Marketing, Manufacturing, Packaging & Labelling, Advertising
Tackling the big issues around marketing, manufacturing, packaging & labelling, and advertising in Latvian pharma. Prepared in association with TGS Baltic, a leading law firm in Latvia, this is an extract from The Pharma Legal Handbook: Baltics, available to purchase here for USD 99.
1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?
Please refer to Question 3 in Regulatory, Pricing and Reimbursement overview.
2. What is the authorization process for the marketing of generic versions of these products?
A person seeking marketing authorization must prove that the medicinal product is a generic medicinal product of a reference medicinal product, which is or has been authorised for not less than 8 years in an EEA state or in the Community, or that the active substance(s) within the formulation of medicinal products in a EEA Member State is (are) widely used in medicine in the formulation of already registered medicinal products for at least 10 years with a recognised efficacy and acceptable safety level.
3. What are the typical fees for marketing approval?
Please refer to Question 4 in Regulatory, Pricing and Reimbursement overview.
4. What is the period of authorization and the renewal process?
Please refer to Question 3 in Regulatory, Pricing and Reimbursement overview.
5. What are the requirements, if any, for post-approval pharmacovigilance?
HCP, pharmacist, and patient are under obligation to report side effects to the SAM or to the marketing authorization holder.
The marketing authorization holder has the following obligations:
- to ensure the establishment of a pharmacovigilance and a quality system;
- to carry out scientific evaluation of information and take appropriate risk minimization measures;
- to appoint a QPPV on a permanent basis, who shall reside and operate within the EU and shall be responsible for the establishment and maintenance of the pharmacovigilance system;
- to nominate a local person responsible for pharmacovigilance, who resides and works in Latvia;
- to maintain and make available a copy of the pharmacovigilance system master file within 7 (seven) days following a request from the EMA or the SAM;
- to ensure establishment and operation of a risk management system with regard to all medicinal products, with certain exceptions;
- to monitor the outcome of the risk minimization measures;
- to regularly update the risk management system and monitor pharmacovigilance data;
- to regularly perform audit of the pharmacovigilance system, record the main findings of the audit in the pharmacovigilance system master file and ensure that basing on the audit findings an appropriate corrective action plan is prepared and implemented;
- to record all serious and non-serious suspected adverse drug reactions observed in any of the EEA Member States or in third countries;
- to submit the reports (serious reactions no later than 15 days after receiving the information; non-serious reactions – no later than 90 days after receiving the information) to the EU database of adverse drug reaction reports (hereinafter Eudravigilance database);
- to ensure the availability of adverse drug reactions in the Eudravigilance database;
- to accept and review reports from the SAM, HCPs, pharmacists, including reports sent by a parallel importer and parallel distributor of medicinal products, and patients regarding suspected adverse drug reactions;
- to establish written procedures in order to obtain accurate and verifiable data for the scientific evaluation of suspected adverse drug reaction reports, as well as additional information relating to a suspected adverse drug reaction report;
- to collaborate with the EMA and the competent authorities of the EEA Member States in the detection of duplicates of suspected adverse drug reaction reports;
- to submit periodic safety update reports (PSUR);
- to submit to the SAM application for amendments to the marketing authorisation documentation including an updated summary of product characteristics and package leaflet in accordance with the normative acts regarding procedure for marketing authorisation of medicinal products;
- to inform the EMA and the SAM, if there are new risks, the current risks have changed, or there are changes to the risk-benefit balance;
- to inform the SAM as soon as possible, but no later than 15 days after receiving or becoming aware of information regarding suspected serious adverse drug reactions.
Parallel importer has the following obligations:
- to submit the adverse drug reaction report to the SAM and the marketing authorisation holder as soon as possible, but no later than 2 (two) days after receiving the report,
- to inform the author of the adverse drug reaction report that adverse drug reactions must be reported directly to the SAM or the marketing authorisation holder.
6. Are foreign marketing authorizations recognized?
Yes, marketing approval may be received following the mutual recognition procedure, which is based on the recognition of a pre-existing national marketing authorisation by one or more EU countries, or the decentralised procedure, where the application for marketing authorisation is submitted simultaneously in several EU countries, one being chosen as the “Reference Member State”.
7. Are parallel imports of medicines or devices allowed?
Yes. Parallel import of medicinal products is permitted exclusively, if the parallel importer has received a valid permit issued by the SAM. The parallel importer shall inform on its intention to start distribution of the parallelly imported products in Latvia:
- the registration owner (holder of sales permit);
- the SAM;
- the owner of the brand of medicinal product.
8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?
It is prohibited to supply, offer, or promise benefits in kind to employees practicing in state and municipal health care institutions (e.g. doctor, nurse, clerk in a state or municipal health care institution), unless these benefits a) can be used in the medical practice, and b) do not exceed a threshold of EUR 10 (Article 23 of Cabinet Regulation No.378)
It is prohibited to supply more than 4 samples for each healthcare professional per year (Article 27 of Cabinet Regulation No.378).
If exhibitions of medicinal products, seminars, conferences, congresses, competitions, and other events related to the advertising of medicinal products are organised, the event organiser must inform the Health Inspectorate thereof no later than 7 days before the event by delivering the event programme and indicating the place and time of the event activities, the organisers and sponsors of the event, participants, intended type of advertising and other information related to medicinal products, as well as the persons responsible for advertising medicinal products. Representation expenses for events with professional and scientific orientation must be subordinated to the main purpose of the event, and they must be applied only to specialists.
Pharmaceutical products may be manufactured only by a legal entity that holds a manufacturing licence (Licence) issued by the Latvian SAM.
9. How is the manufacturing of medicines and devices regulated and by which agencies?
A legal entity seeking a licence must:
- specify the pharmaceutical forms, the location where they will be manufactured and controlled, as well as the particular acts to be performed with medicinal products;
- have at its disposal sufficient and appropriate premises, technical equipment and control facilities complying with the requirements established by law;
- enter into a contract with a person for fulfilling the duties of a qualified person responsible for manufacture and (or) import and;
- comply with other requirements set by law.
10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the U.S. Food & Drug Administration and/or the European Medicines Agency?
Pharmaceutical products must be manufactured in compliance with the Good Manufacturing Practice standards.
11. What is the inspection regime for manufacturing facilities?
In Latvia, SAM is responsible for inspecting manufacturing sites located in its own territories.
Manufacturing sites outside the EU are inspected by the national competent authority of the Member State, where the EU importer is located, unless a mutual recognition agreement (MRA) is in place between the EU and the country concerned. If the MRA applies, the authorities mutually rely on each other’s inspections. If products are imported directly into more than one Member State from a manufacturing site outside the EU, there may be more than one national competent authority responsible for inspecting it. EMA facilitates cooperation between the authorities concerned in supervising the site.
EU competent authorities plan routine inspections following a risk-based approach, or if there is suspicion of non-compliance. The SAM may agree on specific dates on inspection 10 (ten) days in advance for marketing authorization or perform on-site visits at any time during supervision period.
12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?
Yes, the SAM may initiate joint inspections based on request of the EMA or agency of medicines based in the EU, EEZ.
13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?
In pharmacies it is required to store medicines separately from other goods, not to place medicines in the customer servicing area, as well as not to place prescription medicinal products in a location visible to customers. Hospitals are required to store medicines in a separate closed type pharmacy, or, if such is unavailable, in separate closed premises.
The storage of medical devices is not intensely regulated. The main requirement during storage is to implement the instructions of the manufacturer so that the device, its qualities and safety parameters are not adversely affected.
14. What information must be included in medicine and device labelling?
The following mandatory particulars are required on the labelling:
- name of the medicinal product followed by the strength.
- invented name not liable to confusion with the common name;
- common or scientific name accompanied by a trade mark or the name of the marketing authorization holder;
- statement of the active substances
- pharmaceutical form and contents;
- list of excipients;
- method and route of administration;
- special warning that the medicinal product should be stored out of reach and sight of children;
- expiry date;
- special storage precautions
- special precautions for disposal of unused medicinal products or waste materials from medicinal products (if necessary), as well as the message that the unused medicinal product shall be returned to the pharmacy (if the medicinal product requires special conditions for destruction);
- name and address of the holder of the marketing authorization for the medicinal product, and the name of the representative of the marketing authorization, if the one is appointed;
- product marketing authorization number in the Latvian Drug Register, or the relevant marketing authorization number granted by the European Medicines Agency, if the medicinal product is granted the marketing authorization following the centralised procedure according to the European Parliament and Council Directive (EC) No. 726/2004 of 31 March 2004 that establishes the Community procedures for marketing authorization and monitoring of human and veterinary medicinal products and sets up the European Medicines Agency (hereinafter Regulation (EC) No.726/2004);
- manufacturer’s batch number. In case the medicinal product has been re-packed or re-labelled, re-packaging or re-labelling batch number as well;
- for OTC products: instructions on the use;
- name and address of the manufacturer (re-packer or re-labeller) of the medicinal product, where the medicinal product has been re-packed or re-labelled. For medicinal products imported in parallel import procedure, the name and address of the holder of the distribution permit for medicinal products imported in parallel.
The following information shall be indicated on the packaging of a medical device:
- name of and address of the manufacturer or authorized representative thereof (if the manufacturer has not registered commercial activity in any EU state);
- name of the medical device, purpose, and detailed information for identification of the device;
- note “Sterile”, if the device is sterile;
- type and manufacturing (batch) number of the medical device;
- date of expiry of the medical device, indicating the year and month, before which the medical device may be used safely, if the medical device has a limited use period (or the life cycle of the device, if the medical device has a limited life cycle)
- identification code of the trial subject (if the medical device is intended for one trial subject);
- note “custom made” if the device is custom made
- conditions for storage of the medical device;
- special operation conditions;
- identification number of the trial;
- methods of use and routes of administration of the medical device;
- given name, surname of the investigator;
- warnings or precautionary measures;
- indication whether the device incorporates human blood, a human blood component, derivatives of human cells or tissues.
15. What additional information may be included in labelling and packaging?
The information can be additionally stated in any other language, provided it does not contradict to the information in Latvian.
16. What items may not be included in labelling and packaging?
Any information, which is not impartial or objective, and which does not provide misleading or exaggerated qualities of the medical product.
17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?
No specific rules exist in relation to marketing and advertising of medical devices.
Medicine ads aimed at HCPs may be placed only in scientific and informative press publications for specialists or in specially prepared advertising materials, which might not be distributed to the rest of the public.
It is prohibited to advertise medicinal products (except vaccines) to the general public: prescription products, products containing doping substances psychotropic or narcotic substances or analogues thereof and having high pharmacovigilance risk; and products, the purchase price whereof is partly or fully covered from the State budget resources. Manufacturers must not distribute medicinal products to the general public for promotional purposes.
Advertising must include at least the following information:
- the name of the medicinal product, as well as the common name specified in laws regarding labelling of medicinal products and the requirements to be met for the instructions for use of medicinal products, if the medicinal product contains only one active substance;
- information required for correct use of the medicinal product;
- a clear and legible invitation to carefully read the instructions for use or the relevant information on the packaging;
- an invitation to consult a physician or pharmacist regarding use of the medicinal product; and
- the warning “unreasonable use of medicinal products is harmful to health”.
Advertising (both to professionals and the general public) of products not authorized in Latvia or lacking a valid marketing authorization or not authorized according to the centralized authorization procedure of the European Medicines Agency is prohibited. Also prohibited is advertising medicinal products offered as a gift or compensation for the purchase of goods or receipt of a service or where a gift is offered for purchase of medicinal products (including an offer associated with the purchase of medicinal products to purchase medicinal products, other goods, or services at a discount).
18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?
Yes, subject to limitations. The post message sender must be clearly identified.
The following legal entities are allowed to receive / dispatch medicines by mail:
- a special permit (licence) holder for opening (operation) of a wholesale enterprise of medicinal products (issued by the SAM);
- a special permit (licence) for manufacturing or import of medical products granting the right of wholesale distribution to the holder;
- a wholesaler / manufacturer of medicines licensed in the EU / EEZ;
- a certificate on registration of the medical institution in the Register of Medical Institutions issued by the Healthcare Inspection, if medicinal products are received by a medical institution (doctor’s practice).
Natural persons (does not apply to drugs and psychotropic substances):
- are entitled to import or to receive by mail medicinal products for personal use;
- the dispatcher of products must be clearly identifiable;
- the dispatcher of products must have the relevant rights for distribution of medicinal products;
- the amount of either imported or received medicinal products on a single occasion may not exceed the amount required for 12-months use;
- submit a prescription or a copy thereof certified by a pharmacy issuing medicinal products, or by a document issued by another medical institution.
19. What are the restrictions and requirements for electronic marketing and advertising via email, by Internet, social media, and other channels?
Certain requirements prohibit sending of commercial notices via email without customer consent. If products prohibited from being advertised to the general public are advertised on the internet, the advertiser or disseminator of the advertising must ensure accessibility of information only to specialists.
It is allowed to distribute only non-prescription medicinal products on the internet.
The pharmacies distributing medicines on the internet have the following main requirements:
- provide a round-the-clock contact services for customers, and to provide free-of-charge advice and information concerning medicinal products;
- create a website, which should be available to customers without interruption on a round-the-clock basis and comply with requirements concerning advertising rules;
- pharmacy retailer trading medicinal products on the internet is under obligation to receive a special permit (licence) and guarantee necessary server and communication channel capacity;
- retailer guarantees that the website information is true and correct and informs the SAM and the Health Inspectorate on the domain title, electronic mail address, internet website address, as well as on the alterations made.
20. May medicines and devices be advertised or sold directly to consumers?
Yes, subject to certain limitations (see p. 17 above). Medicines and devices may be sold in pharmacies only. OTC products may be sold in the internet. It is permitted to advertise non-prescription medicines to the general public. It is prohibited to advertise to the general public the pharmaceuticals, the price of which is partly or entirely compensated from the state budget.
21. How is compliance monitored?
The Health Inspectorate monitors compliance with the relevant advertising laws and imposes penalties. Any party may complain (further status of complainant will depend on the complainant’s legitimate interest). Anonymous complaints are not considered but ordinarily stimulate the inspectorate to investigate the matter ex officio.
22. What are the potential penalties for noncompliance?
The inspectorate may impose a penalty for violations of relevant advertising rules up to EUR 700 for individuals and from EUR 400 to EUR 14,000 for legal entities.
The Health Inspectorate may also issue a warning (setting a certain term for the elimination of violations) to the medical company. If the violations are not eliminated, the inspectorate may close down the operation of the company.