By: Laura Fuentes Zaldaña

Head of Life Sciences – LatinAlliance El Salvador

When registering a Pharmaceutical Specialty (Pharmaceutical Product), it is important to keep in mind the requirements adopted and agreed by the countries of the Central American region, and which are required by the National Directorate of Medicines in El Salvador, which is the regulatory entity.

On this occasion we will see critical points evaluated in some Central American Technical Regulations:

  • Quality Verification – RTCA 11.03.47:07
  • Stability Studies – RTCA 11.01.04:10
  • Labeling of Pharmaceutical Products – 11.01.02:04

QUALITY VERIFICATION: establishes the analytical tests that must be carried out to verify the quality of pharmaceutical products.

The tests are classified depending on the pharmaceutical form:

  • Coated or uncoated tablets
  • Hard or soft gelatin capsules
  • Solutions and Emulsions (Oral and Topical)
  • Suspensions (Oral and Topical)
  • Solutions, Emulsions and Suspensions (Injectable, Ophthalmic and Otic Sterile)
  • Powders and Granules (Oral and Topical)
  • Powders and Granules (Oral and Topical) to Reconstitute
  • Powders to Reconstitute (Injectables)
  • Creams, Ointments, Pastes and Gels (Topical)
  • Creams, Ointments and Gels (Ophthalmic)
  • Suppositories (Rectal, Urethral and Vaginal) and Vaginal Suppositories Tablets or Capsules
  • Aerosols, Atomizers and Inhalers
  • Transdermal Systems and Plasters or Adhesive Tapes
  • implants

It is important to keep the following in mind:

  1. The number of samples required for sampling and analysis depends on the dosage form of the product.
  2. Samples may be required for the Registration, Post-registration and Pharmacovigilance of pharmaceutical products.

STABILITY STUDIES: establishes the guidelines for carrying out stability studies in order to determine the validity period of medicines.

Stability Studies are tests that are carried out to obtain information on the conditions in which raw materials, semi-finished products or finished products must be processed and stored, as the case may be. Stability tests are also used to determine the shelf-life of the drug in its original primary packaging and under specified storage conditions. Stability studies can be: Long-term or Accelerated studies, and must be carried out in 3 pilot batches or 3 production batches.

When we talk about validity period, what do we mean?

It is the date that indicates the end of the period of effectiveness of the active principles of the product (date labeled on the packaging) and after which they should not be administered; since it has been based on the stability studies of the drug.

What are the types of Stability Studies?

Long-term: also known as Real Time, are those in which the physical, chemical, biological or microbiological characteristics of the drug are evaluated during the expiration period, under controlled storage conditions.

In El Salvador, the conditions that apply for this type of study according to the World Health Organization are: Temperature and Relative Humidity of 30º C ± 2º C and 75% ± 5% respectively (Climatic Zone IV b), as follows:

PeriodAnalysis Frequency
First yearInitial time, intermediate time and 12 months.
Second year24 months
Third yearEvery 12 months up to a maximum of 5 years.

For products that require special storage conditions, the conditions are:

Storage conditionsMinimum PeriodAnalysis Frequency
Refrigeration5 ° C ± 3 ° CTime not less than 12 monthsInitial time, intermediate time and 12 months
Freezing-20°C ± 5°CTime not less than 12 monthsInitial time, intermediate time and 12 months

Accelerated: these studies are designed in order to increase the rate of chemical or physical degradation of a drug, for which extreme storage conditions are used. The purpose of these studies is to determine the kinetic parameters of the degradation processes or to predict the shelf-life of the drug, under normal storage conditions. The design of these studies may include elevated temperatures, high humidities, and exposure to intense light.

The results of the accelerated stability studies must be complemented by the studies carried out under normal storage conditions or under defined storage conditions.

The conditions for carrying out this type of study are:

Storage conditionsAnalysis Frequency
40 °C ± 2 °C at 75% ± 5% RH for solid dosage formsInitial, 90 days and 180 days
40 °C ± 2 °C for liquid and semi-solid dosage formsInitial, 90 days and 180 days

In the case of special drugs, what was verified in the stability study is:

Storage conditionsMinimum PeriodAnalysis Frequency
Refrigeration25 °C ± 2 °C at 60% ± 5% RHTime not less than 6 monthsInitial, 3 and 6 months

There are some changes after the registration of a medicine where it is required to demonstrate with stability studies that the product maintains its quality, where we can mention: Change in the primary packaging material, changes in the qualitative-quantitative formula (>10% of the total of the formula), manufacturing method and site, among others.

The RTCA establishes the parameters to be evaluated according to the pharmaceutical form of the drug, as well as the information that the stability study results form must include.

LABELING OF PHARMACEUTICAL PRODUCTS FOR HUMAN USE: This document establishes the minimum requirements that the labeling of pharmaceutical products must meet, both for products from Central America and abroad.

It is important to understand the types of packaging that exist for medicines, since for each of them the RTCA details the type and amount of information that must be included for consumer reading:

Primary packaging: it is the container or container inside which the medication is directly placed in the finished pharmaceutical form; It is the one that is in direct contact with the product.

Secondary packaging: it is the container inside which the primary packaging containing the drug is placed in its finished pharmaceutical form for its distribution and commercialization.

Special conditions for labeling:

  • It should not disappear under normal handling conditions.
  • It must be readable with the naked eye.
  • Written in Spanish language; It is permissible to place the information in other languages, but it must be essentially the same.
  • It can be made of paper or any other material that can be adhered to the packages, or permanently printed on them.
  • The printing of the labels that adhere to the packaging must be on the back of the same, as long as they are clearly visible and legible through the container or packaging with its content.
  • If the product is going to be marketed without the secondary packaging, the labeling of the primary packaging must comply with all the requirements indicated for the secondary container or packaging.

The RTCA establishes the classification of the requirements and demands depending on the type of pharmaceutical form, as follows:

  • Tablets (dragees and tablets), capsules, troches, suppositories, ovules, transdermal patches and other similar forms (any route of administration).
  • Solutions, syrups, elixirs, suspensions, emulsions, lotions, powders for the preparation of suspensions or solutions, injectables in ampoule, pre-filled syringes, vials or large-volume parenterals, aerosols and other similar forms (any route of administration).
  • Ointments, ointments, creams, gels, jellies, pastes and other similar forms (any route of administration).

In common, within the information that they must carry and is mandatory, we can mention: Name of the medication, Lot number, Expiration date, Content in units, Pharmaceutical form, Route of administration, Product composition per dose unit, Registration Sanitary, Name of the owner, Name of the Manufacturer, Free Sale (if applicable), among others.

There are also special mandatory legends that must be placed on the label for products containing the following substances: Tartrazine (oral use), Benzyl Alcohol (parenteral use), Tetracyclines, Acetylsalicylic Acid, Acetaminophen (Paracetamol), Aspartame (oral use) , Opium, Loperamide or Diphenoxylate (indicated in diarrhea), Narcotic or Psychotropic.

In addition, it is essential to include information such as Indications, Warnings, Contraindications, Interactions, Dosage, etc., for which it is allowed to use the insert, instructions or leaflet in cases where it cannot be placed in the primary or secondary packaging due to its extension.

For detailed information on each document, you can contact our team of professionals at LatinAlliance at +503 2263 6366 or contact the author of this article, Laura Fuentes lfuentes@latinalliance.co