OVERVIEW OF GUIDELINES ON SALES INFORMATION PROVISION ACTIVITIES
OVERVIEW OF GUIDELINES ON SALES INFORMATION PROVISION ACTIVITIES
The activities of pharmaceutical companies in modern era has become increasingly complex and diverse, and there are increasing numbers of cases where it is difficult to determine whether they meet the above three requirements of advertisement, such as medical information provided by the so-called Medical Science Liaison (MSL), media seminars held as a function of corporate public relations, press releases for investors, and disease awareness raising for patients. Considering these changes, the Sales Information Provision Activities Guidelines (the “Guidelines”) covering sales information provision activities, which are broader than advertisement, has become effective since April 1, 2019.
1. Applicable body
The Guidelines apply to marketing authorization holder of pharmaceuticals and their entrustees
and partners (including so-called co-promotion partners) and pharmaceutical wholesalers (collectively referred to as the "marketing authorization holder of pharmaceuticals").All employees of the marketing authorization holder of pharmaceuticals shall be subject to the
Guidelines irrespective of the names or departments such as Medical Representative (MRs, as stipulated in Article 2, Paragraph 5, of the GVP Ministerial Ordinance), Medical Science Liaison (MSL).
Even if the company's internal rules stipulate that the activities of the Medical Affairs Department and MSL be clearly separated from sales information provision activities, the applicability of
the Guidelines is assessed and judged on a case-by-case basis according to the actual activities conducted, and such internal rules do not automatically exclude the applicacbility of the
Guidelines.Also, if a lecture by an external expert (healthcare professional, etc.) at an event sponsored
by the marketing authorization holder of pharmaceuticals meets the requirements of "sales information provision activities" considering the objective and purpose of the event, such lecture will
be subject to the Guidelines.
2. Applicable Conducts
Guidelines define sales information provision activities as "provision or conveyance of
information by the pharmaceuticals marketing authorization holder, etc. of information relevant to a particular ethical pharmaceuticals in anticipation of sales promotion thereof through
improvement of recognition of the name or effectiveness or safety of the relevant ethical pharmaceuticals, irrespective of whether such activities are active or passive, and includes raising
awareness of diseases relating to efficacy or the effects of the ethical pharmaceuticals (including that which targets the general public)." The Guidelines are designed to improve the current
status of advertisement or advertisement-similar activities that are difficult to determine applicability of advertisement-related regulations, such as conducts that are not clearly false or
exaggerated but are considered to encourage inappropriate use or misuse. Therefore, it should be noted that "in anticipation of sales promotion" has wider meaning than the “induction” in the
three requirements of advertisement ("clearly intended to induce consumers to purchase products"). Even disease awareness-raising activities conducted can be within the scope of the
3. Principles and Prohibitions of Information Provision
The Guidelines include the following four principles of sales information provision activities:
Efficacy, effect, dosage or administration, etc., of the ethical pharmaceuticals to be provided is within the approved scope.
Necessary information shall be provided and information to be provided shall not be selected arbitrarily, such as provision of information on safety that includes side effect, not just the effectiveness of the ethical pharmaceuticals.
Information provided must be accurate and based on scientific and objective grounds, and the grounds can be presented. Scientific grounds must be grounds for which objective evaluation and verification by a third party is possible, including the original data thereof, or which have undergone assessment of appropriateness (referee reading of paper, etc.) by a third party (including evaluation materials or assessment reports used for assessment for approval).
Information cited in sales information provision activities materials must have the original citation source clearly stated. In addition, for external research and studies, if there has been any provision of items, moneys or labor, etc. by the pharmaceuticals marketing authorization holder in relation to implementation of examination on sources of citations, studies or preparation of papers, etc., the specific details thereof must be clearly stated. In addition, for external research and studies, only those that observe the “Clinical Research Act” (Act No. 16 of 2017), “Ethical Guidelines for Medical and Health Research Involving Human Subjects” (Announcement No. 3 of MEXT and MHLW of 2014), and other similar guidelines may be used.
In addition, the following seven terms are referred to as "prohibited activities."
Use of false or extravagant wording or language that induces misperceptions, or conduct of other acts prohibited in advertising regulations
Recommendation of methods of use other than the approved efficacy, effect, dosage or administration, etc. This shall be the same even in the case where approval, etc. is obtained in foreign countries.
Inducement to prescription or use, etc. specific ethical pharmaceuticals arbitrarily, without scientific or objective grounds
Promotion of own products by slandering or defaming products of other companies
Excessive emphasis on morbidity or symptoms of disease, and inspiration of worry
Recommendation of treatment alone (including diagnosis and prevention; the same shall apply hereinafter) with ethical pharmaceuticals in awareness raising of disease in the general public, or creating the misperception that there is no method of treatment other than treatment with ethical pharmaceuticals
Use of other language that may induce improper use or misuse of ethical pharmaceuticals
RESPONSIBILITIES OF MANAGEMENT
4. RESPONSIBILITIES OF MANAGEMENT
The Guidelines clearly states that the management of the marketing authorization holder of pharmaceuticals is responsible for its employees’ every operation-related conduct associated with sales information provision activities. The Guidelines also require the management to take leadership in the establishment of the necessary internal systems for implementing appropriate sales information provision activities. The primary contents of the responsibility of the management are as follows.
Management shall establish a division to perform monitoring of appropriateness, etc. of sales information provision activities materials and sales information provision activities themselves (Sales Information Provision Activities Supervisory Division (“Supervisory Division”)) to confirm that the company is conducting sales information provision activities appropriately, clarify the person responsible, and grant authorities to enable supervision and instruction such as necessary monitoring, etc. to Supervisory Division or person in charge of sales information provision activities.
Management shall establish an Assessment and Supervisory Committee that includes persons who are independent from the company, and have the Committee give necessary advice to the persons responsible for activities in Supervisory Division.
Supervisory Division shall report on the status of implementation of sales information provision activities to management, and if necessary for proper sales information provision activities, and submit opinions to management based on advice from the Assessment and Supervisory Committee, and management shall take proper measures based on the relevant opinions.
Management shall properly reflect in evaluations and remunerations for officers and employees, regardless of whether or not the person engaged in or had others engage in proper sales information provision activities.
In addition, management shall regularly carry out education for officers and employees so that proper sales information provision activities may be conducted.
Management shall have Supervisory Division or person in charge of sales information provision activities prepare necessary manuals so that operations relating to sales information provision activities will be performed properly, and also prepare operation records (including records of contents of oral explanations, etc. in sales information provision activities), and have the relevant operation records stored properly. In addition, when MHLW, related local government or PMDA requests submission of related materials, management shall have the activity status reported promptly together with sales information provision activities materials.
When management becomes aware of the fact that improper sales information provision activities are being conducted at the company, management shall promptly conduct an investigation of the complete facts and take the required measures such as correction or recurrence prevention. In addition, management itself must confirm the status of progress and instruct on taking additional measures if necessary, and for violators, strictly conduct proper evaluation and disposition.
Management shall establish a contact window that can be recognized by external parties that accept complaints about sales information provision activities, and if there is a complaint, Supervisory Division shall swiftly investigate the complete facts, and have the necessary measures taken.
Management shall work on companies to whom sales information provision activities are commissioned or affiliated, and pharmaceuticals wholesalers to conduct proper sales information provision activities.
ROLES OF SUPERVISORY DIVISION
Supervisory Division shall periodically conduct supervision and instruction such as monitoring for sales information provision activities by MRs, MSLs, etc. In principle, the Medical Affairs Department may not be the body of Supervisory Division since it may become the supervised department for sales information provision activities of MSLs, etc. It is possible to appoint a responsible person within Supervisory Division for reviews and monitoring respectively, provided, however, since it is necessary to implement consistent measures under clear responsibility, the responsible person of Supervisory Division who oversees both functions must be clarified.
It is also preferred that the person in charge of monitoring belongs to a department independent of sales information provision activities. However, when Supervisory Division considers that persons in charge of sales information provision activities (this could include personnel in medical department) are necessary for implementing more effective monitoring, utilizing the experiences of such persons will not be denied. Even in this case, however, when a person in charge of sales information provision activities carries out monitoring-related activities, it is necessary to establish a system for conducting appropriate monitoring by objectively defining monitoring procedures and evaluation items, and clarifying the status of such persons in Supervisory Division.
(2) Review of Materials
Materials for sales information provision activities must be reviewed by Supervisory Division prior to use. In doing so, Supervisory Division shall approve the materials based on advice of Assessment and Supervisory Committee.
(3) Handling of Complaints
When there are complaints regarding the implementation of sales information provision activities, Supervisory Division shall promptly investigate the facts and take necessary measures.
(4) Report and Provision of Opinions
Supervisory Division shall regularly report to Assessment and Supervisory Committee on the status of sales information provision activities, and the Assessment and Supervisory Committee shall provide necessary advice to Supervisory Division. Supervisory Division shall report the status of sales information provision activities to management and, when necessary, provide opinions to management based on advice of Assessment and Supervisory Committee.
ASSESSMENT AND SUPERVISORY COMMITTEE
Assessment and Supervisory Committee is required to take the role of, independent from the interests of the marketing authorization holder of pharmaceuticals, by providing advice to Supervisory Division, ensuring proper implementation of reviews of materials for sales information provision activities and supervision and instruction such as necessary monitoring. “Persons who are independent from the company” must be carefully selected in view of capability to provide resolute advice from the standpoint of outside parties irrespective of the interests of the marketing authorization holder of pharmaceuticals. In addition, from the viewpoint of ensuring proper advice by Assessment and Supervisory Committee given to Supervisory Division, the person who reviews of materials for Supervisory Division shall not be a member of Assessment and Supervisory Committee. Therefore, when the company positions outside lawyers or other experts who are currently reviewing materials for Supervisory Division as “persons who are independent from the company”, they shall be positioned as a member of Assessment and Supervisory Committee, not a member of Supervisory Division.
Assessment and Supervisory Committee may be established either inside or outside Supervision Division. In either case, it is important to fully utilize advice of Assessment and Supervisory Committee and to establish a system that appropriately reflects the viewpoint of third parties in the monitoring and review of materials.
In addition, Assessment and Supervisory Committee may be entrusted to an appropriate external organization capable of providing necessary advice to the person in charge of Supervisory Division; provided, however, even in this case, Supervisory Division shall assume responsibility for supervision and guidance such as monitoring and reviews.
Evaluation and Education
Management shall confirm whether or not officers and employees have implemented appropriate sales information provision activities and shall appropriately reflect the result of such confirmation in their evaluations. For example, evaluation and remuneration system which is detathed from “sales supremacism” model should be considered, such as setting conducting or having subordinates conduct appropriate sales information provision activities as an evaluation item for persons belonging to departments in charge of sales information provision activities.
Preparation of Manuals
Management shall make the department or persons in charge of the sales information provision activities prepare the manuals necessary for the proper implementation of operations associated with sales information provision activities. Also, when MHLW, relevant municipalities, or PMDA requests the submission of data related to sales information provision activities, the status of the activities shall be promptly reported by submitting manuals in addition to materials for sales information provision activities.
To ensure appropriate sales information provision activities in compliance with the Guidelines, it is necessary to establish manuals based on the operations of each company, including items such as methods of sales information activities, preparation of operation records, handling of materials, and to make necessary revisions on the manuals in accordance with the operations.
Record Preparation and Retention
Management shall prepare operation records (including a record of the contents of oral explanation, etc. in the sales information provision activities) and have the relevant operation records appropriately retained. In addition, when MHLW, relevant municipalities, or PMDA requests the submission of data related to sales information provision activities, the status of the activities shall be promptly reported by submitting operation records in addition to the materials and other information provided by sales information provision activities.
In the operation records, information such as the date and time, the name of the medical institution to be visited, the name of the physician/pharmacist, and the materials to be used may be entered when activities are based on the materials that have been reviewed by Supervisory Division. However, when an explanation is made on the matters not included in the materials, a record of the specific details, including a summary of communication with the physician and pharmacist, is required.
Handling of Complaint
Management shall establish a contact window that can be recognized by external parties that accept complaints about sales information provision activities, and in the event of a complaint, Supervisory Department shall promptly investigate the facts and take necessary measures.
Companies may inform the outside of the contact window in a manner deemed appropriate depending on the situations of each company.
PROVISION OF UNAPPROVED OR OFF-LABEL INFORMATION
When there is a request from healthcare professionals, a patient or organization thereof for provision of information related to unapproved pharmaceuticals or off-label pharmaceuticals, the relevant information can be provided by satisfying all of the following conditions:
Provision shall be separated from ordinary sales information provision activities.
Contents provided as information shall be limited to the required details, and recipients of the information shall be limited to the requestors.
Requests must not be falsified to create the appearance that medical personnel or patients requested provision of information.
Information to be provided shall not have false or extravagant contents, and must be scientific, objective and accurate. In addition, in provision of information, summarization, omission or emphasis, etc. shall not be performed.
When providing a paper, etc. based on testing and research involving pharmaceuticals marketing authorization holders, the relevant testing and research must be properly managed in accordance with the Ministry Order on Standards for Implementation of Clinical Testing of Pharmaceuticals (MHLW Order No. 28 of 1991) or “Clinical Research Act” (Act No. 16 of 2017) or similar laws and regulations.
Disadvantageous information such as increasing risks of side effects or inability to certify significant differences in clinical testing, etc. shall also be provided properly.
Clearly convey the fact that the efficacy and effect, dosage and administration, etc. are not approved for the ethical pharmaceutical for which the information is being provided.
Records must be prepared and stored relevant to information provision such as on the background, recipient of information, or details of provision.
In providing unapproved pharmaceuticals or off-label pharmaceuticals, the information provided must be accurate based on scientific and objective evidence. However, the review reports and adverse reaction information published by overseas administrative bodies such as treatment guidelines, peer-reviewed original articles, FDA and EMA, and foreign package inserts can be used as a basis for judging whether they are accurate based on scientific and objective evidence, since they have been assessed by academic societies, overseas administrative organizations, etc. In addition, when information is requested on cases for which the number of patients is limited, the information may be provided without arbitrary selection of case reports, clearly stating that there is insufficient evidence. Negative information, including case reports, should be provided.
When information on the status of development of unapproved pharmaceuticals or additional indications (clinical trial information) is requested by patient organizations, information on the following sites can be provided in accordance with the Guidelines; University Hospital Medical Information Network (UMIN), Japan Pharmaceutical Information Center (JAPIC), Japan Medical Information Center (JMACCT), clinical studies conducted at medical institutions based on the Clinical Research Act (Clinical Research Plan/Summary Publication System: JRCT), main clinical studies and clinical studies conducted from a humanitarian perspective (expanded clinical trials) published at the PMDA website, information on ClinicalTrials.gov.