Regulatory Issues in Digital Pharmaceutical Communications in the EU--Part 1

The use of eHealth systems and services-defined as healthcare practice using the Internet-offers great potential to enhance patient safety by avoiding medical errors and improving communications, while reducing costs and inefficiencies in areas such as record keeping.¹

Because of this potential to improve health systems, the use of eHealth technology to aid in medical diagnosis and treatment and support pharmaceutical communication will likely become increasingly common. However, before adopting eHealth technology, healthcare stakeholders should carefully consider the risks and identify legal concerns.

This is the first of a three-part series, where we examine the regulatory implications of eHealth systems and services in the EU. We look at the development of digital communication with regard to adaptation of rules relating to pharmaceutical communication in the context of the Internet (part 1). Specific issues associated with the development of collaborative websites with web 2.0 features (part 2) and with the regulation of application software (part 3) also will be covered.

Adapting Pharmaceutical Communication to the Digital Era

The flexibility of digital media provides pharmaceutical companies with new ways to communicate with healthcare stakeholders more rapidly and at reduced costs. For example, digital media expedite delivery of information to the general public regarding adverse reaction warnings or updates to the product leaflet. They also enable pharmaceutical companies to rapidly deliver information about the appropriate use of their products by patients.

For example, two-dimensional barcodes printed on drug packages can now be scanned with a smartphone, giving patients mobile access to updated information about the product or to online support programs. Instructions for use of medical devices can now be provided on an electronic storage medium, such as DVD, supplied with a device; directly displayed by a device fitted with a built-in system; or made available through a website. These new media can help ensure wider access to the information, particularly for blind or partially sighted patients who can benefit from audio instructions or the ability to increase font size on the web or a DVD.

Digital media also provide drug and device manufacturers with new marketing opportunities and are changing the practice of drug promotion. Companies are exploring online marketing as an alternative way to reach physicians or patients. Emerging e-promotional activities include live video visits by sales representatives, online events, electronic sampling and customer service portals for physicians such as updated information on pharmacovigilance. Online visits by medical sales representatives have the potential to greatly reduce costs and facilitate communication with professionals in remote areas.

Although there are many benefits to digital communication by pharmaceutical companies, the use of electronic media for promotional information and advertising as well as non-promotional information raises numerous legal issues.

Digital Advertising

The legal ramifications of pharmaceutical digital advertising depend on whether it is aimed at the general public or at health professionals.

Compliance with Rules on Advertising to the General Public

The flexibility and rapidity of digital communication do not obviate the need to obey the restrictions on drug promotion to the general public, defined as any form of door-to-door information delivery, canvassing activity or inducement designed to promote the prescription, supply, sale or consumption of medicinal products. These restrictions apply irrespective of the method of communication.²

The distinction between advertising and factual informative announcements containing no product claims is not always clear or consistently interpreted. This confusion has resulted in certain restrictions on the ability of pharmaceutical companies to provide information to the public, and also has given rise to situations where the general public is exposed to disguised advertising.³

The European Commission recently issued a proposal for a directive on providing information to the general public about prescription medicinal products that clarifies the distinction between advertising and factual information relating to the product such as the most recent summary of the product characteristics, labeling and package leaflets as approved by the Competent Authorities and information relevant to the proper use of the medicinal products.⁴

Under current European regulation,⁵ attaching a paper leaflet to the medicinal product is mandatory. However, nothing prohibits a drugmaker from providing additional instructions for the use of the product in electronic form, as long as they comply with the rules set up by the directive or European Medicines Agency guidelines relating to readability and clarity.

In contrast, manufacturers of medical devices can provide information about safe and proper use, expected performance and any precautions in electronic instead of paper form.⁶ Nevertheless, users must be given the opportunity to obtain those instructions in paper form upon request.⁷

Except for medical devices, there is no definition of what constitutes the relevant information on the proper use of a medicinal product in the Commission proposal or existing legislation and guidelines.⁶ Such uncertainties entail risks for manufacturers regardless of which media they use to communicate about their products.

The implementation of the proposed regulation relating to advertising is all the more challenging in the context of digital communication, as it is more difficult to ensure that online product information is accessed only by healthcare professionals. Citizens from various countries with diverging rules can access the same websites.

For instance, in Europe, advertising prescription medicinal products to the general public is prohibited, but it is permitted in the US.⁸ Even within the EU, rules regarding whether a drug can be sold over the counter or only by prescription are not entirely harmonized. Therefore, when advertising a medicinal product on the web, companies will have to distinguish different visitors and restrict access by the populations of European countries where the product must be prescribed by a physician.

While a simple warning (e.g., "Intended for US residents only") may be insufficient to properly restrict access to online advertising, pharmaceutical companies can make a website accessible only to a certain group by requiring the user's location, ID or password, or by employing more sophisticated and secure user authentication systems. On this point, France's National Agency for the Safety of Medicines and Health Products has a charter for pharmaceutical companies' online communication that adapts the rules regarding drug advertising on the Internet. It states that access to prescription drug ads should be restricted via the assignment of a personal access code to health professionals (the physician's registry number for the French medical board, for instance).⁹

Adapting Rules on Medical Visits

The use of digital technology, such as smartphones or tablets with access to the Internet or the development of online marketing (E-ADV/E-detailing), makes it easier to provide information that is up-to-date, accurate, verifiable and complete, and in compliance with the rules on visits from medical sales representatives.¹⁰ In particular, Article R.5122-11 of the French Public Health Code requires that, in addition to the summary of product characteristics and classification of the medicine with regard to prescription and delivery, the information given to the doctor must contain the most recently published assessment for the reimbursement of the medicine.

The 2004 Medical Visit Charter signed between the economic committee of health products (Centre for European Policy Studies) and the French pharmaceutical companies association (Les Entreprises du Médicament) allows the use of audio, video or interactive media, provided they are accompanied by a paper document to be handed to the doctor.¹¹

With regard to the prohibition of giving gifts or pecuniary advantages or benefits in kind to persons qualified to prescribe medicinal products, the French High Health Authority (HAS) does not consider audio-visual material such as CD-ROMs or USB keys to be gifts.^12,13Supplying other types of material (i.e., application software) is not seen as a violation of the prohibition of gifts, provided they are inexpensive and relevant to the practice of medicine or pharmacy. Since there is no specific monetary threshold to define what constitutes an inexpensive gift, medical sales representatives are uncertain about what items they are allowed to distribute during their visits.

Regarding online medical visits by company sales representatives, the French charter specifies compliance with requirements including restricted access via a security code provided to health professionals, conformity of the website to the charter, the ability of the medical professionals to access mandatory information about the product during the visit, systematic provision of the information required by Article R. 5122-11 of the French Public Health Code via mail or email after the visit, and education and training of the medical representative according to Article L.5122-11 of the Public Health Code. Also, medical sales representatives should be trained to use digital technology by their employers.¹⁴

Many legal questions remain unanswered, in particular with regard to the supervision of online visits by a qualified, responsible person and traceability of the electronic documents that are distributed to health professionals. Pursuant to the French charter, the pharmacist in charge ensures that only documents whose scientific, medical and economic quality is guaranteed by his or her signature are distributed at the medical visit. How can this be accomplished in the context of online medical visits?

Legal Risks of Digital Communication of Health Information

Communicating health information by electronic means creates specific risks to privacy and security.

Challenges of Communication via the Internet

Online communication of health information is governed by national and EU legislation such as the Electronic Commerce Directive and the Telecommunication Privacy Directive that establish harmonized rules on issues such as the transparency and information requirements for online service providers, commercial communications (that must be identifiable as such) and limitations of liability of intermediary service providers.^15,16

Under Article 8 of the Electronic Commerce Directive¹⁷, regulated professionals such as doctors are permitted to provide online services subject to compliance with professional rules. The directives, however, do not address the specifics of communication on health issues or pharmaceutical products.

The French charter and the Health on the Net Foundation provide some advice regarding confidentiality or transparency requirements for the communication of health and medical information on the Internet.¹⁸ The charter states medical or health information websites must include information necessary to identify the publisher, update information regularly, and distinguish or isolate promotional information from other content. The charter also provides some rules relating to Internet links and banners and bibliographic databases. However, such recommendations are only applied on a voluntary basis and their legal force is limited, as neither the French agency nor the Health on the Net Foundation has the power to adopt legally binding decisions. Moreover, these recommendations are being updated.

Addressing Risk of Diversion, Dysfunction of Electronic Media

Despite their obvious advantages for displaying instructions via the web or other electronic channels, the use of electronic media potentially increases the risk of tampering, dysfunction or display errors. In particular, conducting online visits with physicians, as well as the use of interactive technologies, increases the risk of modification of content, and the risk of off-label promotion, which is illegal in both the EU and the US.^{19, 20} The distribution of supporting technologies with limited storage capacity, use of software with a locked down operating system and restricting website access may help minimize the risk of illegal promotion.

The European Commission regulation of 9 March 2010 addresses the risk of diversion and dysfunction associated with the use of electronic labels.²¹ When information is provided on an electronic storage medium supplied together with the device, or where the device is fitted with a built-in information system, it should also be made available through a website.²² Manufacturers of medical devices shall undertake a document risk analysis to ensure that electronic content is protected from tampering, and back-up mechanisms are in place in the event of a hardware or software fault.^23,24 Finally, manufacturers of medical devices fitted with a built-in system visually displaying instructions for use shall ensure that the display instructions do not impede the safe use of the device, in particular life monitoring or life supporting functions.²⁵

Where the information is provided via a website, the European Commission regulation specifies instructions for use shall be provided in a commonly used format that can be read with freely available software, protected against hardware and software intrusion and provided in such a way that server downtime and display errors are reduced as much as possible. Also, the Internet address displayed shall be stable.²⁶

Manufacturers should undertake a documented risk assessment of impact due to temporary unavailability of the website, or of the Internet in general, as well as the safety measures available to cope with this situation.²⁷Similar rules regarding information relating to the use of medicinal products provided via a website would be useful.

References

1. European Commission. "Digital Agenda for Europe." http://ec.europa.eu/digital-agenda/en/about-health. Accessed 12 December 2012.
2. Directive 2001/83 as amended, Articles 90 et seq.
3. Recital 4 of the Commission amended Proposal COM 2012/48 for a Directive of the European Parliament and of the council amending Directive 2001/83/EC as regards information to the general public on medicinal products subject to medical prescription.
4. Commission amended Proposal COM 2012/48 for a Directive of the European Parliament and of the council amending Directive 2001/83/EC as regards information to the general public on medicinal products subject to medical prescription
5. Title VIIIa (Information to the general public on medicinal products subject to medical prescription) of the amended Proposal for a Directive of the European Parliament and of the council amending Directive 2001/83/EC as regards information to the general public on medicinal products subject to medical prescription.
6. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 1.
7. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 5 (3). http://www.obelis.net/docs/Regulation_207_2012_electronic_instructions.pdf. Accessed 12 December 2012.
8. Op cit 6.
9. Directive 2001/83, Article 88.
10. Direction de l'évaluation de la publicité, des produits cosmétiques et des biocides, Charte pour la communication sur Internet des entreprises pharmaceutiques, mise à jour 2010.
11. Directive 2001/83, Article 92.
13. "Charte de la Visite Médicale." LEEM website. http://www.leem.org/sites/default/files/PDF%207_0.pdf. Accessed 12 December 2012.
14. Directive 2001/83, Article 94.
15. "Questions Reponses Relatives à la Certification de la Visite Medicale." Haute Autorité de Santé. http://www.has-sante.fr/portail/upload/docs/application/pdf/questions_reponses_vm_02_2008.pdf. Accessed 12 December 2012.
16. Directive 2001/83, Article 93. "Medical sales representatives shall be given adequate training by the firm which employs them and shall have sufficient scientific knowledge to be able to provide information which is precise and as complete as possible about the medicinal products which they promote".
17. "Directive 2000/31/EC of the European Parliament and of the Council of 8 June 2000 on certain legal aspects of information society services, in particular electronic commerce, in the Internal Market." Eur-Lex website. eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32000L0031:En:HTML. Accessed 12 December 2012.
18. Directive 2000/31.
19. Directive 2002/58/EC of the European Parliament and of the Council of 12 July 2002 concerning the processing of personal data and the protection of privacy in the electronic communications sector (Directive on privacy and electronic communications).
20. Health on the Net Foundation. http://www.hon.ch/home1.html. Accessed 12 December 2012.
21. Directive 2001/83, Article 91.
22. FDCA § 505(a), 21 U.S.C.§ 355(a): "No new drug may be introduced or delivered for introduction into interstate commerce without a new drug application" 63 Fed. Reg. 31,143, 31,145 (8 June 1998).
23. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices
24. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 7 (1).
25. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 4(e).
26. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 4(f).
27. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 5 (6).
28. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 7(2).
29. Commission Regulation EC 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, Article 4(h).