Sanitary Registration of Medicines and Biological Products in Colombia

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[1]. These are:

1. Chemically synthesized drugs: decree 846 of 2016[2].
2. Biological drugs: decree 1782 of 2014[3].
3. Homeopathic medicines: decree 3554 of 2004[4] and decree 1861 of 2006[5].
4. Phytotherapeutic drugs: decree 2266 of 2004[6] and decree 3553 of 2004[7].

*The regulation of vital medicines not available in the country is governed by Decree 481 of 2004[8]. 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[9].

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:

1. Route of administration.
2. Dosage and frequency of administration.
3. Pharmacological indications and therapeutic use.
4. 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°).