Medical Science Liaison Before Approval: Where Law and Codes Draw the Line to Promotion

Before approval, a medicinal product may not be promoted. Information may be given when somebody asks. Between those two sentences lies the work of the Medical Science Liaison in the months before launch, and the line between them is set in texts that are shorter than most of the SOPs implementing them.

This article lays the texts side by side: Articles 86 and 87 of Directive 2001/83/EC, Sections 1, 3a and 7 of the German Heilmittelwerbegesetz (HWG), Sections 75 and 76 of the German Arzneimittelgesetz (AMG), the FSA Code for healthcare professionals in the version of March 20, 2024, the EFPIA Code of Practice in its 2026 consolidated version, and the sponsor rules of Regulation (EU) No 536/2014 for investigator-initiated trials.

What advertising is: Article 86 and Section 1(5) HWG

Article 86(1) of Directive 2001/83/EC defines advertising of medicinal products as any form of door-to-door information, canvassing activity or inducement designed to promote the prescription, supply, sale or consumption of medicinal products. The list of examples expressly includes visits by medical sales representatives to persons qualified to prescribe medicinal products.

The definition hangs on the purpose of the activity. A piece of information is advertising if it is designed to promote prescription or consumption; it is not if that purpose is absent. The department the information comes from is not in the text. A medical affairs function can therefore advertise, and a sales force can answer a question.

Article 86(2) takes four things out of the advertising title, among them "correspondence, possibly accompanied by material of a non-promotional nature, needed to answer a specific question about a particular medicinal product". Next to it stand factual announcements on pack changes and adverse reaction warnings, trade catalogs and price lists without product claims, and health information without any reference to a medicinal product.

German law adopts the exemption almost word for word. Section 1(5) HWG: the Act does not apply to correspondence and documents that do not serve advertising purposes and that are needed to answer a specific question about a particular medicinal product. Section 1(8) exempts the summary of product characteristics, approved educational material and the public assessment report when transmitted on request.

The exemption has three elements, and each is a documentation question. The request has to be specific, that is, a particular question about a particular medicinal product. The answer may not serve an advertising purpose. And the documents have to be needed to answer the question; whatever goes beyond the question leaves the exemption. The word "unsolicited", found in many SOPs, does not appear in the law.

The FSA Code for healthcare professionals draws the same line. Under Section 1(3) it does not apply to non-promotional information, including under number 2 correspondence and documents that do not serve advertising purposes and are needed to answer a specific question about a particular medicinal product or digital health application, and under number 5 company-related information including reports on research and development programs. The EFPIA Code excludes the same cases in its scope.

The prohibition before approval: Article 87, Section 3a and Section 15 HWG

Article 87(1) of the Directive obliges Member States to prohibit any advertising of a medicinal product in respect of which a marketing authorization has not been granted under Community law. Paragraph 2 requires all parts of the advertising to comply with the particulars listed in the summary of product characteristics.

In its judgment of May 5, 2011 in Case C-249/09 (Novo Nordisk) the Court of Justice read this as prohibiting statements that contradict the SmPC, not as requiring every statement to be contained in or derivable from it; supplementary statements have to confirm or compatibly specify the particulars and meet Article 87(3) and Article 92(2) and (3).

Section 3a HWG implements this: advertising is prohibited for medicinal products that are subject to authorization and are not authorized or deemed authorized under medicinal products law. Its second sentence extends the prohibition to advertising that refers to therapeutic indications or pharmaceutical forms not covered by the authorization. Pre-launch and off-label thus sit in one section.

The legal consequence is in Section 15 HWG. Whoever advertises contrary to Section 3a commits an administrative offense (subsection 1 no. 1); the fine under subsection 3 goes up to fifty thousand euros. Intentional misleading advertising under Section 3 is a criminal offense under Section 14 with imprisonment of up to one year. Added to that are the consequences under competition law, which are not the subject here.

Self-regulation repeats the prohibition and adds an exception. Section 9(1) FSA Code: advertising for medicinal products subject to authorization is permitted only once they are authorized, and advertising referring to indications not covered is prohibited. Section 9(2) permits, at international educational events, information at exhibition stands on medicinal products not authorized nationally, but only with a statement naming the countries where the authorization exists and that it is lacking nationally.

Article 1.01 of the EFPIA Code says it in one sentence: a medicinal product must not be promoted prior to the grant of the marketing authorization allowing its sale or supply, or outside its approved indications. For the MSL before launch this means: everything said proactively about benefit, efficacy or use of the investigational product has to be measured against the question whether it is designed to promote prescription or consumption.

The hard case is the proactive presentation of unpublished data to an opinion leader. There is no request, so the exemption in Article 86(2) does not hold; there is no authorization, so Section 3a applies as soon as the presentation is promotional. What remains is the evidence that it was scientific exchange without a sales purpose, and that evidence gets harder the closer the launch comes.

Who is a pharmaceutical sales representative: Sections 75 and 76 AMG

The Arzneimittelgesetz does not know the Medical Science Liaison, but it knows the Pharmaberater, and the definition in Section 75(1) is wide: pharmaceutical companies may only commission persons with the expertise under subsection 2 to visit, as their main occupation, members of the health professions in order to inform them professionally about medicinal products. The provision also applies to information given by telephone.

The wording ties in three elements: main occupation, visiting health professionals, professional information about medicinal products. Nothing there speaks of advertising or sales. An MSL who visits investigators and opinion leaders to talk to them about medicinal products meets the elements by the wording, even if the conversations are designed to be non-promotional. Whether practice sees it that way is a legal question that this article does not decide.

The expertise under Section 75(2) is held by pharmacists, graduates of a university degree in pharmacy, chemistry, biology, human or veterinary medicine, pharmacy assistants, technical assistants in these fields and certified pharmaceutical representatives.

The wording names exactly these five fields; a degree in physics, biochemistry or biotechnology is not among them and qualifies only via Section 75(3), recognition by the competent authority of a training that is at least equivalent. For interim staffing this has to be checked before the first visit.

Section 76(1) lays down two duties. In so far as the representative informs health professionals about individual medicinal products, the summary of product characteristics under Section 11a has to be presented. And reports from health professionals on adverse reactions, contraindications or other risks have to be recorded in writing or electronically and communicated to the commissioning company in writing or electronically.

The second duty is the more important one for the MSL because it applies regardless of authorization status. Every adverse reaction report from a KOL conversation has to be recorded and passed on. Article 93(3) of the Directive requires the same of medical sales representatives toward the scientific service, Section 27(7) FSA Code of representatives toward the scientific department, and Article 20.01 EFPIA Code of medical sales representatives "forthwith".

Separating medical from sales: what the texts actually say

The service pages and job descriptions of many companies say that the FSA Code and the EFPIA Code require the MSL to be separated from sales down to reporting lines and targets. The wording of the codes is narrower, and whoever knows it argues more precisely in front of the compliance function and in an audit.

Article 98(1) of the Directive requires the marketing authorization holder to establish, within the undertaking, a scientific service in charge of information about the medicinal products it places on the market. Section 27(5) FSA Code implements this: every company must have a scientific service responsible for all information about its medicinal products that meets the requirements of Section 75(2) AMG.

An express separation of functions is in Section 27(6) FSA Code and concerns the head of the medical department, who is responsible for non-interventional studies: under no circumstances may that person also be responsible for marketing or sales; a separation of functions has to be ensured.

Section 19(2) no. 12 adds to it for non-interventional studies: pharmaceutical sales representatives may be deployed there only for administrative purposes, under the supervision of the head of the medical department, and their involvement may not be linked to advertising for medicinal products. Of MSLs, their reporting lines or their remuneration the Code says nothing at any point.

The EFPIA Code requires in Article 20.01 a scientific service in charge of information about the company's medicinal products and of approving and supervising non-interventional studies, including a medical doctor or pharmacist who approves promotional material before release. The terms "Medical Science Liaison" and "MSL" do not appear anywhere in the Code; the Code knows medical sales representatives and company staff in general.

Section 18.02 draws the same line as Section 19(2) no. 12 FSA for non-interventional studies: medical sales representatives may only be involved "in an administrative capacity", under the supervision of the scientific service, and "such involvement must not be linked to the Promotion of any Medicinal Product". A rule on the head of the medical department like Section 27(6) FSA does not exist in the EFPIA Code.

For the organization it follows: both codes prescribe the scientific service and keep the involvement of representatives in studies apart from promotion; the separation of functions at the top of the medical department is required only by the FSA Code.

That MSLs are not measured on sales targets and do not report to sales is the route by which companies prove that their conversations are not advertising within the meaning of Article 86. It is a practice standard with good reason, but it is no line of a code that one can quote.

Advisory boards and consultancy contracts: Section 18 FSA Code and Article 15 EFPIA Code

Advisory boards are the point where scientific advice and unlawful inducement lie closest together. Section 7(1) HWG prohibits offering, granting or, as a member of the professional circles, accepting gifts and other promotional benefits, with narrowly defined exceptions.

Whether a fee for scientific advice falls under those exceptions, Section 7 HWG does not say expressly; the codes require an actually rendered scientific or professional service and a proportionate remuneration (Section 18(1) nos. 2 and 6 FSA Code, Article 15.02 EFPIA Code) and say how that is to be shown.

Section 18(1) FSA Code permits paid services by healthcare professionals, among them consultancy and participation in advisory board meetings, only for the purpose of supporting healthcare, research or education. Seven criteria hang on that, and each of them is a document in the file of the advisory board.

The contract has to be concluded in writing before the services start and name service and remuneration (no. 1). Before concluding it, the company must have identified and documented a legitimate need for the services; the service has to be a scientific or professional activity for the company, which the Code calls the prohibition of sham contracts (no. 2). Selection follows the need and is made by staff with the relevant expertise (no. 3).

The number of consultants and the extent of the service may not exceed what is reasonably necessary to fulfill the intended tasks (no. 4). The contractual relationship and the services provided have to be documented, the essential documents kept for at least one year after the end of the contract, and the services have to be put to appropriate use (no. 5). Minutes that nobody reads do not meet that last half-sentence.

The remuneration may consist only of money and has to be proportionate to the service; as a reference point the Code names the German medical fee schedule, hourly rates are permissible, expenses reimbursable (no. 6). The contract may not be concluded to influence treatment, prescribing or purchasing decisions or for mere advertising purposes, and that expressly also applies to clinical studies and non-interventional studies (no. 7).

Article 15.02 of the EFPIA Code contains the same criteria in English and adds the formula against which fees are measured in an audit: the remuneration has to be "reasonable" and reflect "the fair market value of the services provided", and "token consultancy arrangements must not be used to justify compensating the HCPs". Under Article 23.03, fees to individual healthcare professionals are disclosed individually under "Fees for Service and Consultancy", separately from expenses.

Two side rules of Section 18 apply in the daily work of an MSL. Under subsection 2, contractual partners have to point to their work for the company in publications and lectures when the subject concerns the company. Under subsection 5, no payment may be made for being prepared to receive a pharmaceutical sales representative or medical device consultant; a fee for the conversation itself is thereby excluded.

Investigator-initiated trials: who is the sponsor

If the company supports a trial that an investigator has initiated, Regulation (EU) No 536/2014 decides the roles. Article 2(2)(14) defines the sponsor as the individual, company, institution or body that takes responsibility for the initiation, for the management and for setting up the financing of the clinical trial; point 15 defines the investigator as the person responsible for the conduct of a trial at a trial site.

Article 71 states that a clinical trial may have one or several sponsors, that a sponsor may delegate tasks in a written contract "without prejudice to the responsibility of the sponsor", and that "the investigator and the sponsor may be the same person".

In an investigator-initiated trial the sponsor role lies with the investigator or, since Article 2(2)(14) also names institutions and bodies, with the investigator's institution, with all duties of the chapter; the company is a third party that provides the investigational product or funds.

Article 72 governs the case in which the company does more. Where a trial has several sponsors, all of them carry all sponsor duties, "unless the sponsors decide otherwise in a written contract setting out their respective responsibilities. Where the contract does not specify to which sponsor a given responsibility is attributed, that responsibility shall lie with all sponsors." Whatever the contract does not assign therefore rests with everyone.

For the MSL function that receives and assesses IIT proposals, two questions follow before any commitment to support. Does the company take responsibility for initiation, management or financing in the sense that it becomes a sponsor or co-sponsor? And does the contract state which duties stay with the investigator, which the company assumes and how safety information flows? Without that allocation, the second sentence of Article 72(1) applies.

Section 18(1) no. 7 of the FSA Code remains alongside: the contract may not be concluded for advertising purposes, and this also applies to clinical studies and non-interventional studies as well as all other studies or data collections. An IIT whose research question nobody in the company can justify scientifically is open to challenge under that sentence, regardless of how the sponsor role is allocated.

What the file has to carry per interaction

From the texts read, it follows what has to be recorded per conversation if the exemption in Article 86(2) and Section 1(5) HWG is to hold. First, the request itself: who asked which specific question about which medicinal product, and when. Second, the answer and the documents, limited to what was needed to answer. Third, the presentation of the summary of product characteristics under Section 76(1), in so far as an authorized product was discussed.

Fourth, every report of adverse reactions, contraindications or other risks, with evidence that it was passed to the scientific service. Fifth, for advisory boards the seven records from Section 18(1): identified need, selection rationale, contract before start, number of participants, fee calculation, minutes and their use, available for at least one year after the end of the contract. Sixth, for investigator-initiated trials the contract allocating the sponsor duties.

This file is not an end in itself. It is the only evidence that a piece of information given before approval was an answer and not advertising, and it does not come into being after the fact. Whoever sets up an MSL function therefore first decides what the note on the request looks like and where the adverse reaction report goes, and only then which opinion leaders will be visited.