The regime of sanitary registrations for drugs and biological products is partially regulated in Decree 677 of 1995. This could be considered as a general regime because, depending on the type of drug, there are special regulations that are found in subsequent regulations.
What is meant by drugs and biological products?
Decree 677 of 1995 defines drugs as follows:
That pharmaceutical preparation obtained from active ingredients, with or without auxiliary substances, presented in pharmaceutical form and used for the prevention, relief, diagnosis, treatment, cure or rehabilitation of disease. Containers, labels, tags and packaging are an integral part of the drug, since they guarantee its quality, stability and proper use.
On the other hand, Decree 1782 of 2014 defines biological products or drugs as:
Drugs derived from living organisms or cells or their parts. They can be obtained from sources such as tissues or cells, components of human or animal blood (such as antitoxins and other antibodies, cytokines, growth factors, hormones and clotting factors), viruses, microorganisms and products derived from them such as toxins. These products are obtained by methods comprising, but not limited to, cell culture of human or animal origin, culture and propagation of microorganisms and viruses, processing from human or animal biological tissues or fluids, transgenesis, recombinant Deoxyribonucleic Acid (DNA) techniques, and hybridoma techniques. The drugs resulting from these last three methods are called biotechnological.
How are drugs and biological products classified?
The categories into which these products have been divided in order to implement an additional and complementary special regulation to Decree 677 of 1995 can be found on INVIMA’s website. These are:
- Chemically synthesized drugs: decree 846 of 2016.
- Biological drugs: decree 1782 of 2014.
- Homeopathic medicines: decree 3554 of 2004 and decree 1861 of 2006.
- Phytotherapeutic drugs: decree 2266 of 2004 and decree 3553 of 2004.
*The regulation of vital medicines not available in the country is governed by Decree 481 of 2004. These are exempt from sanitary registration for their production, importation and commercialization, however, they must comply with other specific requirements regulated in the aforementioned regulations.
Which drugs and biological products require sanitary registration?
Article 1° of Decree 2510 of 2003 modified article 13° of Decree 677 of 1995, which states which types of drugs do require sanitary registration, as follows:
Medicines, including pharmaceutical preparations based on natural resources, require for their production, importation, processing, container, packaging, dispensing and commercialization a sanitary registration, issued by INVIMA or whoever takes its place or by the delegated sanitary authority, prior compliance with the technical, scientific, sanitary and quality requirements set forth in this decree.
It then indicates which drugs do not require sanitary registration and that, on the contrary, INVIMA will issue an export certificate to the interested party. Thus:
Medicines, including pharmaceutical preparations based on natural resources, finished, semi-finished or in bulk, manufactured in Colombia exclusively for export, by laboratories that comply with Good Manufacturing Practices in force, shall not require sanitary registration, unless the interested party requests it under the manufacture and export modality or the importing country so requires.
This export certificate shall be valid for one (1) year.
What are the general requirements to apply for INVIMA’s sanitary registration for drugs and biological products?
Before describing the general requirements for this type of procedure, it is pertinent to remind the reader that in order to apply for each particular drug, the special regulations for each category should be consulted. Likewise, the legal and technical requirements for each type of medicine (homeopathic, chemical, biological, phytotherapeutic, etc.) may also be consulted on the INVIMA website.
Article 9 of Decree 677 of 1995 establishes a distinction between two types of sanitary registrations: a) Those included in the officially accepted pharmacological standards, and b) New drugs as defined in Article 2 of this Decree.
Requirements for drugs included in the pharmacological standards:
a) Pharmaceutical evaluation: the purpose of the pharmaceutical evaluation is to assess the technical capacity of the manufacturer of the manufacturing process and the quality of the product (Art. 21°).
Documentation for pharmaceutical evaluation (Art.22°)
To request the pharmaceutical evaluation of a drug, the interested party must fill out the application form duly signed, as well as for locally manufactured products endorsed by the Pharmaceutical Chemist Technical Director of the Laboratory or Manufacturing Industry, accompanying the following information and documentation to INVIMA:
a) Copy of the operating license in force and of the report of the visit to the manufacturing establishment, by which compliance with good manufacturing practices was verified, or copy of the last report of the visit, if it is within the term established in article 12 of this Decree;
b) Pharmaceutical form and commercial presentation;
c) The composition or quantitative formula of the product, identifying with generic and chemical name, all the substances that are part of it according to the nomenclature “International Union of Pure and Applied Chemistry, IUPAC”, as follows:
- Per unit, in dosage forms, in case of tablets, dragees, capsules, ovules, suppositories, injectables and similar.
- Per 100 milliliters, in non-injectable liquid compositions.
- Per milliliter, in liquids for drop administration and multidose injectables. Per 100 grams, in powders, ointments, creams and similar.
- Per gram of powder to reconstitute to 100 milliliters.
- In percentage by weight or volume, indicating separately the active substances, solvents and propellant gases, in the case of aerosols.
The corresponding formula must be presented in two parts, as follows:
Active ingredients: Excipients: stabilizers, colorants, vehicles and other compounds in general;
d) Structural and condensed formula of the active principles, when applicable;
e) Standardized manufacturing batch formula;
f) Detailed description of the manufacturing process;
g) Certification of the reference standards used for quality control of the active ingredients, when applicable;
h) Quality specifications and results of quality controls on raw materials (active ingredients and formulation auxiliaries) and other inputs in the production process;
i) Quality specifications and description of the controls carried out on the product during the manufacturing process. Presentation of the results of such controls;
j) Quality specifications and results of quality controls for the finished product.
k) Methodology of analysis of the finished product. When it corresponds to one of the pharmacopoeias accepted in the country, the manufacturer shall indicate the name of the pharmacopoeia, its edition and the corresponding page of the same. If the methodology of the finished product does not correspond to any of the official pharmacopoeias, the manufacturer must submit the documents proving the complete validation analyses. For solid dosage forms, whose active ingredient is official in several pharmacopoeias, and if the chosen pharmacopoeia does not have the dissolution test, compliance with the dissolution test required in the United States Pharmacopoeia, USP, will be required. When INVIMA considers it convenient, it may establish products for which it requires an analysis methodology contained in one of the accepted pharmacopoeias;
l) Scale sketch of the label project and projects of the containers and packaging of the medicine, in accordance with the provisions of this Decree;
m) Summary of pharmacological information including:
- Route of administration.
- Dosage and frequency of administration.
- Pharmacological indications and therapeutic use.
- Contraindications, side effects and warnings
n) Product stability and shelf life studies;
ñ) Results of the bioavailability and bioequivalence studies for the products defined by INVIMA, prior concept of the Review Commission of Pharmaceutical Products, and in accordance with the parameters established by INVIMA.
b) Legal evaluation.
The legal evaluation includes the legal study of the documentation submitted by the interested party for the granting of the registration and its conformity with the legal norms that regulate such matters (Art.24°).
Documentation for the legal evaluation (Art.24°)
a) Name of the product for which registration is requested and modality;
b) Name or company name of the natural or legal person in whose name the registration is requested;
c) Name of the pharmaceutical laboratory or manufacturing industry, or copy(s) of the manufacturing contract(s) when the product is manufactured by third parties. The contract must indicate the products to be manufactured, the manufacturing steps to be performed and whether quality control will be carried out;
d) The contract manufacturer must strictly comply with the good manufacturing practices approved by the Ministry of Health, and have a valid sanitary operating license, without prejudice to the provisions of Article 12 of this Decree;
e) Copy of the certification of the pharmaceutical evaluation issued by an accredited entity;
f) Proof of incorporation, existence and legal representation of the petitioning entity;
g) Power of attorney to manage the procedure, conferred to a lawyer, if applicable;
h) Certificate issued by the Superintendence of Industry and Commerce, in which it is stated that the trademark is registered in the name of the interested party or that he has applied for its registration, which is in process. When the owner of the trademark is a third party, the authorization for the use of the trademark must be attached;
i) Receipt for product analysis rights;
j) Receipt for sanitary registration and publication fees.
Requirements for new drugs:
Article 26. For the purpose of issuing the sanitary registration for new drugs, the following will be required:
a) Pharmacological evaluation;
b) Pharmaceutical evaluation;
c) Legal evaluation.
It comprises the procedure by which the health authority forms a judgment on the usefulness, convenience and safety of a drug (Art.27°).
Documentation for pharmacological evaluation (Art.27°)
The evaluation will be carried out taking into account the following product characteristics:
- Indications, contraindications, interactions, and warnings Benefit-risk ratio
- Toxicity Pharmacokinetics
- Marketing conditions
- Special restrictions.
Paragraph 1. When the product for which registration is requested is registered in at least two (2) reference countries and has not been rejected in any other reference country, a summary of the clinical information with the corresponding bibliography, in a format defined by INVIMA, will be required for the pharmacological evaluation. The Pharmaceutical Products Review Commission may request additional information about the product, when there are doubts about the product.
Paragraph 2. For the purposes of this article, the reference countries are: United States of America, Canada, Germany, Switzerland, France, England, Denmark, Holland, Sweden, Japan and Norway.
As regards pharmaceutical and legal evaluation, they are governed by the rules applicable to the products included in the pharmacological standards.
Article 30. In the case of sanitary registrations for importing and selling, importing, packaging and selling, and importing, semi-manufacturing and selling medicines, the following requirements must be complied with:
a) For the importation of medicines included in the pharmacological standards:
– Technical evaluation by INVIMA.
– Legal evaluation
“The interested party shall file the application with INVIMA, to which shall attach for technical evaluation purposes, the documents contained in letters b, c, d, e, f, k, m, n, and ñ of Article 22 of this Decree, as well as the quality specifications of the raw materials, of the product in process and finished product, a summary of the manufacturing process as well as a copy of the labels of containers and packaging. For the purposes of the legal evaluation, those indicated in letters a, b, e, f, g, h, i and j) of article 24 must be attached”.
b) For the importation of medicines not included in the pharmacological standards:
– Pharmacological evaluation
– Technical evaluation by INVIMA
– Legal evaluation.
In addition to the documents mentioned in the previous paragraph, the following will also be required:
a) Quality certificate for products subject to international trade, issued by the sanitary authority of the exporter’s country of origin, which shall contain at least the following information:
– Certification that the product has been authorized for use in the territory of the exporting country and which shall indicate:
- Active ingredient, pharmaceutical form and concentration, registration holder.
- Registration number and expiration date when applicable.
– Certification that industrial facilities and manufacturing operations conform to nationally accepted good manufacturing practices.
– Certification that the facilities where the product is manufactured are subject to periodic inspections by the competent health authorities;
b) Express authorization from the manufacturer to the importer to apply for sanitary registration in its name, use the trademark and/or market the product, as the case may be.
Paragraph 1. In the case of the importation of medicines not included in pharmacological standards, the interested party must request, in the first instance, the pharmacological evaluation before the INVIMA, following the procedure set forth in Articles 27 and 28 of this Decree.
Paragraph 2. Documents issued abroad must be accredited in accordance with the provisions of the regulations in force on the matter and, especially, the provisions of the Code of Civil Procedure. Additionally, documents that are not in Spanish will require an official translation. The date of issuance of these documents shall not be more than one (1) year prior to the date of the application for registration.
Paragraph 3. Sanitary registration will not be granted to products manufactured in countries where their production and trade are not regulated and controlled.
Paragraph 4. Imported products must comply with the same quality requirements demanded to products of national manufacture. Stability results performed by the manufacturer under extreme weather conditions, as specified in international standards, will be accepted. Products imported in bulk without primary packaging shall be subjected to local stability tests.
When deemed necessary, INVIMA may request stability studies performed locally on imported products once they enter the country.
What does the sanitary registration process consist of?
It is important to note that this procedure can be carried out by submitting the documents in person at the INVIMA offices or virtually. on the INVIMA website. This procedure does not require an attorney.
Procedure for drugs contained in pharmacological standards: (Art.25°)
The interested party shall request INVIMA to carry out the pharmaceutical evaluation under the terms and conditions set forth in Articles 22 and 23 of this Decree.
With the technical documentation referred to in Article 22 above, the result of the pharmaceutical evaluation, the legal documentation referred to in the previous article, and the duly completed application, the interested party shall apply for the sanitary registration before INVIMA.
If the documentation is incomplete at the time of receipt, the application will be rejected outright, in accordance with the provisions of the Contentious Administrative Code.
Once the application with its respective supports is received, INVIMA will proceed to carry out the legal evaluation, process the results of the two evaluations and grant or deny the sanitary registration or communicate that it is necessary to complement or add the information, for which the competent official will have a peremptory term of twenty (20) working days.
5. If additional information or clarification of the documents submitted is needed, the interested party will be required only once to provide the missing information, for which the applicant will have a term of sixty (60) working days. If within this period the interested party does not provide the requested information, it will be understood that the petition has been withdrawn and, consequently, INVIMA will proceed to declare the petition abandoned and return the file to the interested party by certified mail to the last address on file.
Once the petitioner submits the requested information, INVIMA will have a term of ten (10) working days to deny or approve the requested registration.
Procedure for new drugs: (Art.29°)
- The interested party shall request before INVIMA the performance of the pharmacological evaluation, under the terms and conditions set forth in Articles 27 and 28 of this Decree.
- The interested party must also request INVIMA or any of the accredited entities to carry out the pharmaceutical evaluation under the terms and conditions set forth in Articles 22 and 23 of this Decree.
- With the result of the pharmacological and pharmaceutical evaluations, the legal documentation referred to in Article 24 of this Decree and the application duly filled out, together with all the supports that served as the basis for the different pharmaceutical and pharmacological evaluations, the interested party will proceed to apply to INVIMA for the sanitary registration.
- If the information is incomplete at the time of receipt of the documents, the request will be rejected in accordance with the provisions of the Contentious Administrative Code.
- Once INVIMA receives the application with its respective supports, it will proceed to carry out the legal evaluation. It will then process the results of the three evaluations and issue or deny the registration or communicate that the information must be complemented, for which the competent official will have a peremptory term of ten (10) working days.
- If additional information or clarification of the documents submitted is needed, the interested party will be required only once to provide the missing information, for which the applicant will have a term of sixty (60) working days. If within this period the interested party does not provide the requested information, it will be understood that the petition has been withdrawn and, consequently, INVIMA will proceed to declare the petition abandoned and return the file to the interested party by certified mail.
- Once the petitioner submits the missing information, INVIMA will have a term of ten (10) working days to issue the administrative act approving or denying the requested registration.
Procedure for imported products: (Art.31°)
- The interested party must file the application with INVIMA, attaching the documents previously indicated, depending on whether it is a new drug or a drug included in the pharmacological standards.
- If the information is incomplete at the time of receipt, the request shall be rejected, in accordance with the provisions of the Contentious Administrative Code.
- In the event that it is necessary to add or clarify the information provided, the interested party will be required only once to provide the missing information, for which the applicant will have a term of forty (40) working days from the date of communication of the requirement. If within this period the interested party does not provide the requested information, it will be understood that the petition has been withdrawn and consequently INVIMA will proceed to declare the petition abandoned and return the file by certified mail.
- Once the petitioner submits the aforementioned information, INVIMA will have a term of ten (10) working days to deny or approve the requested registration.
What are the costs for the processing and renewal of the medical device sanitary registration?
Resolution 2019058384 of December 27, 2019. updates the rates managed by INVIMA for all types of procedures, including the sanitary registration of medicines and biological products in terms of Tax Value Unit (UVT) where each unit has a value of 35,607 pesos for the year 2020.
What is the validity of the sanitary registration?
According to article 5 of Decree 2086, which modified article 16 of Decree 677 of 1995, the sanitary registrations of medicines and their renewals will be valid for five (5) years and will be issued by INVIMA or the delegated authority through an administrative act.
How is the renewal of the sanitary registration processed?
Article 17 of Decree 677 of 1995 states that renewals of sanitary registrations will be carried out following the same procedure of their issuance with regard to pharmaceutical or technical and legal evaluations. In addition, for renewal, quality control analysis and evaluation of the manufacturing process and compliance with good manufacturing practices or current technical manufacturing standards may be performed.
The pharmaceutical or technical evaluation must be requested before INVIMA within the year prior to the expiration of the registration. The application for renewal must be filed with INVIMA at least three (3) months prior to the expiration of the sanitary registration. Any application for renewal of a sanitary registration that is not submitted within the term provided herein shall be processed as a new application for sanitary registration.
Paragraph 1. In the case of the requirement to submit production records, which is required for the pharmaceutical or technical evaluation, it shall be understood that these are those corresponding to the last three (3) industrial batches produced.
Paragraph 2. If the sanitary registration has expired without the renewal application being filed, the application is abandoned or abandoned or the application has not been filed within the term provided herein, the corresponding product may not be imported into the country or manufactured, as the case may be. If there are stocks on the market, INVIMA will give the interested parties a period of time to dispose of them, which may not exceed six (6) months. If after the term has elapsed there are products on the market, INVIMA will order their seizure in accordance with the provisions of this Decree.
Is a certificate of compliance with good manufacturing practices required?
Yes. Article 6 of Decree 677 of 1995 establishes that all drug manufacturing establishments must apply to INVIMA, directly or through their legal representative in Colombia, for a Certificate of Compliance with Good Manufacturing Practices. Decree 549 of 2001 regulates the procedure and requirements for its application.
Article 1 of Decree 162 of 2004 modified Article 3 of Decree 549 of 2001 regarding the Certificate of Good Manufacturing Practices for imported drugs, stating the following:
In the case of imported drugs, the certificate of compliance with Good Manufacturing Practices, GMP or its equivalent will be accepted as long as it specifies the manufacturing areas, production processes and/or type of product or products, granted by the competent authority to the interested parties, with respect to the manufacturing laboratories located in the following countries: United States of America, Canada, Germany, Switzerland, France, United Kingdom, Denmark, Holland, Sweden, Japan and Norway, or by those who have signed mutual recognition agreements with these countries.
Likewise, the Instituto Nacional de Vigilancia de Medicamentos y Alimentos, INVIMA, will accept:
a) Certificates of compliance with Good Manufacturing Practices or their equivalent, granted by the United States Food and Drug Administration (FDA) or its equivalent, to laboratories located outside the territory of the United States of America;
b) Certificates of compliance with Good Manufacturing Practices or their equivalent, granted by the World Health Organization, WHO, or the Pan American Health Organization, PAHO;
c) Certificates of Compliance with Good Manufacturing Practices or its equivalent, granted by the health authority of the European Union, European Agency for the Evaluation of Medicinal Products, EMEA, whoever acts in its stead;
d) Certificates of Compliance with Good Manufacturing Practices or their equivalent, granted by the health authorities of countries with which the European Agency for the Evaluation of Medicinal Products, EMEA, or whoever is acting on its behalf, has signed mutual recognition agreements.
e) The certificates of Good Manufacturing Practices Compliance or its equivalent, granted by the European Agency for Evaluation of Medicinal Products, EMEA, or whoever takes its place, to manufacturers located outside the territory of the European Union”.
Our lawyers are experts in the process of sanitary registration of drugs and biological products before the INVIMA and can provide you with the help and advice you require, if you want to know more about our services you can contact us through our website.
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