What post-market monitoring mechanisms are in place to ensure the ongoing safety and efficacy of medicinal products after marketing authorisation has been granted?
There are several post-market monitoring mechanisms associated with marketing authorisation that are regulated within various regulations. Having said that, the main obligations of a marketing authorisation holder before the Pharmaceuticals and Medical Devices Agency regarding the possessed authorisation include:
- manufacturing of the product as per agency specifications and scope of the approved marketing authorisation;
- making approval submissions to the agency for every change required for considering scientific developments, manufacture and control of products in well-accepted methods;
- updating the summary of product characteristics and instructions for use, if necessary;
- fulfilling essential responsibilities within the scope of pharmacovigilance practices (although pharmacovigilance services can be outsourced, the marketing authorisation holder still remains responsible);
- making the products available in the market; and
- complying with all applicable laws and regulations in its activities (eg, promotional operations).
What data protection issues should be considered when conducting pharmacovigilance activities?
Pursuant to the Regulation on the Safety of Medicines, when conducting pharmacovigilance activities, the identification and address of the patient and the healthcare provider notifying the Pharmaceuticals and Medical Devices Agency will be kept confidential within the notifications. This information will not be declared to third parties, other than the Pharmacovigilance Centre personnel, without their consent. The marketing authorisation holders, health institutions and organisations and healthcare providers must comply with these confidentiality principles.
The amended Personal Health Data Regulation includes additional requirements for data protection regarding the conduct of pharmacovigilance activities.
Pricing and reimbursement
Are there rules governing the pricing of medicinal products in your jurisdiction?
The rules governing the pricing of pharmaceutical products are regulated by the Decree Regarding Pricing of Pharmaceuticals and the Pricing Communiqué which was amended on September 29 2017. All pharmaceutical products must obtain a price by making a submission to the Pharmaceuticals and Medical Devices Agency, according to the decree and communiqué. According to the decree and communiqué, the Turkish pricing system consists of various pricing rules based on reference pricing and the applicant's declarations as to the reference prices in five countries (France, Spain, Italy, Portugal and Greece) that are taken into account with regard to the general principles set out. The applicant must notify the agency of subsequent changes to the declared prices within the notification periods regulated by the communiqué. However, the agency may revise the price of a product ex officio if, as a result of its own investigation, it spots changes in the pricing conditions.
What is the structure for state reimbursement of medicinal product costs?
Under the state reimbursement of medicinal product costs, if the marketing authorisation holder obtains a reimbursement approval from the Social Security Institution following issuance of the sales permit, the Social Security Institution may be one of the payers which would purchase the product on the discounted reimbursement price instead of the initial price approved by the Pharmaceuticals and Medical Devices Agency. The Social Security Institution has strict reimbursement rules as a result of certain concerns regarding the public healthcare budget, and the reimbursed price of a product which is met by the Social Security Institution from the public funds is therefore materially lower than the initial agency-approved price. Still, since the Social Security Institution is the main buyer in the healthcare system, marketing authorisation holders mostly do not prefer to enter the market unless they have obtained reimbursement approval from the Social Security Institution.
Advertising and labelling
How is the advertising of medicinal products to healthcare professionals and the general public regulated in your jurisdiction?
Advertising pharmaceutical products to the general public is strictly prohibited in Turkey; whereas promotion of licensed pharmaceuticals to healthcare professionals is allowed and regulated under the Promotion Regulation. According to the regulation, allowable promotional activities include, without limitation, the following:
- visits to healthcare professionals;
- the organisation of scientific or product promotion meetings;
- the distribution of free samples;
- certain symbolic reminder materials; and
- printed materials relating to the products.
Do any special rules apply to online advertising of medicinal products?
Online advertising of medicinal products via the Internet or any other electronic environment is strictly prohibited in Turkey.
What are the packaging and labelling requirements for medicinal products?
As part of legislative harmonisation the Turkish Labelling Regulation has been abrogated and the Regulation on Packaging and Labelling of Human Medicinal Products was introduced on April 25 2017. The Regulation on Packaging and Labelling of Human Medicinal Products provides the rules in relation to the outer and inner labels of a pharmaceutical product. Accordingly, the necessary information (eg, name, dosage, form and amount of the product, storage conditions and manufacturer's name and marketing authorisation number) will be provided on the outer packaging in a legible, understandable and non-erasable way. Moreover, a summary of product characteristics and instructions for use in the format required and approved by the Pharmaceuticals and Medical Devices Agency must also be included within the packaging.
How is the promotion of off-label use regulated?
In principle, the promotion of off-label use is prohibited in Turkey, as promotional activities must be in line with the approved product indications. However, there are certain exceptions, such as the promotional activities conducted during the international congresses held in Turkey or the provision of information directly by a medical liaison officer on the written request of a physician, dentist or pharmacist.
Relations with healthcare professionals
Gifts and incentives
What rules apply to the provision of gifts, discounts and other incentives to healthcare professionals?
Gifts to healthcare professionals or organisations are prohibited in Turkey. However, it is possible to distribute certain promotional materials that are strictly defined in the Promotion Regulation, including:
- symbolic reminder materials;
- printed materials containing sufficient information on the product;
- films and slides, visual and aural materials;
- materials aiming at patient education; and
- free samples.
Individual donations or grants must not be provided to healthcare professionals; however, marketing authorisation holders may donate to certain healthcare organisations by satisfying certain conditions under the Promotion Regulation. Marketing authorisation holders may also support healthcare professionals for attending a domestic or foreign scientific meeting by covering registration expenses, accommodation and transport. In such cases, the marketing authorisation holder must conform to the Promotion Regulation by obtaining the relevant consent and notifying the Pharmaceuticals and Medical Devices Agency regarding such sponsorship. All value transfers exceeding 10% of the monthly gross minimum wage (including value added tax) are required to be made by obtaining a specific consent from the relevant healthcare professional and disclosing the transfer to the agency.
How can a liability claim for a defective medicinal product be brought?
Given that there is no specific regime regarding the liability of pharmaceutical products, the general doctrinal grounds on product liability will be implemented in the event of a defective medicinal product. Regarding general liability principles, liability may be formed on either a contractual or non-contractual basis. Contractual claims could be initiated under the Law on Obligations and the Law Regarding Protection of Consumers based on the seller's failure to perform his or her obligations completely or duly or due to a defective product. On the other hand, non-contractual liability may arise from several grounds, including:
- tort liability;
- employer's liability;
- danger liability; and
- the liability arising from the Law on Preparation and Implementation of Technical Legislation Regarding Products.
Some of these liability grounds are fault-based and some are strictly liability based, depending on the specialties and factors.
Which parties can be held liable for a defective medicinal product?
In case of a defective medicinal product, the liable parties may differ in accordance with the grounds of claimed compensation and whether the responsible party is at fault. Even though the party accountable for the liability for pharmaceutical products is potentially the manufacturer, depending on the circumstances of the case, the marketing authorisation holder, seller or importer may also be held liable.
What remedies are available to successful claimants?
Successful claimants may claim for both pecuniary and immaterial damages arising from pharmaceutical products. Even though liability on the grounds of materialised damages is commonly seen in practice, the liability of the manufacturer may have arisen from pharmaceuticals that are suitable for generating serious or continual damage, depending on the features of the pharmaceuticals.
Exclusion and limitation
On what grounds can liability be excluded?
First, the manufacturer must issue the recovery proofs as a defence for liability arising from the pharmaceutical products. For instance, in case of employer liability, the manufacturer may claim that it paid the required attention to prevent the damage, giving instruction on the issue and inspecting the employee. Second, it is also possible to claim that the connection of causation is broken down. In relation to the development of risk defence, in case the manufacturer proves that all the requirements are satisfied within the development process, he or she may not be held responsible for defects not discoverable in the existing scientific knowledge in Turkey.
What preventive steps can be taken to limit liability?
As preventive steps, in order to limit liability, companies must provide qualified medicinal products pursuant to the product's specifications and approvals issued by the Pharmaceuticals and Medical Devices Agency and ensure the required storage and distribution conditions. In addition, considering that the promotion of medicinal products to healthcare providers is essential in order to clarify a product's effects, companies should consider ensuring that the promotion is performed with explicit accuracy and in detail in order to prevent indirect liability from being triggered by incorrect prescriptions or treatment.
Compliance and enforcement
What measures are in place to enforce the laws governing medicinal products?
In order to enforce the laws governing medicinal products, the most common enforcement measures are administrative and financial penalties (eg, suspending marketing authorisations, banning promotional activities or imposing administrative fines). Moreover, as per the Law on Preparation and Implementation of Technical Legislation Regarding Products and its secondary legislation, in case of an unsafe product, various penalties – namely, prohibition of placing the product on the market, recalling the product from the market or removing the products from the market partially or completely – can be imposed against manufacturers and distributors. The authority may also order the publication of the decision regarding the unsafe product by announcing to the public details of the unsafe product and the relevant measures imposed by the authority.
What mechanisms are in place to combat bribery, fraud, collusion, counterfeiting and other dishonest practices in the pharmaceutical sector?
The mechanisms and regulations combating dishonest practices are performed under different frames. For instance, the Promotion Regulation includes certain provisions against activities which may be interpreted as bribery or dishonest practice in the pharmaceutical sector. In particular, the recently introduced rules on disclosure of value transfers to the Pharmaceuticals and Medical Devices Agency are expected to increase transparency and compliance within the sector. Internally applicable company standard operating procedures and certain industry rules also force pharmaceutical companies to pay the utmost attention to avoiding dishonest practices.
Another mechanism which aims to reduce the likelihood of counterfeit medicinal products is the Pharmaceutical Tracking System. Within such a system, all domestic and imported products can be pursued during their entire life cycle, starting from the manufacturing or importation, through to placing the product on the market and access by the end user. Moreover, the Ministry of Health and security forces conduct several activities to identify and capture individuals or organised groups involved in counterfeiting or smuggling pharmaceutical products. In general, actions arising from such dishonest practices may constitute a crime within different Turkish laws.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.