Marketing, Manufacturing, Packaging & Labeling, Advertising
All about marketing, manufacturing, packaging & labeling and advertising in Uruguayan pharma. Prepared in association with FERRERE, a leading law firm in Uruguay, this is an extract from The Pharma Legal Handbook: Uruguay, 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?
Please refer to Question 3 in Regulatory, Pricing, and Reimbursement Overview.
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 5 in Regulatory, Pricing, and Reimbursement Overview.
5. What are the requirements, if any, for post-approval pharmacovigilance?
After the creation of the Pharmacovigilance National System by Ordinance No. 798/2014, Laboratories must notify the Pharmacovigilance Unit of the MSP of the identified events (Adverse Drug Reactions -ADR-, Medication Errors -ME- and Events Supposedly Attributable to Vaccination and Immunization -ESAVI-):
- Within 24 hours, in the event of death or risk that involves a large number of persons. Communication must be immediate with the aim of implementing the corresponding actions early;
- Within 48 hours at the most, in those cases of severe ADR or ESAVI, which do not imply a greater population risk;
- Within a maximum term of 15 business days, in all other cases which do not meet the criteria referred to above.
Likewise, Laboratories must:
- Report regularly and when requested by the Pharmacovigilance Unit.
- Enter in a database all notices received.
- Develop methods to obtain early warning signs.
Laboratories must appoint a responsible person for Pharmacovigilance who shall be the valid speaker before the MSP.
6. Are foreign marketing authorizations recognized?
Yes. Foreign marketing authorizations are recognized and required (as mentioned in Question 3 of Regulatory, Pricing, and Reimbursement Overview.) to register products. Although foreign market authorizations speed-up the registration process they do not avoid the need to go through the registration process and to submit all documents indicated in Question 3 of Regulatory, Pricing, and Reimbursement Overview.
7. Are parallel imports of medicines or devices allowed?
No. A product which is imported to Uruguay must be registered, except in the case of health emergency or “compassionate use” (express authorization of the MSP regarding unregistered products requested by patients and prescribed by their treating physicians).
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?
In Uruguay there are no restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for individual private medical practitioners.
However, article 198 of Law 18,996 states that: “The National Resources Fund shall require persons financially or technically related to said body to declare any conflicts of interest that may arise in connection with the sale, production, financing or use of certain technologies, devices, medical acts or drug products.”
The FNR requires medical practitioners to fill out an online form for declaration of conflicts of interest, which acts as a sworn statement.
The “declaration of conflicts of interest form”, with which the FNR regulates the provisions of article 198, establishes that:
- The potential conflict of interest exists regardless of whether the medical practitioner considers that these relationships have influence over their scientific opinion or their commercial or financial performance. In this sense, whenever drugs, products or services provided by the FNR are prescribed, the declaration must be filed, irrespective of the subjective criterion of each professional.
- Potential conflicts of interest can be: i) personal: they imply direct personal benefits such as fees or other compensation in favor of the medical practitioner, their spouse or their children; ii) non-personal: involving funding for a department or unit to which the medical practitioner belongs, even if this funding or benefit is not received directly (e.g. aid to create units or departments, support for hiring personnel, research funding, etc.)
- Any relation that involves receiving financial support for attending meetings and conferences (registration, travel grants, etc.) or being employed or providing services to a pharmaceutical company or entity that supplies medical devices or services to the FNR must also be declared.
On the other hand, the Anticorruption Act No. 17,060 and Decree 30/003 expressly prohibit government official (e.g. medical practitioners from public health institutions) from engaging in the following conducts, among others:
- having a relationship with companies who submit bids in tenders of the institution they work at;
- being involved in government contracts when related by family to the contracting parties;
- receiving money, gifts, benefits, favors or other advantages, for his/herself or for others, for doing, accelerating, delaying or omitting acts pertaining to the government’s official position, or for an act already performed;
- intervening in decisions on matters in which s/he has participated in a technical capacity;
- being an employee, advisor, auditor, consultant, partner or director of individuals or public or private legal entities subject to oversight of offices to which the government official pertains. Government officials are likewise prohibited from receiving retributions, commissions or fees of any kind whatsoever from such persons. The prohibition extends to all contracting of services or works performed at the request of the overseeing Administration, by international organizations or by execution of projects by third parties. This applies to government officials who hold senior direction, inspection or advisory positions.
The following are permitted:
- travel and stay expenses received from governments, educational institutions or nonprofit entities, to give talks, courses or academic or cultural activities, or participate therein, provided same is not incompatible with the government official’s functions or prohibited by special rules;
- reasonable gratifications received on the occasion of traditional holidays in accordance with conditions of accepted use and custom.
9. How is the manufacturing of medicines and devices regulated and by which agencies?
Please refer to Question 1 in Regulatory, Pricing, and Reimbursement Overview.
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?
Yes, local manufacturing requirements are compatible with GMPs. However, the MSP is currently applying the 37th report of the World Health Organization which is not the latest report issued by said organization.
11. What is the inspection regime for manufacturing facilities?
MSP is the authority responsible for inspecting manufacturing facilities with full powers. In practice, the first inspection is planned and previous notification of the inspection date is given to the manufacturer. Other inspections could take place in a “surprise” regime to evaluate:
- compliance of the facilities with GMPs and standard operating procedures;
- whether activities do not exceed the limits set by the authorization and do not differ from those activities which are authorized;
- performance of validation analysis of the manufacturing processes and systems involved.
12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?
There are no specific regulations on this matter.
13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?
Despite the fact that there are no specific regulations regarding all storage, warehousing and packaging requirements of pharmaceutical products, Decree 521/984 sets forth the facilities’ requirements of public or private industrial establishments. The Decree clarifies that such requirements should be deemed to be generic and minimum and that other conditions for approval of facilities and operations of establishments may be determined. Likewise, Uruguay adopted through Decree 440/016 the Good Manufacturing Practices for Pharmaceutical Products, Report 37 of the World Health Organization, so such guidelines would also be applicable.
In this sense, establishments must operate in facilities built with adequate materials and located in such a way that they allow for adequate operability, easy cleaning, maintenance and flow of materials.
They should be connected to the public water supply network and/or have a personal water supply source regularly analyzed and approved in accordance with regulations on potable water. They should have water storage tanks as well as the necessary equipment to ensure the water quantities to be used in the manufacturing of pharmaceutical products, and analysis and tests made should be documented.
Walls should be tiled, oil-based epoxy painted or similar up to two meters height, angles should be sanitary and convex. Surfaces of warehouses and other facilities not assigned to manufacturing should be capable of being bleached.
Paving or other cladding of the floor should be solid and flat and slippery so as to make cleaning easy.
In those places in which operations may cause floor moisture, there should be adequate sewers or drains.
Facilities must count with adequate space for the installation of the necessary equipment and tools.
Facilities must have and ensure: a) direct access to public streets; b) adequate ventilation and lighting; c) equipment for the control of physical and biological conditions when required for manufacturing; d) adequate water filtration in manufacturing areas when necessary; e) extraction systems close to dusty operations which eliminate all contamination risks; f) separate operating systems for the handling of highly active allergenic substances.
Facilities must have sewage, entry, storage and fluid distribution conditions, elimination of waste products which ensure hygiene and avoid the risk of product, personnel and environmental contamination.
Industrial establishments using laboratory animals must have adequate accommodation and space, separate from manufacturing and storage areas.
If within one same establishment tasks other than the manufacturing of drugs are undertaken, these tasks must be performed in such a way as to avoid cross-contamination. Administration, storage and sale of products and personnel’s break spaces must be separated and isolated from manufacturing places.
Operations must be carried out within industrial areas specifically defined and individualized for the administration and reception of public, as well as for: a) storage and quarantine of raw materials and packaging materials; b) storage of approved materials; c) storage of semi-manufactured products; d) storage of rejected materials before disposal in order to avoid their use; e) simultaneous manufacturing, fractioning and packaging operations in which special conditions require so; f) keeping pharmaceutical products quarantined before being released; g) storage of pharmaceutical products after approval; h) performance of all quality control operations; i) in the case of aseptic products, areas must be isolated, conveniently installed and controlled and operate with an adequate methodology which ensures that the products manufactured therein are free of contaminating agents. Special cares regarding clothing, equipment, entry of sterile air, positive air pressure, cleaning and sanitizing are required.
Industrial establishments must comply with the following regulations: a) keeping all facilities clean and in good state of preservation; b) keeping all facilities free of waste, insects and rodents; c) preparing detailed cleaning proceedings in writing; d) only using those cleaning materials which do not cause contamination of products, equipment and packaging material.
14. What information must be included in medicine and device labelling?
Labelling of products must be in Spanish and varies depending on the product:
Decree 324/999 states that labeling of drugs (cases, packaging and prospectus) must contain, among others:
- name of the pharmaceutical product;
- pharmaceutical form;
- preparation for sale and content;
- instructions in relation to: route of administration; instructions; dosage; contraindications; collateral, adverse, undesirable, harmful or toxic effects;
- expiration date;
- category regarding consumption;
- name of the manufacturing establishment and/or import representative;
- registration number of the establishment and registration number of the drug;
- batch number;
- storage and preservation precautions;
- name of the responsible technical director.
In addition to the aforementioned requirements, Decree 38/015 states that biosimilars must be identified as such. The biosimilar’s prospectus information must be as similar as possible to that of the reference biological, in particular as regards dosage and safety information. If the similar has less information than the reference product, express mention of this fact must be included in the prospectus.
For its part, the labelling of medical devices regulated by Decree 3/008 must contain, among others:
- name of the product and content of the packaging;
- batch number: if appropriate, manufacturing date and term of validity or date before which it must be used;
- name and address of manufacturer and importer and country of origin;
- egistration number of the product before the MSP and name of the responsible technical director;
- instructions for use;
- date of sterilization (if applicable), method and expiration;
- conditions for storage, preservation and/or handling and its condition as a reusable product, if applicable;
- any warning and/or precaution which must be followed.
15. What additional information may be included in labelling and packaging?
It is possible to formally ask the MSP to allow other information. MSP has discretionary powers to allow the inclusion of additional information depending on the product, category, etc.
16. What items may not be included in labelling and packaging?
MSP has discretionary powers to allow or not certain items depending on the product category, etc.
MSP will not allow any information which is wholly or partially false or which in any other way, even due to the omission of essential information, might be misleading for the consumer regarding the nature, quantity, origin, etc. of the product. It is also not permitted to register drugs with names directly referring to the illness or to include images promoting the use of products by children, among others.
Likewise, MSP will not authorize items in the labelling which are not strictly concordant with the information submitted by the manufacturer or importer to the MSP.
17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?
Law 15,703 and Decrees 521/984 and 18/989 only allow the marketing of medicines and medical devices to the public through authorized pharmacies.
For its part, as regards advertising:
- it is only allowed regarding products duly registered with the MSP (reference to drugs which have not been registered, even if indirectly, is not allowed);
- over-the-counter drugs are the only category in which direct advertising to the public may be made through different means and;
- all material and information which refers to drugs belonging to a different category (e.g. prescription drugs) must only be directed to healthcare professionals (physicians, chemical-pharmaceuticals, etc.).
Regarding advertising of biologicals, which is limited to healthcare professionals, article 23 of Decree 38/2015 states that “when registering or renewing a biotechnological drug, all advertising and promotion projects directed to health professionals must be submitted to the health authority. (…)”.
All information material in relation to medical devices which must be handled by healthcare professionals or for which patients need the involvement of a healthcare professional (e.g. tomographs, vaporizers, etc.) must be exclusively directed to these and/or to regulated sales channels (e.g. healthcare institutions, clinics). This is the interpretation of the MSP since there is no express law regulating this matter.
18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?
Medicines and devices can be sold to the public only through authorized pharmacies. Medicines and devices cannot be sold via post. The only exception for selling drugs via post is under the “compassionate use” proceeding (regulated under Resolution No. 692/013). The mechanism consists of allowing the patient to import products that still do not have a market authorization in Uruguay or that are in the process of clinical development, upon a specific prescription from the treating physician.
19. What are the restrictions and requirements for electronic marketing and advertising via email, by the Internet, social media, and other channels?
Over-the-counter drugs are the only category of drugs which may be the object of direct advertising addressed to the public through different means. There are no limitations as regards the places where to advertise but all advertising must meet the following criteria:
- it must refer to products duly registered in Uruguay;
- it must be strictly concordant with the information submitted by the manufacturer or importer to the health authority;
- it must contain information which is clear and true and adhere to the accuracy, impartiality and objectivity of the information;
- it may not contain ambiguous information which might be misleading for the consumer as regards its use and be therefore detrimental to health;
- if reference is made to the treatment of symptoms or illnesses, the advertising must include the suggestion to seek medical advice (in dimensions that will depend on the context of each advertising);
- in the event there might exist harmful effects to health due to misuse, for example, the advertising must include a warning to seek medical control.
20. May medicines and devices be advertised or sold directly to consumers?
Please refer to Question 17 abovementioned.
21. How is compliance monitored?
Please refer to Question 8 in Regulatory, Pricing, and Reimbursement Overview.
22. What are the potential penalties for noncompliance?
Please refer to Question 9 in Regulatory, Pricing, and Reimbursement Overview.