, duration. It should also be indicatedat what doses the overdosage signs were observed.- Available symptomatic treatments.Page 27 of 59

- Emergency procedures.- Antidote(s).4.11 Withdrawal period(s)The withdrawal period is defined as the period between the last administration of theveterinary medicinal product to animals and the production of foodstuffs from suchanimals. Where all foodstuffs may be used for human consumption during thetreatment period and immediately after the last administration of a veterinarymedicinal product, a withdrawal of “zero days” should be indicated.If necessary, withdrawal periods should be stated for meat and offal, milk, or eggs.Withdrawal periods should be indicated in whole days, using Arabic numerals, exceptfor milk withdrawal periods, which may be more appropriately expressed in wholehours. A zero withdrawal period should be expressed as ‘Zero hours/days’.However, for fish, the withdrawal period should be stated in degree-days. The numberof degree-days is divided by the average water temperature, in °C, to give thewithdrawal period in days.When expressing the withdrawal period, the method of treatment must be taken intoaccount:- In the case of single administration only, the withdrawal period starts from thetime of treatment.- In the case of two or more administrations, the time of the last treatment is definedas the start of the withdrawal period.- If a product is removed at the end of the treatment (e.g. implants), the time of theremoval of the product is defined as the start of the withdrawal period.- In the case of intra-mammary products administered during the dry period, thewithdrawal period for animal slaughter for meat starts from the date of treatment;for milk the withdrawal period is determined by the date of subsequent calving.For veterinary medicinal products for food producing species, which containpharmacologically active substances without MRLs (e.g. for milk/eggs), relevantinformation should be given.Page 28 of 59

For a majority of immunological products the concern is in respect of live zoonoticorganisms, adjuvants and preservatives. It is not anticipated that animals will be likelyto be slaughtered for human consumption within a few days of being vaccinated, howeverthis possibility should be addressed if relevant.Examples:< Not applicable” (For non-food producing species). >< Zero days” (For food producing species where no withdrawal period is necessary). >< xx hours, days or degree-days” (For food producing species where a withdrawalperiod is necessary). >[for milk producing animals]< Do not use in pregnant animals, which are intended to produce milk for humanconsumption, within xx months of expected parturition (For milk food producinganimals species where no MRL exists for milk). > [forlaying birds]5. Pharmacological propertiesThe therapeutic group (according to the ATCvet classification system) and the ATCvetcode should be stated at the beginning of this section.5.1 Pharmacodynamic properties [not applicable for immunologicals]The pharmacodynamic activity of the active substance(s) should be specified, togetherwith the mechanism of the action, on the basis of the information contained in theapplication dossier. Also, information on resistance should be included in this section,if appropriate.5.2 Pharmacokinetic particulars [not applicable for immunologicals]Information, relevant for the proposed use of the product should be provided on thePage 29 of 59

absorption, distribution, biotransformation and elimination of the active substance ineach of the -target species, for example:Absorption- Percentage of the dose absorbed by the recommended route of administration, e.g.oral or dermal route;- Time necessary to obtain the maximum concentration (T max );- The maximum concentration (C max );- Influence of feeding regime for absorption by the oral route;- Quantity or percentage of the dose applied absorbed after topical administration.Distribution- Existence of possible linearity between the concentrations obtained and the doseadministered;- Degree of protein binding;- Tissue distribution;- Apparent volume of distribution.Biotransformation- Information relating to metabolism;- Activity of metabolites;- Percentage of the substance metabolized if known.Elimination- Half-life;- Principal routes of excretion. Also, if relevant from an environmental point ofview, information on secondary excretion routes might be included (e.g. mainexcretion route via urine; however, some active metabolites with impact on theenvironment might also be excreted via faeces).For products intended for multiple administrations information on kinetic propertiesafter repeated dosage should be given. Additionally, information on steady state levels,possible changes in absorption, distribution, metabolism and elimination between thepharmacokinetic particulars after a single administration and those after multipleadministrations should be taken into consideration.Page 30 of 59

Immunological properties [applicable for immunologicals]A brief description of the immunological properties, characteristics of the activesubstance(s) and the ATC vet code should be included in this section. For example:- To stimulate active immunity against (……).- To provide passive immunity against (……).- To affect the physiological function of through immunologicalmechanism(s).To modulate the function of the immune system of . [if not applicable delete this section]For products, which might enter the environment directly e.g. medicines for fish or viamanure, general information on environmental effects should be provided. The impactof the active substance or relevant metabolites excreted into the environment should beaddressed. Information on degradation and factors influencing this (e.g. light, pH,temperature) and other ways of deactivation (e.g. binding to organic matter) should begiven. Possible accumulation in the environment should be addressed.6. Pharmaceutical particulars6.1 List of excipients[Each excipient to be listed on a separate line according to the different parts of theproduct][A qualitative list (not quantitative) should be provided][Name of the excipient(s) in the language of the text]A list should be given of the excipients, expressed qualitatively only. All excipients,which are present in the product, even those present in small amounts, should beincluded. The active substance itself, residues of substances used during manufactureof the finished product (e.g. solvents or head-space gases), and lubricants for prefilledsyringes should not be included. Excipients that should usually be included on theproduct literature include preservatives, colorants and premix carriers.Excipients should be referred to by their recommended INN, if one exists,accompanied by the salt or hydrate form, if relevant, or by their Pharmacopoeial name.If an excipient has neither an INN nor a Pharmacopoeial name, it should be describedPage 31 of 59

y its usual common name. References to the pharmacopoeial quality should not beincluded.E numbers should be given where they exist if the excipient has a recognized action oreffect, for example preservatives and coloring matters, along with the common nameof the excipient.Flavors or fragrances may be declared in general terms (e.g. ‘orange flavor’, ‘citrusper-fume’). However, any of the components, which have a recognized action oreffect, must be included.Modified excipients should be declared in such a way as to avoid confusion with theunmodified excipients (e.g. pregelatinised starch).For clarity, it is recommended that each excipient be listed on a separate line and noabbreviations should be used.Ingredients that may or may not be added for pH-adjustment should be followed bythe parenthesis “(for pH adjustment)”.In the case of premixes for medicated feeding-stuffs, the main carriers in bracketsshould be indicated.6.2 Incompatibilities[Information should be given about major physical or chemical incompatibilities of theproduct with other products with which it is likely to be diluted, mixed or coadministered.Major incompatibilities observed from compatibility studies should beincluded here] [if incompatibility is not a concern due to the pharmaceutical formof the product, e.g. for solid oral pharmaceutical forms] [e.g. for parenterals, premixes formedicated feeding stuffs]Page 32 of 59

[It is not permitted to mix immunological products with other products, except othercomponents or the recommended diluent, unless compatibility data have beenprovided. In the absence of this data the following statement should be used][If applicant has demonstrated that mixing of products (simultaneous administration)is possible and if it is accepted by SFDA, the following statement should be used:]6.3 Shelf-lifeThis section should include:The shelf-life should be expressed in Arabic numerals as : In the case of multi-dose preparations presented in sealed containers, the shelf-life ofthe broached or opened container should also be stated. Similarly, in the case ofpremixes for medicated feeding-stuffs, the shelf-life should be indicated for thepremix. For medicated drinking water, the shelf life should be stated and may notexceed 24 hours.No storage conditions should be included here. They are given in section 6.4 (Specialprecautions for storage).6.4 Special precautions for storageThis section contains the information necessary for the correct storage of the product:temperature, light and humidity. If no storage warning is required, the followingphrase should be used .Page 33 of 59

Storage conditions for veterinary medicinal products should be made according to therecommended labeling statements, see Appendix 1.6.5 Nature and composition of immediate packaging[Include full information about contents of the packaging, such as type(s) of theimmediate and outer containers (e.g. glass vial in a cardboard box), material (e.g. glasstype, type of plastic) in contact with the veterinary medicinal product, package size(s)for the particular pharmaceutical form and strength(s), and devices supplied. Includethe fill-volume/weight of the container, if appropriate.All pack sizes must be listed. If more than 1 pack size applicable, add:] 6.6 Special precautions for the disposal of unused veterinary medicinal productor waste materials derived from the use of such products, [if any]This section should include information necessary for the safe disposal of unusedproduct, and the equipment used for the administration of the product to animals. Inaddition, reference should be made to any restrictions on the disposal of wasteproducts from treated animals.In particular cases there may be a need for specific warnings due to the environmentalfeatures of the active substance/metabolites, for example: [e.g. pharmaceuticals and inactivated immunologicals] [live immunologicals] [if applicable]Page 34 of 59

7. Marketing authorization holderName, address and contact details of the marketing authorization holder (includingelectronic mail address, if appropriate) should be included. However, references toweb-sites on the internet should not be included.{Name and address}8. Marketing authorization number(s)[Item to be completed by the Marketing Authorisation Holder once the MarketingAuthorisation has been granted.]9. Date of first authorization / renewal of the authorization[Item to be completed by the Marketing Authorisation Holder once the MarketingAuthorisation has been granted or renewed.]The date of first authorization and the date of renewal, if applicable, should beindicated.Date of first authorization Date of renewal 10. Date of revision of the textLeave blank in case of a first authorization. In case of changes to the SPC, the date ofapproval by the SFDA should be indicated.{MM/YYYY}Page 35 of 59

Package Leaflet - For Veterinary Medicinal Products[NOTE: the inclusion of a package leaflet in the packaging of veterinary medicinalproducts shall be obligatory unless all the information required can be conveyed on thecontainer and the outer package].The applicant should provide package leaflet by both arabic and english languages. Aseparate package leaflet should be provided per strength and per pharmaceutical form. Thepackage leaflet must be easily readable for the healthcare professionals, farmer or animalowner.It is important that the package leaflet can easily be tracked for updates and review. Eachpackage leaflet should be given a reference number along with the date the leaflet wasissued and a suitable review date. Each package leaflet should be reviewed every 5 yearsor when necessary.The following items must appear in the package leaflet as required by this guidance. Inexceptional cases, alternative headings may be acceptable. This should not in any caseaffect the content required for the section concerned. Applicants should justify the use ofalternative headings. For certain products not all items may be relevant, in this case thecorresponding heading should not be included.Bracketing convention:{text}: Information to be filled in.: Text to be selected or deleted as appropriate.Page 36 of 59

Package leaflet for:{(Invented) name of veterinary medicinal product strength pharmaceutical form} [as it appears in the SPC under section 1.]1. Name and address of the marketing authorization holderName, address and contact details of the marketing authorization holder (Including town,postal code (if available) and country name (Telephone, fax numbers, email addressesmay be included (no websites or e-mails linking to websites allowed).

• Information on the appearance of the product before reconstitution/dilution, ifapplicable.4. Indication(s)This section should include:• Clearly defined indications for the target species.• A short section describing the benefits of the product and the purpose of thetreatment.5. ContraindicationsThis section should include information under section 4.3 of the SPC, if appropriate.6. Adverse reactionsThis section should include information on adverse drug reactions attributed to theproduct when used as recommended. The reactions listed should be based on anassessment of all observed adverse events and all facts relevant to their causality,severity and frequency.This section should also include information about any action that may be taken by theanimal owner or the veterinarian in case of adverse reactions, for example immediatecessation of treatment or emergency resuscitation.7. Target speciesThe target species, and sub-categories, when appropriate, should be indicated.Dosage for each species, route(s) and method of administration.8. Dosage for each species, route(s) and method of administrationThe dosage should be given per kg bodyweight (BW) in the first place, whereappropriate, as well as in terms of the amount to be administered to each species (e.g.ml or mg /xx kg BW).Page 38 of 59

The method, route and site of administration of the veterinary medicinal productshould be given.[Method of administration: directions for proper use of the veterinary medicinalproduct; e.g. “Shake well before use”.]9. Advice on correct administration[Directions for proper use by healthcare professionals, farmer or animal owner;including practical details such as mixing instructions. A description of appearanceafter reconstitution, if applicable]10. Withdrawal periodThis section should include information under section 4.11 of the SPC.11. Special storage precautionsThis section should include:- Keep out of the reach and sight of children.- A statement of the recommended labeling statements (see Appendix 1).Note: storage conditions in Arabic language should be added.- Shelf-life of the veterinary medicinal product as packaged for sale.- Shelf-life after first opening of the immediate packaging (where relevant).- Shelf-life after dilution or reconstitution (where relevant).- Shelf life after incorporation into feed (where relevant).- Use immediately, do not store (where relevant).- Warning against certain visible signs of deterioration (where relevant).e.g. 12. Special warning(s)This section should include warnings from relevant sections 4.4, 4.5, 4.7, 4.8, 4.10 or6.2 from the SPC should be included as appropriate in user-friendly wording.Page 39 of 59

13. Special precautions for the disposal of unused product or waste materials, ifanyThis section should include information from section 6.6 of the SPC in user-friendlywording.e.g. 14. Date on which the package leaflet was last approvedLeave blank in case of a first authorization. In case of changes to the package leaflet,the date of approval by the SFDA should be indicated.{MM/YYYY}15. < Other information>This section should include:- Package size(s). All pack sizes should be listed. If appropriate, a standardstatement, ‘Not all pack sizes may be marketed’, should be included.- To report any side effect(s):− National Pharmacovigilance Center (NPC)o Fax: +966-1-2057662o E-mail: npc.drug@sfda.gov.sao Website: www.sfda.gov.sa/npcPage 40 of 59

LabelingThe data should be presented according to the template below, irrespectively of theirsequence on the actual labeling and their position and possible repetition on the individualsides/flaps of the packaging (e.g. top flap, front, back etc.).A separate text for the labeling of the outer and immediate packaging should be provided.Separate labeling documents should be prepared for each strength and pharmaceuticalform. However, different pack sizes of the same strength can be presented in onedocument. Where the same text for outer and immediate packaging is used, this should beclearly indicated in the heading.Standard statements are given in the template, which must be used whenever they areapplicable. If the applicant needs to deviate from these statements to accommodateproduct-specific requirements, alternative or additional statements will be considered on acase-by-case basis.Boxed headings are provided to help applicants when completing the template. However,they are not to appear in the final printed packaging materials (mock-ups/specimens).Bracketing convention:{text}:Information to be filled in.:Text to be selected or deleted as appropriate.Page 41 of 59

1. Requirments to appear on the < immediate packaging>a.Name of the veterinary medicinal product{(Invented) name of the product Strength Pharmaceutical form }{active substance(s)}[Name of the veterinary medicinal product, followed by its strength and pharmaceuticalform. The common name shall appear if the medicinal product contains only one activesubstance and its name is an invented name, as it appears in the SPC under section 1.]• Note: The invented (trade) name in Arabic language should be added.b. Statement of active and other substance(s)Expressed qualitatively and quantitatively per dosage unit or according to the form ofadministration for a given volume or weight, using the common names. Where the activesubstance is present as a salt, this should be clearly indicated.e.g.: “mg X” or “mg Y-hydrochloride (equivalent to mg Y)”.Express qualitatively those excipients known to have a recognized action or effect.However, where justified for space considerations, abbreviations for excipient namesmay appear on the labeling, on condition that these abbreviations together with the fullname are also included in section (6.1) of the SPC and section (3) of the package leaflet.c. Pharmaceutical formThe pharmaceutical form has to be mentioned on the outer package.d. Package SizeContents by weight, by volume or by number of doses of the veterinary medicinalproduct (i.e. content of bottle; pack size, including a reference to any ancillary itemsincluded in the pack such as needles, swabs etc…).In case of a combined labeling text covering different pack-sizes of the same strength,further pack-size(s) should be included in grey shading.e.g.28 tablets56 tabletsPage 42 of 59

e. Target speciesThe target species should be mentioned if not already included in the name.In addition to the wording, a pictogram can be used.f. Indication(s)Information to be included for immunologicals only.In case of space restriction and if the indication is clear from the name of the product, theindication should not be repeated.g.Method and route(s) of administrationThis section should include information on directions for proper use of the veterinarymedicinal product (e.g. “shake well before use”).In all cases, and especially if full details cannot be included on the outer packaging itself,a reference to the package leaflet must be included (read the package leaflet before use).h. Withdrawal period[Withdrawal period for veterinary medicinal products to be administered to foodproducingspecies ,for all the species concerned and for the various foodstuffs concerned(meat and offal, eggs, milk ,honey), including those for which the withdrawal period iszero][Not applicable for non-food producing animals.Present by species and/or food components.][as in SPC]i. Special warning(s), if necessary[Indicate any particulars essential for safety or health protection, including any specialprecautions relating to use and any other warnings.] [Unless already included under method androute(s) of administration or in case of space limitation.][For certain products e.g. injectables containing mineral oil or live vaccines, thefollowing statement should be included:]Page 43 of 59

is dangerous – see packageleaflet before use>j. Manufacturing and Expiry datesDates should be expressed with the month given as 2 digits or 3 characters and the yearas 4 digits, e.g.: 02/2010, Feb 2010.Where applicable, the shelf life after reconstitution, dilution or after first opening thecontainer should be included.k. Special storage conditionsThis section should include a statement of the recommended labeling statements (seeAppendix 1).• Note: Storage conditions in Arabic language should be added.l. Specific precautions for the disposal of unused products or waste materials, if anyThis section is not required on the immediate label and should include information fromsection 6.6 of the SPC in user-friendly wording, e.g. or .m. The words “veterinary use only” and the general classification for supply, ifapplicableThis section should include the following phrases, if applicable:- this phrase should be written in RED color.• n. The words “keep out of the reach and sight of children”This section should include the following phrase “keep out of the reach and sight ofchildren”. However, this section is not required on the immediate label.o.Name and address of the marketing authorisation holderThis section should include the town, postal code (if available) and country name of thePage 44 of 59

marketing authorization holder (telephone, fax numbers or e-mail addresses may beincluded).{Name and address}p. Marketing authorization number(s)[Item to be completed by the Marketing Authorisation Holder once the MarketingAuthorisation has been granted.]q. Name and address of the Agent in K.S.A (If any)This section should include telephone, fax numbers (e-mail addresses may be included) of theagent{Name and address}r. Manufacturer’s batch number {number}2. Minimum requirments to appear on small immediate packaging unitsAmpoules, small single-dose containers other than ampoules.On a case-by-case basis, the minimum particulars could be considered for containerswhere it is not feasible to include all the information. Such exceptional cases have tobe justified, discussed and agreed with the SFDA. In case where the space is notenough to hold the minimum requirments , the information should be provided as afolded label.a. Name of the veterinary medicinal product{(Invented) name of the product Strength Pharmaceutical form

species>}{active substance(s)}A clear pictogram of the target animal species might be used to replace mentioningthe target species on the packaging (to be discussed case-by-case).b. Quantity of the active substance(s)The active substance(s) should be expressed qualitatively and quantitatively.c. Contents by weight, by volume or by number of dosesd. Route(s) of administratione. Withdrawal periodf. Batch number {number}g. Manufacturing and Expiry datesDates should be expressed with the month given as 2 digits or 3 characters and theyear as 4 digits, e.g.: 02/2010, Feb 2010.Where applicable, the shelf life after reconstitution, dilution or after first openingthe container should be included.h. The words “veterinary use only”“veterinary use only” > this phrase should be written in RED color.Page 46 of 59

3. Minimum requirments to appear on blisters or stripsa. Name of the veterinary medicinal product{(Invented) name of the product Strength Pharmaceutical form }{active substance(s)}b. Name of the marketing authorization holder{Name} [Full/short name of the Marketing Authorization Holder]c. Manufacturing and Expiry datesDates should be expressed with the month given as 2 digits or 3 characters and theyear as 4 digits, e.g.: 02/2010, Feb 2010.d. Batch number {number}e. The words “for veterinary use only”“veterinary use only” > this phrase should be written in RED color.Page 47 of 59

Appendix 1: Recommended labeling statements• The statements that should be used if supported by the stability studies for finishedpharmaceutical products (FPPs) are listed in Table 1.Table 1: Recommended labeling statements for finished pharmaceutical products (FPPs)Testing condition under which the stabilityof the FPP has been demonstrated30 °C/65% RH (long-term)40 °C/75% RH (accelerated)Recommended labeling statement“Do not store above 30 °C” *5 °C ± 3 °C ”Store in a refrigerator (2 °C to 8 °C)”-20 °C ± 5 °C “Store in freezer”*“Protect from moisture” should be added as applicable.• Additional labeling statements that could be used in cases where the result of thestability testing demonstrates limiting factors are listed in Table 2.Table 2: Additional labeling statements for use where the result of the stability testingdemonstrates limiting factorsLimiting factorsFPPs that cannot tolerate refrigerationFPPs that cannot tolerate freezingLight-sensitive FPPsFPPs that cannot tolerate excessive heat, e.g.suppositoriesHygroscopic FPPsAdditional labeling statements, whererelevant“Do not refrigerate or freeze” a“Do not freeze” a“Protect from light”“Store and transport not above 30 °C”“Store in dry condition”Page 48 of 59

Appendix 2: Additional information that are required to be translatedinto Arabic languageA. Information on the outer package (in addition to the information that is provided in theguidance):1. Name of the veterinary medicinal product and strength2. Special storage condition.3. Only for veterinary use (this phrase should be written in red color).B. Blister information (in addition to the information that is provided in the guidance):1. Name of the veterinary medicinal product and strength2. Only for veterinary use (this phrase should be written in red color).C. Information on the outer package of small containers (less than 100 mL) (in addition tothe information that is provided in the guidance):1. Name of the veterinary medicinal product and strength2. Special storage condition.3. Only for veterinary use (this phrase should be written in RED COLOR).Page 49 of 59

Appendix 3: Readability of the label and package leafletIntroductionThe main purpose of this document is to provide guidance on how to ensure that theinformation on the labelling and package leaflet is accessible to and can be understood byusers.This document is written to assist applicants and marketing authorizations holders whendrawing up the labeling and package leaflet and preparing the mock-ups or specimens ofthe sales presentations.A. Recommendations for the package leafletGeneral considerationsThe package leaflet is intended for the user. If the package leaflet is well designed andclearly worded, this maximizes the number of people who can use the information.Companies are encouraged to seek advice from specialists in information design whendevising their house style for the package leaflet to ensure that the design facilitatesnavigation and access to information.The following guidance sets out recommendations on various aspects related to thepreparation of package leaflets. It is aimed at helping applicants/marketing authorizationholders to fully comply with the legal requirements and is based on experience where ithas been shown that using these techniques optimizes the usability of the package leaflet.1. Type size and fontChoose a font which is easy to read. Stylized fonts which are difficult to read should notbe used. It is important to choose a font in which similar letters/numbers, such as “i”, “l”and “1” can be easily distinguished from each other. The type size should be as large aspossible to aid readers. A type size of 9 points, as measured in font ‘Times New Roman’,not narrowed, with a space between lines of at least 3 mm, should be considered as aminimum.Consideration should be given to using different text sizes to enable key information tostand out and to facilitate navigation in the text (e.g., for headings).Page 50 of 59

The widespread use of capitals should not be used. The brain recognizes words in writtendocuments by the word shape, so choose lower case text for large blocks of text. However,capitals may be useful for emphasis.Do not use italics and underlining as they make it more difficult for the reader torecognize the word-shape. Italics, however, may be considered when using Latin terms.2. Design and layout of the informationThe use of “justified” text (that is text aligned to both left hand and right hand margins)should in principle not be used.Line spaces should be kept clear. The space between lines is an important factorinfluencing the clarity of the text. As a general rule the space between one line and thenext should be at least 1.5 times the space between words on a line, where practical.Contrast between the text and the background is important. Factors like paper weight,color of the paper, size and weight of the type, color of the type and the paper itself shouldbe considered. Too little contrast between the text and the background adversely affectsthe accessibility of the information. Therefore, background images should in principle notbe placed behind the text since they may interfere with the clarity of the informationmaking it harder to read.A column format for the text can help the reader navigate the information. The marginbetween the columns should be large enough to adequately separate the text. If space islimited a vertical line to separate the text may be used. Related information should be kepttogether so the text flows easily from one column to the next. Consideration should begiven to using a landscape layout which can be helpful to users. Where a multi-lingualpackage leaflet is proposed there should be a clear demarcation between the differentlanguages used; all the information provided in each language should be assembled.3. HeadingsHeadings are important and can help users navigate the text if used well. Therefore, boldtype face for the heading or a different color, may help make this information stand out.The spacing above and below the headings should be consistently applied throughout theleaflet. Same level headings should appear consistently (numbering, bulleting, color,Page 51 of 59

indentation, font and size) to aid the reader.The use of multiple levels of headings should be considered carefully, as more than twolevels may make it difficult for readers to find their way around the leaflet. However,where complex information has to be communicated multiple levels of headings may beneeded.Using lines to separate the different sections within the text can also be helpful as anavigational tool.4. Print colorAccessibility is not only determined by print size. Characters may be printed in one orseveral colors allowing them to be clearly distinguished from the background. A differenttype size or color is one way of making headings or other important information clearlyrecognizable.The relationship between the colors used is as important as the colors themselves. As ageneral rule dark text should be printed on a light background. But there may be occasionswhen reverse type (light text on a dark background) could be considered to highlight forinstance particular warnings. In such circumstances the quality of the print will needcareful consideration and may require the use of a larger type size or bold text. Similarcolors should not be used for the text and background as legibility is impaired.5. SyntaxSome people may have poor reading skills, and some may have poor health literacy. Aimto use simple words of few syllables.Long sentences should not be used. It is better to use a couple of sentences rather than onelonger sentence, especially for new information.Long paragraphs can confuse readers, particularly where lists of side effects are included.The use of bullet points for such lists is considered more appropriate. Where possible, nomore than five or six bullet points in a list are recommended.When setting out the side effects it is particularly important to consider the order in whichthey are given so the users may maximize the use of the information. In general, settingPage 52 of 59

out the side effects by frequency of occurrence, starting with the highest frequency, isrecommended to help communicate the level of risk to individuals. Frequency termsshould be explained in a way users can understand – for example “very common” (morethan 1 in 10 animals). However, where a serious side effect exists which would require theuser to take urgent action this should be afforded greater prominence and appear at thestart of the section. Setting side effects by organ/system/class is not recommended sinceusers are in general not familiar with these classifications.6. StyleWhen writing, an active style should be used, instead of passive. For example:-'take 2 tablets' instead of '2 tablet should be taken','-'you must....' is better than 'it is necessary ...'When telling users what action to take, reasons should be provided. Instructions shouldcome first, followed by the reasoning.“This medicine,…etc.” should be used rather than repeating the name of the product, aslong as the context makes clear what is being referred to.Abbreviations and acronyms should not usually be used unless these are appropriate.When first used in the text, the meaning should be spelled out in full. Similarly scientificsymbols (e.g. > or

Glossy paper reflects light making the information difficult to read, so the use of uncoatedpaper should be considered.Make sure that when the package leaflet is folded the creases do not interfere with thereadability of the information.8. Use of symbols and pictogramsThe images, pictograms and other graphics can be used to aid comprehension of theinformation, but these exclude any element of a promotional nature. Symbols andpictograms can be useful provided the meaning of the symbol is clear and the size of thegraphic makes it easily legible. They should only be used to aid navigation, clarify orhighlight certain aspects of the text and should not replace the actual text. Evidence maybe required to ensure that their meaning is generally understood and not misleading orconfusing. If there is any doubt about the meaning of a particular pictogram it will beconsidered inappropriate.Page 54 of 59

B. Recommendations for the labelingGeneral considerationsLabeling covers both outer packaging and inner packaging. Although inner packagingmay include a lesser set of particulars, many of the principles outlined in relation to outerpackaging will apply equally to the labeling of blister packs or other small package units.Labeling ensures that the critical information necessary for the safe use of the medicine islegible, easily accessible and that users of medicines are assisted in assimilating thisinformation so that confusion and error are minimized.Those involved in the design of labeling should consider the following sections prior tosubmission to the SFDA. The recommendations given in relation to the package leaflet(section A) may be applicable to labeling and should be borne in mind in designing andlaying out the required information on labels. The particulars appearing on the label of allmedicinal products should be printed in characters of at least 7 points (or of a size wherethe lower case "x" is at least 1.4 mm in height), leaving a space between lines of at least 3mm.In particular the information presented on small packs will need careful consideration sothat the text is presented in as large a type size as possible to reduce the likelihood ofmedication error.1. Name of the medicineThe full name of the medicinal product, with its strength and its pharmaceutical form, andthe target species should appear on the outer packaging and on the immediate packagingto aid accurate identification of the medicinal product.Where the medicinal product contains up to three active ingredients, the international nonproprietaryname (INN)/common name(s) of these active ingredient(s) should be statedafter the full name on the outer packaging and the immediate packaging, unless theINN/common name(s) is part of the name. The INN should be afforded due prominencefor safety reasons.2. Strength and total contentPage 55 of 59

Different strengths of the same medicinal product should be expressed in the samemanner: for example 250 mg, 500 mg, 750 mg, 1000 mg and NOT 1 g. Trailing zerosshould not appear (2.5 mg and NOT 2.50 mg). The use of decimal points (or comma)should be avoided where these can be removed (i.e. 250 mg is acceptable whereas 0.25 gis not). For safety reasons it is important that micrograms is spelt out in full and notabbreviated. However, in certain instances where this poses a practical problem whichcannot be solved by using a smaller type size then abbreviated forms may be used, ifjustified and if there are no safety concerns.3. Route(s) of administrationThis should be as stated in the summary of product characteristics (SPC). Negativestatements should not be used: for example “Not for intravenous use”. In principle onlystandard abbreviations may be acceptable (i.v., i.m., s.c.).Other nonstandard routes of administration should be spelled out in full. Some routes ofadministration will be unfamiliar to users and may need to be explained within thepackage leaflet.4. Design and layoutApplicants and marketing authorization holders should make best use of the spaceavailable to ensure that the important information is clearly mentioned on prime spaces onthe outer and immediate packaging, presented in a sufficiently large type size. Companylogos and pictograms may be presented, where space permits, on the outer packaging andon immediate packaging, provided they do not interfere with the legibility of themandatory information.Use of a large type size will be appropriate, although other factors may also be importantin making the information legible. Consideration should be given to the line-spacing anduse of white space to enhance the legibility of the information provided. For some smallpacks it may not be possible to present all the critical information in the same field ofview. The use of any innovative technique in packaging design to aid in the identificationand selection of the medicinal product is encouraged. It is also encouraged where space isat a premium.Page 56 of 59

Colors should be chosen to ensure a good contrast between the text and the background toassure maximum legibility and accessibility of the information. Highly glossy, metallic orreflective packaging should be avoided, as this affects the legibility of the information.Different colors in the name of the product are discouraged since they may negativelyimpact on the correct identification of the product name. The use of different colors todistinguish different strengths is strongly recommended.Similarity in packaging which contributes to medication error can be reduced by thejudicious use of color on the pack. The number of colors used on packs will need carefulconsideration as too many colors could confuse. Where color is used on the outer pack it isrecommended that it is carried onto primary packaging to aid identification of themedicine.Where a multi-lingual outer and/or immediate packaging is proposed there should be aclear demarcation between different languages where space permits.5. Blister pack presentationsFor blister pack presentations it is important that the particulars remain available to theuser up to the point at which the last dose is removed. Often it will not be possible toapply all the information over each blister pocket, consequently where a random displayof the information is proposed it should frequently appear across the pack. In all cases itwill be acceptable to apply the batch number, manufacturing and expiry dates to the end ofthe blister strip. If technically possible, applying this information to both ends of each stripshould be considered.In addition, blister foils should be printed to ensure maximum legibility of the informationusing a sufficiently large font.Color for the text and the font style, should be chosen carefully as the legibility of the texton the foil is already impaired due to the nature of the material. Where possible, nonreflectivematerial or colored foils should be considered to enhance the readability of theinformation presented and the correct identification of the medicine.Small containersWhere the labeling particulars cannot be applied in full to the labeling of small containers,Page 57 of 59

the minimum particulars could be considered. Other factors may need to be taken intoaccount such as the amount of information which has to be included and the font sizenecessary to ensure the legibility of the information.The criteria for small container statuswould normally apply to containers of nominal capacity of 100 ml or less.Innovative pack design is encouraged where space is at a premium (e.g. the use of wraparoundor concertina labels). Paper labels are recommended to increase the legibility of theinformation applied to, for example, ampoules.Page 58 of 59

References• Guideline on preparation of Summary of Product Characteristics SPC -Pharmaceuticals for veterinary medicinal products (revision 2 - 07/2006).• Guideline on preparation of Summary of Product Characteristics SPC -Immunologicals for veterinary medicinal products (revision 3 - 06/2007).• Annex III: labelling and package leaflet, European Commission, Version 7.3,2010.• Guideline on the readability of the label and package leaflet of medicinal productsfor human use, European Commission, 12 January 2009.Page 59 of 59