Source: https://biologicspolicy.com/country/argentina
Timestamp: 2019-09-19 00:08:49
Document Index: 252120134

Matched Legal Cases: ['§ 3', '§ 4', '§ 3', '§ 4', '§ 8', '§ 2', '§ 4', '§ 4', '§ 4', '§ 2', '§ 6', '§ 8', '§ 4', '§ 3', '§ 5', '§ 6', '§ 5', '§ 5', '§ 6', '§ 6', '§ 8', '§6', '§ 2', '§ 4', '§ 9', '§ 4', '§ 4']

In Argentina, the regulatory body for approval of medicines, including the scientific evaluation of biologics and biosimilars is the Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (National Administration of Drugs, Foods and Medical Devices; ANMAT). ANMAT comes under the authority of the Ministry of Health.
In Argentina, biosimilars are known as Medicamento biológico similar (similar biological medicines)
Argentina is Partially Compliant.
The WHO guidance was compared to the relevant sections across the ANMAT guidelines resulting in an overall score for Argentina of 2.57/5. This means the ANMAT guidelines are partially or fully compliant with WHO in some areas, but in more than half of the policy components, they are minimally or non-compliant with WHO standards.
There are fifteen areas where ANMAT is not as specific as WHO, being either non-compliant, minimally compliant, or partially compliant with the WHO biosimilar policy.
When comparing the biosimilar to the original medicine, the ANMAT guidelines do not specify that the same host cell should be used to produce the medicine.
The guidelines do not specify the intent of this analysis is to identify significant functional differences between the biologic and biosimilar.
The ANMAT does not require head to head studies to evaluate the stability of the biosimilar as compared with the original biologic
The guidelines do not address in vitro studies and in vivo study description does not provide the level of specificity and detail provided by the WHO.
This topic is not addressed by the ANMAT guidelines.
Clinical, Pharmacokinetics and Pharmacodynamics:
In Argentina, biosimilar guidelines were issued in 2008 by ANMAT.[1] The guidelines follow the principles of the EU biosimilars guidance.
Guideline on Biological Medicinal Products
First issued July 2008; Most recent update July 2008
[§ 3 in 2a] Biological products containing well-characterized proteins.
[§ 4 in 2a] Excludes products using clearly different manufacturing processes from that of the Reference Product (e.g., use of transgenic organisms vs. cell cultures).
[Annex 1, ch. III in 2b] Excludes: (1) vaccines regulated by Regulation 705/05; (2) products not requiring registration in the Registry of Medicinal Products; (3) individualized allergenic vaccines; and (4) human whole blood, plasma, and blood cells, and their components.
[§ 3 in 2a] The comparability exercise must be designed to demonstrate that the biosimilar has quality attributes highly similar to those of the reference product.
[§ 4 in 2a] Through characterization and analysis, the biosimilar must be shown to have similar behavior to the Reference Product in terms of quality, safety, and efficacy.
[§ 8 in 2a] If significant differences are observed between the proposed product and the Reference Product after evaluating the quality, nonclinical, and clinical data, licensing of the proposed product (as a biosimilar) may be denied.
[§ 2 in 2a] Comparisons between the biosimilar and the reference product should always use the same reference product.
[§ 4 in 2a] The reference product must: (1) be licensed by the regulatory authority (ANMAT) and marketed in Argentina; or (2) be licensed by another health authority with regulatory functions, principles, and PV activities in line with those of Argentina, have sufficient experience and knowledge regarding its use in the market available, and have information on its specifications and characteristics available.
The reference product must be licensed based on the evaluation of a full dossier, including quality, nonclinical, and clinical information.
[Annex I, ch. III in 2b] Information related to product formulation and its components must be available for verification. Qualitative and quantitative composition, as well as the function of each substance in the formulation, must be specified.
Specifications and limits for excipients must be provided if they are not in official pharmacopoeias. A full description of the analytical method must be submitted for excipients that are not in official pharmacopoeias and are used for the first time in a medicinal product.
[§ 4 in 2a] Same as that of the reference product.
[§ 4 in 2a] Dosage form and “concentration” must be the same as that of the reference product.
[§ 2 in 2a] The applicant must submit data from trials demonstrating “similar behavior” between the biosimilar and reference product in terms of identity, potency, purity, safety, and efficacy. Comparisons between the biosimilar and the Reference Product should be head-to-head comparisons.
[§ 6 in 2a] The comparability exercise must be accompanied by clinical (and nonclinical) studies. The requirements for these studies will be determined by: (1) the nature of the active substance and its structural complexity; (2) information on the in vivo behavior of the active pharmaceutical ingredient and/or product; (3) impurities; (4) information on the post-market behavior of “similar products”; and (5) the relationship between adverse reactions and molecular characteristics.
[§ 8 in 2a] The ANMAT may require additional clinical data if significant differences are observed during the comparability exercise.
[§ 4 in 2a] If the reference product’s active ingredient is obtained through isolation, the applicant must submit studies demonstrating that the active ingredient has not suffered changes during the isolation process. The applicant must use a battery of state-of-the-art tests to determine the structure, function, purity, and heterogeneity of the active ingredient.
[§ 3 in 2a] Adequate physicochemical and biological trials must enable the detailed characterization of the biosimilar.
[§ 5 in 2a] The applicant must use appropriate techniques to determine the biosimilar’s physicochemical products.
The comparability exercise should take into account the complexity of the molecular entity. Depending on the molecule’s physicochemical properties (e.g., primary, secondary, tertiary, and quaternary structure, with or without post-translational modifications, or degree of glycosylation and N/C terminal modifications), an extended battery of tests may be required.
[§ 6 in 2a] The nature of the active substance and its structural complexity are factors in determining the requirements for clinical and nonclinical studies.
[§ 5 in 2a] The applicant must use appropriate techniques to determine “biological and immunochemical” activity (if applicable).
[§ 5 in 2a] The applicant must use appropriate techniques to identify impurities.
[§ 6 in 2a] The comparison of the reference product’s and biosimilar’s impurity profiles is a factor in determining the requirements for clinical and nonclinical studies.
[Annex I, ch. III in 2b] An applicant must submit information about starting materials, including quality specifications and the detection of adventitious agents. When using animal and/or human origin components, the applicant must submit evidence of the absence of foreign agents or of the ability to eliminate or reduce these agents during the manufacturing process.
Testing results must be submitted for a minimum of three batches.
[Annex I, ch. III in 2b] Stability studies involving the proposed storage and packaging conditions must be submitted.
[Annex I, ch. III in 2b] For the finished product, if the quality specification is from the Argentine Pharmacopoeia or another internationally recognized pharmacopoeia, the application must indicate the specifications and limits applied, along with the acceptance/rejection criteria.
If the specification is determined by the manufacturer, the applicant must submit: (1) information about the physicochemical, biochemical, and immunological characterization of the biosimilar; (2) information about the biosimilar’s purity and impurity profiles; (3) a full description of analytical methods used, their limits, and acceptance/rejection criteria; and (4) reference standards or materials used and information about their validation.
[§ 6 in 2a] The comparability exercise must be accompanied by nonclinical (and clinical) studies. The requirements for these studies will be determined by: (1) the nature of the active substance and its structural complexity; (2) information on the in vivo behavior of the active pharmaceutical ingredient and/or product, (3) impurities; (4) information on the post-market behavior of “similar products”; and (5) the relationship between adverse reactions and molecular characteristics.
[§ 8 in 2a] The ANMAT may require additional nonclinical data if significant differences are observed during the comparability exercise.
[§6 in 2a] In vivo studies: Requirements for nonclinical (and clinical) studies will be determined by, among other factors, information on the in vivo behavior of the active ingredient and/or product.
[§ 2 in 2a] The applicant must submit evidence demonstrating “similar behavior” in terms of safety and efficacy. Comparisons between the biosimilar and the Reference Product should be head-to-head comparisons.
[§ 4 in 2a] The indications of the biosimilar must be the same as those for which the Reference Product was approved. Scientific data supporting each indication must be available.
[§ 9 in 2a] The applicant must assure that by the time of licensing there will be in place an appropriate post-market surveillance system. It should include a qualified professional in charge of supervising the system and adequate provisions for providing notice of adverse reactions occurring in Argentina and abroad.
[§ 4 in 2a] A biosimilar is well-characterized through the use of an established battery of modern analytical methods.
[§ 4 in 2a] The applicant must use a battery of state-of-the-art tests to determine structure, function, purity, and heterogeneity of the active ingredient.
[1] Source: http://gabionline.net/Biosimilars/Research/Regulation-of-similar-biotherapeutic-products-in-Latin-America