CBPE

Promoting science based, medically appropriate policies for biologic medicines

Mexico
Number of Biosimilars Available

1

Country Spotlight: Mexico

The Federal Commission for the Protection against Sanitary Risks (COFEPRIS- Comisión Federal para la Protección contra Riesgos Sanitarios) is the regulatory body for approval of medicines in Mexico, including the scientific evaluation of biologics and biosimilars. COFEPRIS comes under the authority of the Department of Health.

In Mexico, biosimilars are known as biocomparables.

Biosimilars Available

As of April 2016, there is 1 biosimilar approved for use in Mexico

  • A medicine used to treat Rheumatoid Arthritis, Non-Hodgkin’s Lymphoma, and Leukemia (Rituximab)

Score Overview

Mexico is Partially Compliant.

The WHO guidance was compared to the relevant sections across the COFEPRIS guidelines resulting in an overall score for Mexico of 2.3/5. This means the COFEPRIS 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.

The graph below shows individual scores by each of the 28 components of biosimilar policy

There are seventeen areas where COFEPRIS is not as specific as WHO, being either non-compliant, minimally compliant, or partially compliant with the WHO biosimilar policy.

Scores by measured component
Gaps
Gap 1

Scope:

The guidelines are non-specific and vague regarding what is in scope.

Gap 2

Reference Product:

When comparing the biosimilar to the original medicine, the COFEPRIS guidelines do not specify that the same host cell should be used to produce the medicine.

Gap 3

Formulation:

This topic is not addressed by the COFEPRIS guidelines.

Gap 4

Route of Administration:

The guidelines do not state that the route of administration for the biosimilar should be the same as for the original biologic.

Gap 5

Quality/analytical, General Considerations:

The guidelines do not address that an investigation of differences between the biosimilar and the original biologic should take into account lot-to-lot differences in commercial lots of the original biologic.

Gap 6

Quality/analytical, Isolation of Drug Substance:

This topic is not addressed by the COFEPRIS guidelines.

Gap 7

Quality/analytical, Biological Analysis:

This topic is not addressed by the COFEPRIS guidelines.

Gap 8

Quality/analytical, Immunological Analysis:

This topic is not addressed by the COFEPRIS guidelines.

Gap 9

Quality/analytical, Impurities:

The guidelines do not address the fact that if significant differences are observed in the impurity profiles between the biosimilar and the original biologic, their potential effect on safety and efficacy should be evaluated.

Gap 10

Quality/Analytical, Stability Studies:

The COFEPRIS does not require head to head studies to evaluate the stability of the biosimilar as compared to the original biologic

Gap 11

Nonclinical, Pharmacokinetics:

This topic is not addressed by the COFEPRIS guidelines.

Gap 12

Nonclinical, Toxicology:

COFEPRIS allow single dose studies to evaluate toxicology, whereas the WHO specifies that toxicology should be evaluated over repeated doses.

Gap 13

Clinical, General Considerations:

The guidelines do not specify that the comparison of a biosimilar with the original biologic should begin with pharmacokinetic and pharmacodynamics studies.

Gap 14

Clinical, Efficacy:

The guidelines do not include detail on the clinical testing required to demonstrate biosimilarity. Rather, they allude to Ministry requirements, which are undefined.

Gap 15

Clinical, Safety:

This topic is not addressed by the COFEPRIS guidelines

Gap 16

Clinical, Immunogenicity:

The guidelines do not include detail on the clinical testing required to evaluate immunogenicity. Rather, they allude to Ministry requirements, which are undefined.

Gap 17

Indication Extrapolation:

The guidelines do not provide the same degree of detail as the WHO in describing when it is appropriate for the biosimilar to be approved for all the indications held by original biologic, regardless of whether those indications have been studied.

Overall country score as compared to peers

History of Policy

The biocomparables guidance was published in October 2011 by COFEPRIS in the Mexican Government’s official journal, Diaro Oficial de la Federación. The guidelines came into effect in April 2012.[1]

Although these guidelines only came into effect in 2012, in 2011 there were at least 23 non-originator biologicals already available on the Mexican market. Companies who registered these biologics prior to October 2011 (known colloquially as Biolimbos) are now mandated to conduct clinical trials to prove biosimilarity.[2]

Policy Guidelines

Biologics and Biosimilares Guideline

  • This guideline intended to assist those making biosimilar medicines by providing guidance on how to demonstrate that a biosimilar is comparable to an original biologic medicine for purposes of the submission of a marketing application.
  • First issued April 2012; Most recent update April 2012

Side by side comparison of each of the score components

For each of the 28 components of biosimilar policy evaluated, the specific wording in the FDA's biosimilar policy is listed, alongside the accompanying wording in the WHO policy (shown in the blue box).

Scope

[§ 3.0] Well-established and well-characterized biotherapeutic products such as DNA-derived therapeutic proteins. A well-established biotherapeutic is one that has been marketed for a suitable period of time with proven quality, safety, and efficacy.

Excludes vaccines, plasma-derived products, and their recombinant analogues.

[§ 3.53 in 6a] Biotechnological drug products.

Concept of Biosimilarity

[§ 4] A biosimilar is a biotherapeutic product that is similar in terms of quality, safety, and efficacy to an already licensed RP.

[§§ 3.36 in 6a, 4.46 in 6b, 3.45 in 6c] Biocomparability studies are the tests, assays and analyses required to demonstrate that a biosimilar has the same quality, safety, and efficacy characteristics as those of an Reference Product.

[§§ 3.54 in 6a, 0 in 6b, 3.85 in 6c] A biosimilar is a non-innovative drug product shown to be comparable to an Reference Product in terms of safety, quality, and efficacy.

Reference Product

[§ 7.0] The same RP should be used throughout the entire comparability exercise and it must be approved in the country/region in question (or, where the licensing country lacks an approved RP, approved and widely marketed in another jurisdiction with a well-established regulatory framework for, and experience in evaluation and post-market surveillance of, biotherapeutics).

[§ 8.1] As a general rule, the biosimilar product should be expressed and produced in the same host cell type as the RP. The applicant should determine the potential impact of changing the host cell on product quality, safety, and efficacy based on available evidence from public information and experience with previous use of the RP. The rationale for accepting a difference in host cell must be justified based upon sound science and clinical experience with the biosimilar or the RP.

[§§ 3.55, 3.56 in 6a, 3.85, 3.86 in 6c] The reference product is an innovative biotechnological product, registered with the Mexican Health Ministry, that is used as the reference for the registration of biosimilars.

[§§ 8.2.2 in 6a, 11.2.2 in 6b] The reference product may be supplied by its sponsor or acquired by the third party (that is authorized to conduct testing using it) in its original package and with a copy of the purchase invoice.

Formulation

[§ 8.1] The biosimilar manufacturer should assemble all available knowledge of the RP concerning the formulation used. The applicant should determine the potential impact of changing the formulation on product quality, safety, and efficacy based on available evidence from public information and experience with previous use of the RP. The rationale for accepting differences must be justified based upon sound science and clinical experience with the biosimilar or the RP.

Not addressed.

Route of Administration

[§ 5.0 ] Same as that of the RP.

[§ 5.12.7.2.2 in 6c] The applicant must identify the route of administration.

Dosage Form And Strength

[§ 5.0] Dosage form should be the same as that of the RP. Strength is not addressed.

[§ 8.1] The biosimilar manufacturer should assemble all available knowledge of the RP concerning the type of container closure system used. The applicant should determine the potential impact of changing the container closure on product quality, safety, and efficacy based on available evidence from public information and experience with previous use of the RP. The rationale for accepting a difference in container closure must be justified based upon sound science and clinical experience with the biosimilar or the RP.

[§§ 8.3.3 in 6a, 11.3.3 in 6b] The biosimilar must have the same dosage form, dose, and strength as that of the Reference Product.

General Considerations

[§ 8] The application must contain a full quality dossier for both the drug substance and the drug product.

To evaluate comparability, the manufacturer should carry out a comprehensive physicochemical and biological characterization of the biosimilar in head-to-head comparisons with the RP. All aspects of product quality and heterogeneity should be assessed.

[§ 5] Development of the biosimilar involves a stepwise approach starting with characterization and evaluation of quality attributes. Differences should always be explained and justified and may require additional data.

[§ 8.2] Investigation of differences between the biosimilar and the RP should be based on knowledge of the relationship between quality attributes and clinical activity of the RP and related products, the clinical history of the RP, and lot-to-lot differences of commercial lots of the RP.

[§§ 8.1.2 in 6a, 0, 11.1.1 in 6b] Clinical (and nonclinical and analytical) tests comparing the biosimilar and the Reference Product must be conducted by authorized third parties, research centers, or hospital institutions domestically (or, in exceptional cases, abroad).

[§§ 6.4.3, 6.4.4.1 in 6a] Clinical studies should include a “statistically representative Mexican population.”

[§§ 8.5.2.4 in 6a, 8.9.2.4 in 6b] The trial design depends on the nature of the Reference Product.

[§ 8.9.2.4 in 6b] The more that the biosimilar is well characterized and physicochemical comparability has been demonstrated, the less clinical evidence will be required.

Isolation of Drug Substance

[§ 8] Methods used to isolate RP drug substance for characterization must be justified and demonstrated to be appropriate. Studies must be carried out to demonstrate that product heterogeneity and relevant attributes of the active moiety are not affected by the isolation process.

Not addressed.

Physicochemical Analysis

[§ 8.2.1] The comparative physicochemical characterization should include the determination of primary and higher order structure and other biophysical properties using appropriate analytical methods (e.g. mass spectrometry, NMR).

The RP and the biosimilar are likely to contain a mixture of post-translationally modified forms, and appropriate efforts should be made to investigate, identify, and quantify these forms.

[§§ 8.4.2.4 in 6a, 11.8.3.3.5 in 6b] The physicochemical and biological studies must distinguish attributes of composition, primary structure, and higher order structure.

[§§ 8.4.2.5 in 6a, 11.8.3.3.6 in 6b] The higher order structure analysis must use analytical methods that allow elucidation of three-dimensional structure and chemical integrity, including post-translational modifications, to provide information about identity, heterogeneity, and purity of the biosimilar.

Biological and Immunological Analysis

Biological

[§ 8.2.2] Comparative evaluation with a biological assay complements the physicochemical analyses by confirming the correct higher order structure of the molecule.

Ideally, the biological assay will reflect the understood MoA of the protein and will thus serve as a link to clinical activity.

The use of a relevant biological assay(s) with appropriate precision and accuracy provides an important means of confirming that a significant functional difference does not exist between the biosimilar and the RP.

Immunological

[§ 8.2.3] When immunochemical properties are part of the characterization (e.g., for antibody-based products), the manufacturer should confirm that the biosimilar is comparable to the RP in terms of specificity, affinity, binding kinetics, and Fc functional activity, where relevant.

Not addressed.

Impurities

[§ 8.2.4] It is recognized that the comparison of the impurity profiles between the biosimilar and the RP will be generally difficult. Nevertheless, process- and product-related impurities should be identified, quantified by state-of-the-art technology, and compared between the biosimilar and the RP. If significant differences are observed in the impurity profiles, their potential impact on efficacy and safety, including immunogenicity, should be evaluated.

[§ 8.4.2.5 in 6a] The higher order structure analysis must use analytical methods that provide information about purity of the biosimilar.

Stability Studies

[§ 8.5] Head-to-head accelerated stability studies will be of value in determining the similarity of the products because they can reveal otherwise-hidden properties of a product that warrant additional evaluation. They are also important for identifying the degradation pathways of a protein product.

[§ 5.5.9.1 in 6a] Quality control must be demonstrated through stability studies, among other things.

Specifications

[§ 8.3] Specifications should capture and control important quality attributes known for the RP. Their setting should be based on the experience with the biosimilar and the results of the comparability evaluation, but should not be wider than the range of variability of the RP unless justified.

Specifications should be set as described in established guidelines and monographs, where these exist. Pharmacopoeial monographs may only provide a minimum set of requirements for a particular product, and additional test parameters may be necessary

[§ 5.5.9.1 in 6a] Quality control must be must be demonstrated by biological activity that is consistently within the limits established in the substance, intermediate, and finished product specifications.

[§ 5.12.7.1.3 in 6c] The applicant must submit specifications related to the biosimilar’s physicochemical properties, biological activity, purity, and impurity.

General

[§§ 9.1, 9.2] Nonclinical studies should use the final formulation intended for clinical use unless otherwise justified; the nonclinical evaluation encompasses a broad spectrum of PD, PK, and toxicity studies (per ICH S6); the amount of additional nonclinical data for safety and efficacy is dependent on product-specific factors (for example, quality, unknown or poorly understand MoA, significant toxicity, and/or narrow therapeutic index).

[§§ 8.1.2 in 6a, 0, 11.1.1 in 6b] Nonclinical (and clinical and analytical) tests comparing the biosimilar and the Reference Product must be conducted by authorized third parties, research centers, or hospital institutions domestically (or, in exceptional cases, abroad).

[§§ 8.4.2.3 in 6a, 11.8.3.3 in 6b] If the biosimilar is well characterized and physicochemical comparability between the biosimilar and the Reference Product has been demonstrated, the nonclinical evidence required will be less.

The biosimilar used in the pharmacology and toxicology studies must be analytically comparable to the Reference Product.

[§§ 8.4.2.10.1 in 6a, 11.8.3.12.1 in 6b] Safety tests will define the toxicological and pharmacological effects prior to clinical studies.

[§ 11.8.3.3.10 in 6b] The design of nonclinical tests depends on the nature of the Reference Product.

Pharmacology

[§ 9.2] In vitro studies: Assays like receptor-binding studies or cell-based assays should normally be conducted to establish comparability of PD activity.

In vivo studies: Animal studies should be designed to maximize information obtained; be conducted in relevant species (shown to possess PD and/or toxicological activity); and employ state-of-the-art technology. In vivo studies may not be needed if highly reliable in vitro assays that reflect clinically relevant PD activity of the RP are available.

[§ 8.4.2.10.4 in 6a] Biological activity and PD evaluation tests: the biological activity must be evaluated by in vitro, ex vivo, or in vivo assays. These assays must consider various factors such as biomarker selection and cell line use.

[§§ 8.4.2.10.2.1- 8.4.2.10.2.10 in 6a, 11.8.3.12.1 in 6b] Nonclinical in vivo safety studies must consider, among other things: (1) relevant species selection; (2) at least two relevant species (unless only one relevant species can be identified or the biological activity of the biosimilar is well-understood); (3) use of transgenic animals expressing the human receptor when there are no relevant species; (4) toxicity evaluation in one species; (5) use of animal models of the disease in some cases.

[§ 11.8.3.3.1 in 6b] The biosimilar used in pharmacology and toxicology studies should be analytically comparable to the Reference Product.

[§ 11.8.3.12.2 in 6b] Biological activity should be evaluated through in vitro, ex vivo, or in vivo studies, taking into consideration: (1) the selection of biomarkers according to their relevance to demonstrate therapeutic efficacy; (2) the use of cell lines derived from mammals for predicting specific aspects of in vivo activity; and (3) the use of cell lines or primary cultures to examine the direct effects on cell phenotype, proliferation, cellular activation, and binding to target molecules.

For monoclonal antibodies, the immunological properties of the specific binding to the target molecule, specific antigenicity, complement bond, mediated cytotoxicity, and any other antibody reactivity or cytotoxicity towards human tissues other than the intended target should be analyzed.

Immunogenicity testing in animals must be performed only in studies of repeated dose toxicity to assist the interpretation of these studies and only when the relevance of the species is demonstrated.

Pharmacokinetics

[§ 9.2] Nonclinical evaluation normally encompasses a broad spectrum of studies, including PK studies. The amount of data is highly dependent on the product and class-related factors.

Not addressed.

Toxicology

[§ 9.2] Comparative repeat-dose toxicity in relevant species (including TK measurements and antibody responses); local tolerance may need to be evaluated depending on the route of administration.

Safety pharmacology, reproductive toxicology, genotoxicity, and carcinogenicity studies are generally not needed unless cause for concern (based on repeat dose toxicity study or local tolerance study, for example).

[§§ 8.4.2.10.1, 8.4.2.10.8, 8.4.2.10.10, 8.4.2.10.12 in 6a, 11.8.3.12 , 11.8.3.14-11.8.3.18 in 6b] Biosimilars that are structurally and pharmacologically comparable to the Reference Product and for which there is broad experience in clinical practice will require less extensive toxicological studies.

When possible, single dose studies must include TK. For biosimilars that induce long-lasting pharmacological and toxicological effects, an animal group must be monitored until reversibility is demonstrated.

The duration of nonclinical trials must be sufficient to detect relevant differences in toxicity and immune responses between the biosimilar and the Reference Product.

Results of studies such as pharmacological safety, reproductive toxicology, mutagenicity and carcinogenicity will be required only if they are necessary based on the results from the repeated dose studies.

PK and PD

[§ 10] Clinical studies should be designed to demonstrate comparable safety and efficacy of the biosimilar to the RP and therefore need to employ strategies that are sensitive enough to detect relevant differences. The comparability exercise is a stepwise procedure that should begin with PK and PD studies followed by the pivotal clinical trials.

If any relevant differences between the biosimilar and the RP are detected, the reasons need to be explored and justified. If this is not possible, the new product may not qualify as a biosimilar and a full licensing application should be considered.

[§§ 8.6.4.1 in 6a, 11.11 in 6b] PK studies can be conducted with a single dose or multiple doses, must have acceptance ranges based in clinical criteria, and must include a population that is a “proper option” for the biosimilar. Trial design must be fully justified.

[§§ 8.6.4.2 in 6a, 11.12 in 6b] PD studies must use biomarkers selected based on their relevance to demonstrating efficacy, have a duration and design that is justified, and include a population that is a “proper option” for the biosimilar.

Combined PK/PD studies can provide useful information about the relationship between exposure and effect.

Efficacy Assessment

[§ 10.1] The PK profile should always be investigated. This is best achieved with single-dose, cross-over studies in a homogenous study population using a dose where the sensitivity to detect differences is largest. Where there are dose and time-dependent pharmacokinetics, it may be necessary to perform a comparative multi-dose study.

The traditional equivalence range is often used. If this range is not met, the biosimilar may still be considered similar with sufficient evidence from other comparisons.

[§ 10.2] PD studies may be advisable prior to efficacy and safety trials if differences of unknown relevance have been detected in PK studies. In many cases, PD parameters are investigated in the context of combined PK/PD studies.

[§ 11.9.2.8 in 6b] “Clinical studies must have addition to what the Ministry requires, if applicable, studies of efficacy” [sic].

Safety

[§ 10.3] Usually, clinical trials are required to demonstrate similar efficacy. Confirmatory PK/PD may be used in lieu of efficacy trials provided there is sufficient knowledge of the PK/PD profile of the RP, at least one PD marker has a well-established relationship to efficacy, and the relationship between dose/exposure, the relevant PD marker, and response/efficacy of the RP is established.

[§ 10.4] Similar efficacy means similar treatment effects are achieved at the same dosages.

Similar efficacy will usually have to be shown in a controlled, adequately powered, study that is, preferably, double blind. Potential differences between the products should be investigated in a sensitive and well-established clinical model.

Not addressed.

Immunogenicity

[§ 10.5] Safety data should be obtained in a sufficient number of patients to provide a comparison of type, frequency, and severity of adverse events. Safety data from the efficacy trials may be sufficient for this purpose (or may need to be extended), but in any case additional monitoring is usually necessary after approval.

[§ 11.9.2.8 in 6b] “Clinical studies must have addition to what the Ministry requires, if applicable, studies of … immunogenicity” [sic].

Extrapolation of Indications

[§ 10.6] Immunogenicity should always be investigated in humans prior to authorization, because animal data are usually not predictive and because it could affect PK, PD, or safety. Generally, the data from a comparative efficacy trial will be sufficient prior to market authorization, subject to appropriate post-market pharmacovigilance for rare adverse events or where clinically meaningful or serious antibody development has been encountered in the RP or substance class.

In the case of chronic administration, one year of data prior to market authorization is usually appropriate.

[§ 10.6] Antibody assays need to be validated for their purpose. Detected antibodies need to be characterized for their clinical implications with special attention to the possibility of interaction with endogenous protein.

[§§ 6.4.3, 6.4.3.1, 8.5.2.9 in 6a, 5.12.7.1.5 in 6c] Therapeutic indications must be based on nonclinical and clinical data. A biosimilar can be approved for use in other clinical indications (for which the Reference Product is not approved) if clinical studies provide scientific justification (as evaluated by Mexican health agencies).

Risk Management Plans

[§ 10.7] Extrapolation to other approved indications of the RP may be possible if all of the following conditions are met: (1) a sensitive clinical test model has been used that is able to detect potential differences between the products; (2) the clinically relevant MoA and/or receptors are the same (or, if the MoA is different or not known, a strong scientific rationale and additional data will be needed); (3) safety and immunogenicity of the biosimilar have been characterized and there are no special safety issues expected with the extrapolated indication; and (4) if the efficacy trial used a non-inferiority study design and demonstrated acceptable safety and efficacy of the biosimilar compared to the RP, the applicant should provide convincing arguments that this finding can be applied to the extrapolated indications.

If these prerequisites for extrapolation of efficacy and safety data of the biosimilar to other indication(s) of the RP are not fulfilled, the manufacturer will need to submit its own clinical data to support the desired indication(s).

[§§ 6.4.8, 7.1.2.1 in 6a, 5.12.7.6, 7.2.4.3.2 in 6c] The applicant must present an RMP that describes the activities and interventions designed to detect, characterize, and prevent identified risks. It must include a PV program (an early postmarket study of three years or “intensive” PV) and a risk minimization plan to reduce risks.

Interchangeability

[§ 11] Data from pre-authorization clinical studies are usually too limited to identify all potential unwanted effects of a biosimilar, and in particular, rare adverse events.

Therefore, further close monitoring of the clinical safety of these products in all approved indications and continued benefit-risk assessment is necessary in the post-market phase.

A safety specification and PV plan are required at the time of submission, describing safety issues for the RP, the class, and/or the biosimilar.

Any special safety monitoring imposed on the RP or product class should be incorporated into the PV plan for the biosimilar, unless there is a compelling justification not to do so.

The regional authority should provide a framework establishing the ability to ensure specific identification of the biosimilar (i.e., traceability). There should be a legal framework adequate to identify any biotherapeutic marketed in its territory that is the subject of adverse event reports.

[6b] The term “interchangeability” expressly applies to small molecule products, not biologics, in the draft Mexican regulations.

Naming
Not addressed specifically. To be determined by national authorities.

[§ 6, bullet e] Biosimilars “are not generic medicines; and many characteristics associated with [that] authorization process generally do not apply.”

[§ 12] The biosimilar should be clearly identifiable by a unique brand name, and the prescribing information should be as similar as possible to that of the RP except for product-specific aspects such as different excipients.

Note: Naming and interchangeability should be treated as separate issues. WHO has recommended a generic name plus numbering system. Naming, per se, is not about the basic science of interchangeability.

[§ 6.4.6.1 in 6a] The biosimilar’s labeling must include the International Common Denomination (ICD), the generic name established by the WHO.

[§§ 3.28 in 6a, 3.31, 7.2.4.4.1.2, 7.2.4.4.2.2 in 6c] Labels also must contain the brand/trademarked name.

Labeling

[§ 12.0] A biosimilar should be clearly identifiable by a unique brand name. Where an international non-proprietary name (INN) is defined, it should be stated. The WHO’s policy on INNs should be followed. The provision of a lot number is essential and critical for traceability.

[Note: In July 2014, the WHO issued a proposal for unique biologic identifiers (BQs) that could be added to the INNs of biologics, whether innovative or biosimilar. See INN Working Doc. 14.342 (July 2014).]

[§§ 6.4.6.1 in 6a, 5.12.7.4, 7.2.4.4.1.2, 7.2.4.4.2.2 in 6c] Labels must contain the brand name, the ICD established by the WHO, initials M.B.B. and the name of the Reference Product, pharmaceutical form, concentration, manufacturer and its origin, formula, route of administration, content, doses, information concerning preservation and storage, warning and precautionary information,  batch number, date of expiration, place of packing, distributor information and, if applicable, importer information.

Considerations for Quality by Design

[§ 12] The prescribing information for the biosimilar should be as similar as possible to that of the RP, except for product-specific aspects, such as different excipient(s). This is particularly important for posology and safety-related information, including contraindications, warnings, and adverse events.

If the biosimilar has fewer indications than the RP, the related text in various sections may be omitted unless it is considered important to inform doctors and patients about certain risks (e.g. because of potential off-label use). In such cases it should be clearly stated in the prescribing information that the biosimilar is not indicated for use in the specific indication(s) and the reasons why.

The national regulatory authority may choose to mention the biosimilar nature of the product and the studies that have been performed with the biosimilar, including the specific RP, in the product information.

The national regulatory authority may choose to include instructions for the prescribing physician on how to use biosimilar products.

[§ 5 in 6a] Mexico has good manufacturing practices requirements that apply to biosimilars.

Footnotes

[1] Source: http://www.gabionline.net/Guidelines/Mexican-guidelines-for-biocomparables

[2] Source: http://www.fdanews.com/articles/170140-new-mexican-biosimilar-rules-on-biosimilars-take-effect-in-mexico