Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals

Transcription

1 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals

2 Código Spanish Español Code of Buenas Good Practices Prácticas for the Promotion de Promoción of Medicines de and Medicamentos Interaction y de Interrelación with de la Healthcare Industria Farmacéutica con los Profesionales Professionals1 Sanitarios1

3 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals1 Introduction... 3 Definition and purpose of the Code... 4 Scope of the Code... 4 Provisions of the Code Marketing authorization Information to be made available Information and its rationale Aceptability of material Transparency of promotion Use of reference quotations Distribution of promotional material Promotion via the internet Scientific service and review of promotional material Incentives Hospitality and meetings Pharmaceutical company staff Samples Studies Donations and grants Services rendered by entities integrated by healthcare professionals Services provided by healthcare professionals Rules of application of the code Request for queries Control of code compliance Infringements and sanctions Implementation guides and collaboration agreements Disclosure and compilation of rulings Entry into force of the code... 21

4 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals Introduction In 1991, Farmaindustria, conscious of the importance of providing accurate, fair and objective information about medicinal products to allow taking rational decisions on their use, adopted as Spanish Code the European Code of Practice of the Promotion of Medicines approved by the European Federation of Pharmaceutical Industries and Associations (EFPIA). Subsequently, in 1992, the Spanish Code was appropriately adapted to make it fully consistent with the provisions introduced by Directive 92/28/ECC of 31 March 1992 on the advertising of medicinal products for human use. The revised version of the Code took effect on January 1, On March 2002, FARMAINDUSTRIA s General Assembly approved a much more stringent and precise new version of the Code, and on January 2004 additional measures were taken to reinforce this self-regulation system on promotion of medicinal products by (i) preparing and approving implementation guides, (ii) implementing the query system, published in a question and answer format, and (iii) making an in-depth reform of the Rules of Procedure, including the start-up of the Code of Practice Surveillance Unit as the body responsible for active monitoring of Code compliance. A new version of the Code, of the Rules of Procedure for the Control Bodies of the Spanish Code and of the Implementation Guides which came into force in June 2005, and incorporated elements of the new version of the European Code approved in November 2004, and strengthened the self-regulation system. Subsequently, following approval of a new version of the European Code in October 2007, adapting the Spanish Code had become necessary, culminating in the approval of a new text on 26 June The recent amendment of Law 3/1991, of 10 January, of Unfair Competition, made by Law 29/2009 is of great importance, insofar as it promotes preparing Codes of Conduct by companies, associations, or commercial organizations, professionals and consumers in accordance with the provisions of Article 37. The self-regulation system for the promotion of medicines of the pharmaceutical industry fully complies with the provisions of the Law of Unfair Competition. It collaborates with and belongs to Autocontrol, which is entrusted with the resolution of controversies, Autocontrol being the only Spanish private agency attached to the EJE-Net (European Extra-judicial Network) of the Commission. Given the foregoing, resulting from the need to adapt the Code to applicable legislation to this issue and from pharmaceutical companies continuous commitment to provide selfregulation system with the higher level of credibility and transparency arises this new version of the Code, approved by the General Assembly of FARMAINDUSTRIA, during its meeting held on October 26th,

5 Definition and purpose of the code This Code represents the ethical rules which, using its self-regulation power and according to the provisions of article 97, paragraph 5 of Directive 2001/83/EC, on the Community code relating to medicinal products for human use, FARMAINDUSTRIA has agreed to comply as regards promotion of medicines for human use as well as with regards in the field of interactions with the healthcare professionals, with the desire to guarantee that both are carried out in the respect of the strictest ethical principles of professionalism and responsibility. For this purpose, an Agreement was signed with the Association for Self-regulation of Commercial Communication (Autocontrol). Compliance with the principles contained in the Code will ensure that the information made available to healthcare professionals when promoting the medicines they prescribe or supply is complete, up-to-date and accurate. This will be beneficial to the interests of both the Health Administration and the pharmaceutical industry, and to protect and improve public health. Both the content and nature of promotional activities or materials as well as the interaction with the healthcare professionals must contribute to strengthening confidence in the pharmaceutical industry. or under its control subsidiaries, foundations, associations, institutes, agencies, etc.- designed to directly or indirectly promote the prescription, dispensing, sale or consumption of its medicines. To the effects of this Code, without prejudice to what is established by the current legislation in this matter, any member of the medical, dentist related, pharmaceutical or nursing profession, or any other person who, in the practice of his/her professional activity, can carry out or determine the activities of prescribing, buying, distributing, dispensing or administrating a medicine, will be considered a healthcare professional. The Code covers all promotional methods, including journal and direct mail advertising, the activities of medical representatives, the sponsorship of scientific congresses and scientific or professional meetings attended by health care professionals, the Internet, the use of audiovisual systems such as films, video recordings, data storage systems, and others that could arise in the future, and the provision of samples, gifts and hospitality. Likewise, the Code covers all the forms of interaction between the Pharmaceutical companies and healthcare professionals, as well the ones derived from research agreements (clinical trials, studies) and other types of agreements (collaboration, Consulting, etc.). 4 Scope of the code The Code covers all the forms of promotion of medicines and interactions between the Pharmaceutical companies and the healthcare professionals or any other person who, in the practice of his/her professional activity, may carry out or determine the activities of prescribing, buying, distributing, dispensing or administrating a medicine. The term promotion refers to any activity undertaken, organized, or sponsored by a pharmaceutical company This Code is not intended to inhibit the exchange of medical and scientific information during the development phase of a product nor to limit the relationship between the pharmaceutical companies and the healthcare professionals, but to establish rules of conduct that the entire pharmaceutical industry agrees to adhere to. The Code does not cover: I) The labeling of medicinal products and accompanying package leaflets. II) Correspondence, possibly accompanied by material of a non-promotional nature

6 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals (e.g. scientific articles), needed to answer a specific question about a particular medicinal product, but only if it relates solely to the subject matter of the enquiry, is accurate and not misleading. III) Specific information and reference material relating, for example, to pack changes, warnings on adverse reactions in the setting of drug surveillance, trade catalogues and price lists, provided they include no information on the medicinal product. It also does not cover the information that the doctor may provide to a patient regarding certain medicines which, due to the complexity of their dosage, route of administration, etc., require the provision of additional information, as long as this information is intended to improve compliance with treatment. IV) Information on human health or diseases provided there is no reference, even indirect, to specific medicinal products. V) Corporate advertising of pharmaceutical companies. except as stated in article VI) Promotion of non-prescription medicinal products, except as stated in article 10 and article 11. Non-prescription medicines shall be excluded from the scope of the Code, as stated in Articles 10 (incentives) and 11 (hospitality and meetings), when established by a collaboration agreement between FARMAINDUSTRIA and ANEFP, regulating the promotion of these medicines and their control procedures, for the companies belonging to both Associations. information. This type of scientific information may be accompanied by publicity of the company, but regardless of the mass medium used (journals, bulletins, books or the like, or audiovisual materials stored on optical, magnetic, electronic or other supports), it shall have no connection with that scientific information, so that its handling, reading, display, listening or the like will be separate. VIII) Texts written or prepared by journalists as part of their professional work in regular editions, supplements, special issues or editions, etc. of newspapers, magazines, television or radio programs, etc., in which information about drug therapies, specific treatments or new medicines, scientific studies or papers or references to a specific medicine, lines of research or product launchings, press conferences, publications, etc. is presented as a news item, an interview, a debate, an editorial or in another similar format, are permissible, provided that a contractual relationship does not exist between the research laboratory or owner of the trade mark or medicinal products and the firm responsible for the edition or the author of the information. The companies adhered to the Code must comply with its spirit and letter, maintaining the same conduct standards in their relationship with all types of healthcare professionals. VII) Originals, reprints, literal translations of scientific articles and abstracts published in scientific sources of recognized prestige are acceptable, provided they do not contain printed, stamped or electronically-linked trademarks or trade names of medicines, advertising slogans or other advertising material, related or not to this Provisions of the code 1. MARKETING AUTHORIZATION 1.1. A medicinal product cannot be promoted prior to the grant of the marketing authorization allowing 5

7 6 its commercialization. This prohibition also covers medicines authorized in another country, which have not obtained marketing authorization in Spain. This regulation, however, does not imply a limitation to the right of the scientific community to be fully informed about medical and scientific progress, nor it intended to restrict complete and adequate exchange of scientific information related to medicines or medicinal substances, including appropriate and objective dissemination of research findings in the scientific communication media and scientific congresses All parts of the advertising of a medicinal product must be consistent with the information contained in the applicable summary of product characteristics and with the approved indications. 2. INFORMATION TO BE MADE AVAILABLE 2.1. All printed promotional material should include the following information in a clear and legible form: a) Essential information consistent with the data in the summary of product characteristics, specifying the date on which it was prepared or last revised. b) The prescription and dispensing conditions of the medicinal product. c) The different presentations of the medicinal product and, when appropriate, the dosage and/ or pharmaceutical form. d) The selling price, the conditions for reimbursement by the National Health System and, when appropriate and feasible, the estimated cost of the treatment For audiovisual material such as films, video recordings and the like, and for interactive data systems, the information may be provided: a) In a document which is made available to all persons to whom the material is shown or sent. b) By inclusion on the audio-visual recording or in the interactive data system itself. In this case, the information shall be included in the manner technically feasible and adapted to the chosen medium, but guaranteeing rapid and comprehensible access to information in the applicable summary of product characteristics. When the information is included in an interactive data system, instructions for accessing it must be clearly stated In accordance with national law, where the advertising is intended only as a reminder and the medicinal product has been authorized for at least two years, the requirements of paragraph 2.1. above need not be complied with, provided the advertising includes no more than the name of the product. In this case, the name of the medicinal product must be included and, if this is a brand name or an invented name and the product contains a single drug substance, it must be accompanied by the Spanish Official Name or, if unavailable, the International Nonproprietary Name. The product logo and the name and logo of the pharmaceutical company may also be included, but no other information Printed information or documentation supplied by pharmaceutical companies to doctors to be given to patients regarding certain medicines which, due to the complexity of their dosage, route of administration, etc. require the provision of additional information, will not be considered promotional material, provided that this information is intended to improve treatment compliance. 3. INFORMATION AND ITS RATIONALE 3.1. Information about medicinal products should be accurate, balanced, fair, objective and sufficiently complete to enable the recipient to form his or her own opinion of the therapeutic value of the concerned medicine. It should be based on an up-to-date evaluation of scientific evidence and clearly reflect that evidence; it should not mislead by distortion, undue emphasis, omission or in any other way.

8 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals 3.2. All artwork, including illustrations, graphs and tables, must conform to the letter and spirit of the Code. Graphs and tables should be presented in such a way as to give a clear, fair, balanced view of the topics covered, and should not be included unless they are relevant to the claims or comparisons being made. special merit, quality or property unless this can be substantiated The word new cannot be used to describe any medicine or presentation which has been generally available, or any indication which has been generally promoted, for more than two years in Spain. Special care should be taken to ensure that all graphic material included in the promotion is not misleading about the nature of the medicine (e.g. if the product is appropriate for use in children) or because of an argument or comparison (e.g. when incomplete or statistically non-relevant information, or unusual scales are used) Information and statements about untoward reactions should reflect the available evidence. It cannot be stated that a product has no adverse effects, or toxicity or addiction risks Trademarks or trade names of medicinal products from other companies may only be quoted if their ownership is clearly indicated Comparative advertising must always comply with the regulations on fair competition. It cannot be disparaging, and comparisons must be based on relevant and comparable aspects. At any rate, and particularly as regards comparative advertising, care must be taken to ensure that the sources on which statements are based are valid and immediately accessible to the competitor To avoid adaptations in presentations of data that may introduce biases or cause confusion, when promotional material refers to published studies, these should be quoted exactly. In the case of tables or figures, they should be reproduced literally. In accordance with the rules on data publication, the reference of the published work should be added. As an example of this, when the efficacy, safety or other properties of different drug substances are compared in promotional material, information such as the statistical significance of the results cannot be omitted, nor can the results of different clinical studies or trials be compared in the same table or graph, except when the source is a meta-analysis. Statistics, conclusions or any other data from different studies conducted using different methodologies cannot also be mixed or compared, unless they come from systematic reviews or meta-analyses in which homogeneity criteria are specified Exaggerated or all-embracing statements should not be made. Statements should not imply that a medicine or a drug substance has some 3.9. Any information, statement, or comparison included in promotional materials should be well founded. Such foundation (or rationale) should be provided to physicians and all other healthcare professionals on request. In particular, any comparison made between different medicines must be scientifically verified. Such rationale need not be provided, however, for statements related to the indications approved in the summary of product characteristics. 4. ACEPTABILITY OF MATERIAL 4.1. Any promotional activity or material should respect the special nature of the medicinal product and the professional standing of the target audience, and must not be likely to cause any offence or decrease the confidence in the pharmaceutical industry Promotional material should not imitate the products, slogans, presentation, or general layout adopted by other companies in a way that is likely to mislead or confuse Postcards, other exposed mailings, envelopes, or wrappers should not carry anything that 7

9 could be regarded as advertising to the general public All material relating to medicines and their uses that is sponsored by a pharmaceutical company must clearly state that it has been sponsored by that company. 5. TRANSPARENCY OF PROMOTION 5.1. Promotional material and activities should not be designed to disguise their actual purpose or nature Whenever a company finances, ensures, or directly or indirectly organizes publication of promotional material in newspapers or magazines, it should be expressly stated that such material is not included as an independent editorial topic, and the sponsoring company should be included in a visible place Any material related to medicines and their uses, whether promotional or not, that is sponsored by a company should clearly state that it has been sponsored by such company. 7. DISTRIBUTION OF PROMOTIONAL MATERIAL 7.1. Promotional material should be sent or distributed to those healthcare professionals for whom the particular information may be relevant. Except authorization from the competent Health Authority (e.g. vaccination campaigns), promotion directed to the public in general will not be allowed for medicines which can only be dispensed through facultative prescription Mailing lists for shipment of promotional material must be regularly updated. Requests by healthcare professionals to be removed from promotional mailing lists must be complied with All promotional activities will be conducted in accordance with applicable regulations concerning personal data protection In the international congresses and meetings organized by third parties where numerous healthcare professionals from other countries assist, those shall be informed regarding some medicines or indications without marketing authorization in Spain, only if: In consultations from the general public asking for advice on medical topics of a personal nature, a recommendation to consult a physician must be given. 6. USE OF REFERENCE QUOTATIONS 6.1. Quotations from medical and scientific literature or from personal communications should accurately reflect the opinion of the author Quotations relating to medicines taken from public broadcasts, for example on radio and television, and from private events, such as medical conferences or symposia, should not be used without the formal authorization of the speaker. (I) The information carried out or delivered is written in English or in any language pertaining to the countries where it is authorized, and (II) some text or warning such as this medicine is not commercialized in Spain or in the following countries or it is only authorized in or it is not authorized in Spain for the following indication should be indicated or signalled at least in Spanish with emphasized letters, clearly visible, in a continuous, lasting and readable way on the item or any commercial material. 8. PROMOTION VIA THE INTERNET 8.1. Promotional materials for medicines directed to healthcare professionals to be disseminated through the Internet must have a primarily technical-scientific or professional content.

10 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals 8.2. In addition, measures must be taken to ensure that this advertising is only accessible to these professional groups Promotional material must include a prominent and clearly legible warning indicating that the information contained on the web page is intended only for healthcare professionals qualified to prescribe or dispense medicines, and specialized training is therefore required for its adequate interpretation. 9. SCIENTIFIC SERVICE AND REVIEW OF PROMOTIONAL MATERIAL 9.1. Pharmaceutical companies must have a scientific service to compile and collect all information, whether received from medical representatives or from any other source, and to inform about the medicines which they market Promotional material should not be issued unless its final form, to which no subsequent amendments will be made, has been reviewed and checked by the scientific service of the company. practice of his/her professional activity, can carry out or determine the activities related to the medicine prescription, dispensation or administration cycle, including their relatives, with the exception of inexpensive gifts related to the practice of medicine or pharmacy. Therefore, the provision of gifts such as items for professional use in the practice of medicine or pharmacy or office items of insignificant value is permissible. Discounts for early payment or volume of purchase carried out by distributors (wholesaler or pharmaceutical company if it directly carries out the distribution) to pharmacies are considered an exception from the previously stated prohibition. These may make up to a maximum of 5% for the medicines reimbursed by the National Health System, which may be extended up to 10% in the case of generic drugs, provided that: a) They do not induce the purchase of a product against those of its competitors. b) Such practices remain recorded in the pertaining invoice. The scientific service should guarantee that it has examined the final version of the material and that in their opinion it is in accordance with the applicable rules regulating advertising and with this Code, is consistent with the marketing authorization, and particularly with the information included in the approved summary of product characteristics and patient leaflet, and is a fair and faithful presentation of the data about the medicine. 10. INCENTIVES Gifts will be considered to be inexpensive when their market price does not exceed 10 Euros. Market price refers to the amount that a recipient would normally pay for the purchase of one unit of said product in Spain The provision of objects such as books or other materials on optical, magnetic, electronic or similar supports on medicine or pharmacy topics sponsored by the company is excepted, provided that they comply with applicable legal requirements To ensure the independence of the decisions related to the prescribing, dispensing, or administering of medicines with regard to business interests, no gifts, bonuses, pecuniary advantages or benefits in kind may be granted, offered, or promised by those who have direct or indirect interests in the manufacture, production or commercialization of medicines to healthcare professionals or to any person who, in the The provision of gifts of higher value or which are not of a scientific or technical nature is not permissible. It is also not permitted to provide directly or indirectly portable electronic devices susceptible to personal use, even if they may have a professional use These gifts must include all the information specified in article 2.1. However, when the 9

11 10 medicinal product has been authorized for at least two years and reminder advertising is thus allowed, only the information specified in article 2.3 can be included. 11. HOSPITALITY AND MEETINGS The following standards shall apply to every type of event (congresses, conferences, symposia, meetings or any type of similar activity, including but not limited to expert meetings, investigator meeting, training meetings, etc.) organized or sponsored by a pharmaceutical company or under its control, and to all the participants therein, whether they might be healthcare professionals, or any other person who, in the practice of his/her professional activity, can carry out or determine the activities of prescribing, buying, distributing, dispensing or administrating a medicine Pharmaceutical companies may organize or collaborate in events of a purely scientific-professional nature. It is not permitted to organize or collaborate in events containing elements or activities of an entertainment or recreational nature. This prohibition does not include welcome cocktails, work lunches and dress dinners that are usually included in the official programs of congresses and scientific meetings, provided they are reasonable and moderate and do not include additional elements (cultural, leisure or entertainment, etc.) Hospitality at professional and scientific events should be reasonable at all times, and its cost cannot exceed what recipients would normally be prepared to pay for themselves in the same circumstances. The concept of hospitality includes the payment of actual travel, inscription and subsistence expenses by the company, which must be reasonable and not out of proportion, and be limited to the days on which the scientific meeting is planned to be held. Hospitality cannot be extended beyond a reasonable period after the event, nor will it include the sponsorship or organization of recreational events (sports, leisure activities, etc.). Hospitality must always be secondary to the main purpose of the meeting. The scientific goals must represent the main focus in the organization of such meetings. Hospitality provided by a pharmaceutical company should be limited to include the strictly necessary logistic means in all cases reasonable and moderate that allows the healthcare professional to attend the event, and no other expense Hospitality should not be extended to persons other than healthcare professionals Payments may not be made to physicians or groups of physicians, either directly or indirectly, for rental for rooms to be used for meetings, unless it is duly accredited that such rooms are intended for scientific or professional meetings When meetings, congresses, symposia and similar events are sponsored by pharmaceutical companies, that fact must be disclosed in all of the papers relating to the meetings and in any published paper, speech, or document related to such meetings The payment of reasonable fees and reimbursement of out of pocket expenses, including travel, for speakers and moderators at meetings, congresses, symposia, and similar scientific or professional events, is permissible Pharmaceutical companies established in Spain which belong to international corporations with headquarters or subsidiaries or other associated companies located in foreign countries shall be responsible for compliance with this Code by these associated companies with regard to promotional activities directed to healthcare professionals practicing in Spain, when they are invited to events held in foreign countries or in the Spanish territory Scientific and promotional meetings and events organized or sponsored by pharmaceutical companies must be notified previously in accordance with the provisions in the Rules of Procedure of the Control Bodies of the Code.

12 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals Failure to notify a scientific and promotional meeting or event, when such notification is obligatory, shall constitute an infringement of this Code Companies cannot organize or promote events held outside Spain (international events) unless this makes more sense from a logistic viewpoint because: a) the majority of participants invited are foreigners; or Medical representatives should not use any incentive or subterfuge to gain an interview. No fee shall be paid or offered for the grant of an interview Medical representatives should ensure that the frequency, timing and duration of visits to healthcare professionals, administrative staff in hospitals, and health authorities and the like, together with the manner in which they are made, do not cause inconvenience. b) a resource or expertise that is relevant and the main object of the event is located outside Spain. This case (b) shall have the previous authorization of the Code of Practice Surveillance Unit Both when interviews are agreed and conducted, medical representatives should from the very outset take any reasonable steps to ensure that they do not mislead as to their identity or that of the company they represent. If international events are organized or sponsored, in addition to the Spanish Code, companies must also respect the specific provisions of the Code of Practice for the Promotion of Medicines of the country where the event is held, as set forth at article Medical representatives must notify to the scientific service of the pharmaceutical company any information they receive from the professionals about the use of the medicines they promote, with particular reference to any untoward reactions reported to them by the persons they visit Companies should meet the criteria stated in the applicable codes as regards selection and sponsorship of healthcare professionals for their attendance to events In no case can money be offered to merely compensate the time used by healthcare professionals to attend the event. 12. PHARMACEUTICAL COMPANY STAFF Medical representatives should be adequately trained by or on behalf of the company which employs them, and shall have an adequate scientific knowledge to present information on their company s products in an accurate and responsible manner Medical representatives should approach their duties responsibly, complying with the applicable law and ethical rules, as well as the provisions in this Code At each visit, medical representatives will provide to the person visited, or have available for him/her if requested, the current summary of product characteristics for each medicinal product they promote, accompanied by information on the different pharmaceutical forms and dosages, the prescription and dispensing conditions of the medicinal product, price information, the conditions of reimbursement by the National Health System, if applicable, and when feasible, the estimated cost of the treatment Companies shall take effective measures to ensure that their medical representatives and all company personnel related in any way with the preparation or approval of promotional material or of information intended for healthcare professionals are fully conversant and comply at all times with the provisions in this Code and the relevant regulations on the advertising and promotion of medicines. 11

13 Likewise, they shall adopt efficient measures and watch so the interactions between the medical representatives and other pharmaceutical company staff with the healthcare professionals (including any other person who, in the practice of his/her professional activity, can carry out or determine the activities of prescribing, buying, distributing, dispensing or administering a medicine), complies with this Code and the applicable regulation provisions at any given time Medical representatives must have adequate training to disseminate the characteristics of the medicinal products. It is the responsibility of each company to ensure (through tests, additional training, joint work, etc.) on a regular basis that the training of their representatives is adequate The same rules as for medical representatives will be applicable for representatives who call on retail pharmacies, who should comply with the applicable law on the promotion of medicines and with ethical principles and provisions of this Code Each company should appoint at least one adequately qualified employee or manager, who will be responsible for internal supervision of Code compliance. An implementation guide shall explain the basic principles and mechanisms for internal control to be respected by all pharmaceutical companies. In any case, the existence of persons responsible for internal supervision does not exempt the maximum representatives of the companies from their responsibilities A sample of a medicine should be no larger than the smallest presentation of the medicine available on the national market Each sample must bear the statement free sample-sale forbidden, and the coupon of the medicinal product must be suppressed or cancelled. Whenever samples are provided, a copy of the current summary of product characteristics must always be given, together with updated price information, conditions of reimbursement in the National Health System, if applicable, and when feasible, an estimate of the cost of treatment No samples of medicinal products containing psychotropic or narcotic substances, as defined in international agreements, medicines that may cause dependency or give rise to public health problems from improper use, and any other medicinal products as determined by the relevant authorities may be given Samples distributed through medical representatives will be directly provided to healthcare professionals qualified to prescribe medicinal products who have requested them or persons authorized to receive them on their behalf Sample distribution in hospitals must comply with individual hospital requirements and procedures Companies must have adequate systems for control and accountability of samples they distribute. 13. SAMPLES 14. STUDIES In accordance with national law, a limited number of free samples may be supplied to healthcare professionals qualified to prescribe medicinal products, to familiarize themselves with new medicines, provided they are requested by the professionals Samples can be provided for a maximum of two years from the date of marketing authorization of the medicinal product Clinical trials. The term clinical trial comprises all the research carried out on human beings in order to determine or confirm the clinical, pharmacological and/or other pharmacodynamic effects, and/or to detect the adverse reactions, and/or to study the absorption, distribution, metabolism and excretion of one or various medicines under investigation, with a view to determining their safety and/or their efficacy.

14 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals Pharmaceutical companies shall carry out this kind of trials in accordance with applicable regulation, thus obtaining prior agreement of the Clinical Research Ethics Committee, the approval of each one of the Centers where it will take place and the authorization from the Spanish Agency for Medicinal Products and Medical Devices (AEMPS) Post-authorization studies. A post-authorization study is any epidemiological or clinical study carried out during the marketing of a medicinal product in accordance with the conditions authorized in the summary of product characteristics or under normal conditions of use, in which the medicinal product(s) of interest are the main factor of exposure investigated. This type of study may take the form of a clinical trial (art 14.1) or an observational study. An observational study is a study in which the medicinal products are prescribed in the usual manner in accordance with the conditions established in the marketing authorization. The assignment of a patient to a given therapeutic strategy shall not be decided beforehand by a trial protocol, but by the standard practice of medicine, and the decision to prescribe a given medicinal product shall be clearly dissociated from the decision to include the patient in the study. No diagnostic or follow-up intervention shall be applied to patients other than such as are standard in clinical practice, and epidemiological methods shall be used to analyze the data collected. PAS). These are observational studies in which the main factor of exposure investigated are not medicines, as is the case, for instance, of studies on incidence or prevalence of diseases. These observational studies should also be conducted in compliance with the requirements of applicable legislation Market research studies. Market research (including social and opinion research) consists of the systematic collection and interpretation of information on individuals or organizations, using statistical and analytical methods and techniques of the social sciences, applied to obtain new perceptions or provide elements of support for decision-making. In these studies, the identity of respondents is not revealed to the user of the information without their specific consent, nor are respondents contacted for sales actions as a direct result of having provided the information. Without prejudice to the applicable regulation, there is a general framework for ethical action in which market research should be conducted, embodied in the ICC/ ESOMAR International Code of Marketing and Social Research Practice of the European Society of Marketing and Opinion Research (ESOMAR). In the specific case of the pharmaceutical industry, the framework of selfregulation in this area comprises the Code of Conduct of the European Pharmaceutical Marketing Research Association (EphMRA). Post-authorization observation studies shall be those epidemiological studies that meet the conditions of being post-authorization and observational. These must be conducted in accordance with the requirements of applicable legislation, among others, submission of the documentation to the AEMPS for registration and classification, submission to a Clinical Research Ethics Committee for evaluation, etc. These studies should in no case be undertaken as a procedure to promote a product or to induce prescription by healthcare professionals. Legislation also covers conducting observational studies that are not post-authorization studies (non- The present regulation does not seek to replace the EphMRA Code, but only for arranging certain mechanisms guaranteeing adequate conduct of these studies within the scope of this Code. The EphMRA Code shall be of subsidiary application for correct interpretation of this Code. All market research studies that are carried out at the initiative of a pharmaceutical company, at the initiative of several pharmaceutical companies that share marketing strategies of a product or when a pharmaceutical company acquires the study from a third party (research institute, scientific society, etc.) that has undertaken the work on its own 13

15 initiative shall be subject to the provisions of this article. Market research studies must meet the following requirements: I) Ignorance of the identity of the individuals participating in the study. Pharmaceutical companies shall not be able to know before, during or after its conduct, the identity of the individuals who took part in the study. II) Anonymous nature of the information collected. Pharmaceutical companies shall not have the possibility of linking by name each of the study participants with the data or opinions obtained. In addition, to ensure that market research studies do not represent an inducement to prescription or contain an incentive prohibited by the Code, pharmaceutical companies undertake to: I) Communicate them prior to their start, in accordance with the Rules of Procedure of the Control Bodies of the Code. II) Ensure the study does not modify the physicians prescriptions habits or the pharmacists dispensing habits. III) Have a written protocol in which its objectives, methodology, expected results and its use are clearly established. III) Pooled processing of the responses or data obtained. IV) Proportionality between the universe and the sample. Quantitative market research studies pursue a level of representativeness of the universe. When to calculate sample size, parameters are used other than those generally accepted in market research (simple random sample, a margin of error of 5%, 95% confidence and 50% heterogeneity level), prior authorization by the Code of Practice Surveillance Unit shall be required. V) The individual who participates in the study does not know and has no opportunity to link its conduct with a pharmaceutical company or a specific product. Therefore, the sales network of the pharmaceutical company cannot play any role in the conduct and implementation of study. VI) The study results and the data obtained will not be advertised or used in promotional material. In this respect, written agreements shall be signed with the professionals and/or the entities with which the studies will be carried out on one hand, and the company sponsoring the study on the other hand, specifying the nature of the services to be provided, the professionals participation and payment conditions, etc. IV) Payment to participating professionals must be based on market criteria and be proportionate to the time devoted, the work done, and the responsibilities assumed, and must be adequately documented. Payment shall be monetary. Exceptionally, and with prior authorization of the Unit, some payments may be made in kind. V) Guarantee that conduct of the study does not constitute an inducement to recommend, prescribe, purchase, supply, sell or administer specific medicinal products. 14 Any exception to these requirements should have prior approval of the Code of Practice Surveillance Unit. In particular, requirements i, ii and v will be developed in the guide for market research studies linked to a product. VI) Be approved prior to their conduct by the pharmaceutical company scientific service or by the compliance officer foreseen in Article of the Code.

16 Spanish Code of Good Practices for the Promotion of Medicines and Interaction with Healthcare Professionals These requirements shall be applicable irrespective of the methodologies, sources, or techniques applied for its conduct, for example: survey method, observation, experimental designs, ethnographic techniques, expert groups, qualitative techniques, etc. Failure to communicate the studies referred to in article 14.3, when such communication is compulsory, shall constitute an infringement to this Code Any other type of activity, practice, or initiative for information collection not foreseen in the foregoing paragraphs or in articles 16 and 17 of the Code and intended to involve directly or indirectly payment to healthcare professionals, will be considered a promotional action and, as such, shall be subject to the provisions in this Code, particularly in Article 10 (Incentives). 15. DONATIONS AND GRANTS Donations, grants and benefits in kind to institutions, organizations or associations that are composed of healthcare professionals and/or that provide social or humanitarian assistance services or conduct research education or training (that are not otherwise covered by this Code or the Spanish Code of Practice on Interactions between the Pharmaceutical Industry and Patient Organizations) are only allowed if: (I) they are made for the purpose of supporting healthcare, research, education/training or social or humanitarian assistance; (II) they are documented and kept on record by the donor/grantor; and 10.4, direct or indirect donation of portable electronic devices susceptible to personal use, even if they may have professional use, is not permitted. To encourage transparency, companies are encouraged to make publicly available information about donations, grants or benefits in kind made by them, covered in this Section. 16. SERVICES RENDERED BY ENTITIES INTEGRATED BY HEALTHCARE PROFESSIONALS Contracts between companies and institutions, organizations or associations of healthcare professionals under which such institutions, organizations or associations provide any type of services to companies (or any other type of agreement from which funding not covered by this Code arises) are only allowed if such services: I) are provided for the purpose of supporting health assistance, research, teaching and training, or the organization of professional or scientific events; II) are gathered on a document of which the contracting pharmaceutical company keeps a record; III) do not constitute an inducement to recommend, prescribe, purchase, supply, sell or administer specific medicinal products; and IV) are approved, prior to the contract, by the pharmaceutical company scientific service or by the compliance officer foreseen in article of the Code. III) they do not constitute an inducement to recommend, prescribe, purchase, supply, sell or administer specific medicinal products. Donations and grants to individual healthcare professionals are not permitted under this section, except companies sponsorship of healthcare professionals to attend international events which is covered in Article 11. Hence, in accordance with article Agreements with these entities involving paid participation of at least 20 healthcare professionals must be notified by pharmaceutical companies which organize or sponsor them in their majority, prior to their start, in accordance with the Rules of Procedure of the Control Bodies of the Code. Failure to notify these agreements will constitute an infringement of this Code. 15

17 17. SERVICES PROVIDED BY HEALTHCARE PROFESSIONALS It is permitted to use healthcare professionals as consultants and advisors, whether in groups or individually, for services such as speaking at and chairing meetings, involvement in medical/scientific studies, clinical trials or training services, participation at advisory board meetings, and participation in market research where such participation involves remuneration and/or travel and boarding expenses. The arrangements covering legitimate provision of such services must meet the following conditions: a) a written contract or agreement is agreed in advance of the commencement of the services which specifies the nature of the services to be provided and, subject to clause (g) below, the basis for payment of those services; b) a legitimate need for the services has been clearly identified in advance of requesting the services and entering into arrangements with the prospective consultants; g) Payment to participating professionals must be based on market criteria and be proportionate to the time devoted, the work done, and the responsibilities assumed, and must be adequately documented. Payment shall be monetary. Exceptionally, and with prior authorization of the Unit, some payments may be made in kind. h) are approved, prior to the contract, by the pharmaceutical company scientific service or by the compliance officer foreseen in article of the Code When the contracting of this kind of service for a single project or activity involves paid participation of at least 20 healthcare professionals, the pharmaceutical company must notify it before it begins, in accordance with the Rules of Procedure of the Control Bodies of the Code. Failure to notify these services shall constitute an infringement of this Code. 16 c) the criteria for selecting consultants are directly related to the identified need and the persons responsible for selecting the consultants have the expertise necessary to evaluate whether the particular healthcare professionals meet those criteria; d) the number of healthcare professionals retained is not greater than the number reasonably necessary to achieve the identified need; e) the contracting company maintains records concerning, and makes appropriate use of, the services provided by consultants; f) the hiring of the healthcare professional to provide the relevant service is not an inducement to recommend, prescribe, purchase, supply, sell or administer a particular medicinal product; and In their written contracts with consultants, companies are strongly encouraged to include provisions regarding the obligation of the consultant to declare that he/she is a consultant to the company whenever he/she writes or speaks in public about a matter that is the subject of the agreement or any other issue relating to that company. Similarly, companies that employ, on a part-time basis, healthcare professionals that are still practicing their profession are strongly encouraged to ensure that such persons have an obligation to declare his/ her employment arrangement with the company whenever he/she writes or speaks in public about a matter that is the subject of the employment or any other issue relating to that company. This section applies in all cases, even though the Code does not cover corporate advertising of pharmaceutical companies.