Regulatory Considerations in The Requirements for the Sanitary Registration of Pharmaceutical Products in Peru
Q.F. Luz Marianee Castañeda Saavedra
Quality and Regulatory Affairs Specialist
SCR Consulting Peru
BACKGROUND OF THE REGULATION OF THE SANITARY REGISTRATION OF PHARMACEUTICAL PRODUCTS
In the late 1990s, with the enactment of General Health Law No. 26842 in Peru, it
was established that the registration of medicines in the Sanitary Registry was
automatic, requiring only the submission of the documents outlined in the mentioned
regulatory document. The Peruvian health authority had a maximum period of 7 business
days to issue the document that certifies the registration number. This was a significant
milestone in the registration of medicines, as until the enactment of Law No. 29459:
“Law of Pharmaceutical Products, Medical Devices, and Health Products”
published in 2009, a total of 17,442 medicines were registered with DIGEMID (as cited
by Dr. Víctor Dongo in the analysis conducted on LAW No. 29459 – LAW OF
PHARMACEUTICAL PRODUCTS, MEDICAL DEVICES, AND HEALTH PRODUCTS,
published in the Peruvian Journal of Experimental Medicine and Public Health in 2009),
generating that due to the high demand for registration processes, it became impossible
for the health entity to carry out an adequate technical evaluation; which would later
result in the entrance of a large number of drugs that did not comply with the minimum
conditions necessary to guarantee their quality, safety and efficacy.
It is through the enactment of the mentioned Law of Pharmaceutical Products,
Medical Devices and Health Products, that a classification of products is established,
as follows:
Being that in turn, medicines are classified into:
1. Pharmaceutical products
2. Diagnostic agents
3. Radiopharmaceuticals
4. Medicinal gases.
As for pharmaceutical products drugs, 3 categories are established:
* Reference Summary of Product Characteristics and Leaflet of the PAVS.
**Clinical and pre-clinical studies as applicable.
(Table 1. Categories of pharmaceutical products (PP) and efficacy and safety
requirements taken from the publication “Efficacy and safety in the new
regulation of pharmaceutical products in Peru”; published by INS)
Among these categories there are differences in the evaluation criteria, which assurance
the safety, quality and efficacy of a pharmaceutical product before granting the Sanitary
Registration.
REQUIREMENTS FOR OBTAINING THE SANITARY REGISTRATION OF
PHARMACEUTICAL PRODUCTS:
With the approval of the “ Regulation for the Registration, Control and Sanitary
Surveillance of Pharmaceutical Products, Medical Devices and Health
Products”, through Supreme Decree No. 016-2011-SA, new regulations, foundations
and technical criteria are established for the evaluation of medicines based on evidence
of efficacy, quality and safety.
The general requirements for the inscription of pharmaceutical products are established,
through Article 40° of Supreme Decree No. 016-2011-SA. In the following table
presents the list of requirements for each category of pharmaceutical product:
* This requirement will be applied after four years from the effective date of the
corresponding regulations.
** Currently, we have a list of medicines for the requirement of the presentation of
therapeutic equivalence studies to demonstrate the interchangeability regulated by
Supreme Decree No. 024-2018-SA “Regulations governing the interchangeability of
medicines”. Published: September 15, 2018. This means that not all pharmaceutical
products are required to submit these studies.
*** The Certificate of Free Sale will only be accepted if the Regulatory Agency of the
country where the pharmaceutical product was manufactured does not issue a Certificate
of Pharmaceutical Product.
**** The efficacy and safety of the pharmaceutical product will be supported through
studies, if it presents a different pharmaceutical form, quantity of Active Pharmaceutical
Ingredient-API or route of administration to that of the National Unique List of Essential
Medicines or to that authorized in a High Sanitary Surveillance Country, for category 1
and 2 pharmaceutical products, respectively.
It is important to note that obtaining the Sanitary Registration ensures that the
pharmaceutical specialties marketed in Peru are safe, effective, and of proven quality
even before entering the national territory, thereby preventing the entry of products
manufactured under conditions below the minimum standard, which could be dangerous
for patients.
IMPORTANT ANNOTATIONS TO CONSIDER IN THE REGISTRATION PROCESS OF
PHARMACEUTICAL PRODUCTS
It is important to note that the CTD format (The Common Technical Document –
International Conference on Harmonization (ICH)) is not accepted for the purpose of
registering pharmaceutical specialties. Therefore, the manufacturer must adapt its
documentation to meet each requirement and present it in an official document signed
by the manufacturer or the product licensee. Below are some annotations to consider in
the registration process of these products:
– TECHNICAL SPECIFICATIONS AND ANALYTICAL TECHNIQUES OF THE
API(S), EXCIPIENTS AND FINISHED PRODUCT.
Generally, the technical specifications of the Active Pharmaceutical Ingredient,
excipients, and finished product must comply with the reference pharmacopoeias
recognized by Peruvian drug regulations. However, if these do not meet this
requirement, different technical specifications from the reference pharmacopoeias may
be accepted, provided that they are approved by High Sanitary Surveillance Countries.
In the case of the analytical technique for the Active Pharmaceutical Ingredient,
excipients, and finished product, the manufacturer may adhere to a reference
pharmacopoeia or declare it as an internal one. If the latter is the case, the
corresponding validation for the finished product must be provided.
– TECHNICAL SPECIFICATIONS OF THE SECONDARY AND PRIMARY PACKAGING
MATERIALS
The specifications must be issued by the manufacturer of the product, however, the
regulatory authority DIGEMID accepts addenda and/or clarifications to these documents,
which must be submitted by the supplier of the secondary and primary packaging
material.
– VALIDATION OF THE ANALYTICAL TECHNIQUES SPECIFIC TO THE FINISHED
PRODUCT
Must comply with the guidelines established in THS No. 147-MINSA/2019/DIGEMID:
“Technical Health Standard that Regulates the Minimum Information to be
contained in the Document of Validation of Proprietary Analytical Techniques.”
approved through Ministerial Resolution No. 234-2019/MINSA.
– FLOWCHART AND VALIDATION OF THE MANUFACTURING PROCESS,
IDENTIFYING CRITICAL ATTRIBUTES
As mentioned in the notes of the table presented above, to date this requirement is not
demanded by DIGEMID, it is understood that it will be effective until the enactment of
the corresponding regulations.
– STABILITY STUDIES
The presentation of stability studies must be in compliance with the guidelines
established in the Sanitary Directive No. 031-MINSA/DIGEMID-V.01 – Sanitary
Directive that regulates the Stability studies of medicines, approved by
Ministerial Resolution No. 805-2009/MINSA.
An important consideration to take into account for this requirement is that, in February
2022, will be approved the THS N° 182-MINSA/DIGEMID-2022: “Technical Health
Standard that regulates Stability Studies of Pharmaceutical Products”, which
establishes new dispositions that regulate the development of stability studies of
pharmaceutical specialties and the information that must be included in the document
required for the evaluation of these studies.
This Technical Standard will become effective 18 months from the day following its
publication, so that in August 2023, the presentation of stability studies must start
complying with the provisions of this document.
– THERAPEUTIC EQUIVALENCE STUDIES TO DEMONSTRATE
INTERCHANGEABILITY
Two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent
or pharmaceutical alternatives and their bioavailabilities, in terms of peak (Cmax and
Tmax) and total exposure (area under the curve (AUC)), after administration at the same
molar dose under the same conditions, are similar enough that their effects can be
expected to be essentially the same, according to the provisions set forth in Annex No.
01 of S.D. 016-2011/SA: Regulations for the Registration, Control and Sanitary
Surveillance of Pharmaceutical Products, Medical Devices and Health Products.
It should be noted that for a generic drug to be considered interchangeable, it must be
therapeutically equivalent to the comparable product. However, there are
pharmaceutical products for which interchangeability is ensured through compliance with
GMP and their technical specifications, and therefore do not require therapeutic
equivalence studies.
– DRAFT OF SUMMARY OF PRODUCT CHARACTERISTICS AND LEAFLET
The information contained in these documents must comply with established in Articles
48°, 49° and Annex No. 03 of the regulation approved by Supreme Decree No. 016-
2011-SA, as well as the respective sanitary alerts issued periodically by the Peruvian
Health Authority.
This information must be based on data sheets and inserts authorized in High Sanitary
Surveillance Countries, EMA or WHO and on clinical trials.
– PROJECT OF ARTWORKS IN SPANISH LANGUAGE OF THE SECONDARY AND
PRIMARY PACKAGING
The information contained in the labeling must comply with established in Articles 17°,
44°, 45° and 47° of the regulation approved by Supreme Decree No. 016-2011-SA.
– CERTIFICATE OF PHARMACEUTICAL PRODUCT (CPP)
This document must be in compliance with the WHO model, it must also contain the
formulation of the product, in case it does not contain this last information, this
information must be attached to the CPP, which must be properly endorsed by the Health
Authority of the country that issued it and apostilled, when applicable.
This certificate must not be older than 2 years from the date of issue.
The apostille of the document applies in case the Health Authority that issued the
document is not in the “List of Competent Authorities for the Emission of the
Certificate of Pharmaceutical Product or Certificate of Free Sale of Products or
Devices”, approved with Directorial Resolution No. 169-2014-DIGEMID-DG-
MINSA.
In case of being a product manufactured by order, it is not necessary to submit the CPP.
– CERTIFICATE OF GOOD MANUFACTURING PRACTICES (GMP)
The certificate must not be older than 2 years from the date of issue.
The manufacturing area must be included in the certificate for which the Sanitary
Registration is being requested.
The GMP certificate must be issued by the Peruvian National Sanitary Authority
(DIGEMID) or by a High Sanitary Surveillance Country (PAVS), if the document does not
have either of these two certifications, the respective certification must be requested to
the Dirección de General de Medicamentos, Insumos y Drogas (DIGEMID) and be
properly included in the list periodically provided by the same DIGEMID, according to
what is established in the
Sanitary Directive No. 001-MINSA/DIGEMID V.01 – Sanitary Directive
“Technical criteria for the evaluation of a dossier of pharmaceutical products”.
FINAL NOTES
The following table details the evaluation deadlines, validity of the Sanitary Registration
and complexity of the process to obtain the Sanitary Registration.
Notes:
(*) Pharmaceutical products which active pharmaceutical ingredients or combinations
are included in the National Unique List of Essential Medicines.
(**) Pharmaceutical products whose active pharmaceutical ingredients or combinations
are not in the National Unique List of Essential Medicines, but are registered High
Sanitary Surveillance Countries.
(***) Pharmaceutical products whose active pharmaceutical ingredients or combinations
are not considered in categories 1 and 2.
(1) The approval time for the Sanitary Registration stated in this document is the legal
evaluation time stated in the Peruvian regulation; however, the health authority of this
country may take more time in the evaluation of the registration applications, being able
to take up to years of evaluation. This may depend on the complexity of the sanitary
registration dossier, as well as on the number of dossiers that the DIGEMID has at that
date.
Through the present technical analysis, it can be commented that in the experience it is
evidenced that Category 1 foreign products present a low to medium complexity, while
those of Category 2 present a medium complexity, and those of Category 3 usually
contemplate a high complexity.
In addition, this analysis includes the main regulatory aspects for the proper evaluation
of a dossier of pharmaceutical specialties, taking into account the particularities of each
requirement. However, it should be considered that the technical dossiers are provided
by different manufacturers worldwide, contemplating countries with stricter sanitary
regulations than others, which may lead to a more rigorous evaluation of the documents
in order to discriminate unsuitable products, with the purpose of offering in the Peruvian
market pharmaceutical specialties with the minimum necessary standards of quality,
efficacy and safety, guaranteeing the adequate use and administration in patients.