Responsabilities of Sanitary Registration Holders of Pharmaceutical Products
Q.F. Ana Susana Rojas Avalos
Regulatory Intelligence Consultant
SCR Consulting Peru
The Sanitary Registration is a legal instrument granted by the Ministry of Health, which,
according to Law No. 29459 “Law of Pharmaceutical Products, Medical Devices
and Health Products” and Supreme Decree N° 016-2011 “Regulation for the
Registration, Control and Sanitary Surveillance of Pharmaceutical Products,
Medical Devices and Health Products” and its respective amendments, entitles
its holder to manufacture, import, store, distribute, commercialize, promote, dispense,
sell or use them.
It is then that the holder of the sanitary registration of a pharmaceutical product assumes
legal and administrative responsibilities in Peru, upon registering a pharmaceutical
product with the health authority, DIGEMID.
Let’s understand that this responsibility to Peruvian society is assumed when presenting
a sanitary registration dossier before DIGEMID with original and reliable documents that
prove the product under registration or renewal complies with all the requirements of
Peruvian regulations, as well as with what is established by the reference
pharmacopoeias and the guidelines set by High Health Surveillance Countries. Therefore,
ensuring that the pharmaceutical product in question complies with the principles of
safety, efficacy, and quality.
However, in order for the products to continue complying with the above-mentioned
principles, a company, before being the holder of the sanitary registration of a
pharmaceutical product, must first have a pharmaceutical establishment registered on
Peruvian territory, that is to say, it must have authorization to operate as a Drugstore
or Laboratory in Peru. And for this, according to the Supreme Decree 014-2011
“Regulation of Pharmaceutical Establishments” and its respective
amendments, it must be technically directed by a duly qualified Pharmaceutical
Chemist, who must request its registration as Technical Director of such pharmaceutical
establishment before the DIGEMID. Once with the proper management of the
Pharmaceutical Chemist, the warehouse must accredit the certification in Good Storage
Practices or Good Manufacturing Practices, certification that will be granted by the same
DIGEMID, as appropriate. It is then that, the pharmaceutical establishment, having
these previous aspects, will be accredited to provide the products, an adequate storage,
in order to preserve its principles of safety, efficacy and quality, and it is, therefore, that
it may request to be the holder of a pharmaceutical product.
Additionally, with products already in stock, whether under ownership or not, the
pharmaceutical establishment must be duly certified in Good Distribution and
Transportation Practices (according to Ministerial Resolution No. 833-
2015/MINSA), to guarantee that the products will be properly preserved during the
distribution and transportation processes, both the transportation that goes from the
supplier’s supply and ends at the establishment’s warehouse; as well as the subsequent
distribution from the pharmaceutical establishment’s warehouse to the distributors or
marketers of the product. All this scenario will support the pharmaceutical establishment
before the Peruvian society and the Ministry of Health, since the application of GSP, GMP
and/or GD&TP, ensures that the pharmaceutical company follows a quality system, and
that in case of any observation in the product, there will be a responsible legal and
technical figure to provide explanations.
Thus, a pharmaceutical establishment, whether or not it holds the sanitary registration
of pharmaceutical products, assumes responsibility for the medicines it acquires
(whether through importation, local manufacturing, or local purchase), stores, markets,
promotes, or distributes. However, pharmaceutical establishments that hold the sanitary
registration of pharmaceutical products will assume a series of additional responsibilities.
The following is a more detailed explanation of these responsibilities:
1. Sanitary Registration, the first responsibility of the sanitary registration holders of
pharmaceutical products is in relation to the sanitary registration itself. With the
submission of the dossier requesting the sanitary authorization and the subsequent
granting of the sanitary registration number through the Directorial Resolution, this
is not all in relation to this point. The sanitary registration must be renewed every 5
years according to the “Regulation for the Registration, Control and Sanitary
Surveillance of Pharmaceutical Products, Medical Devices and Health
Products” and its respective amendments, so the Technical Director must have
a programming plan for the re-registration of the products, under the ownership of
the company.
In addition, the technical information on efficacy, safety and quality of the initial
dossier of the products may undergo changes, either generated by the same
company that supplies the products or due to updates of the pharmacopoeias used
as reference; likewise, the DIGEMID may issue Safety Alerts that require
modifications in the formulation, labeling, inserts and/or technical data sheets,
therefore it is also the obligation of the Technical Director to keep the dossier updated
for the health authority.
Additionally, in relation to the request for sanitary registration, it is important to
mention that if the pharmaceutical product is manufactured in a country that is not
considered a high sanitary surveillance country, the pharmaceutical establishment
must previously process at the DIGEMID the pre-liquidation of the laboratory
manufacturing the product, a necessary document that is also part of the registration
file, in these cases, until the Health Authority audits the facilities of the laboratory in
question and issues the respective Directorial Resolution of Good Manufacturing
Practices.
2. Import, the company holding the sanitary registrations must prepare an import
dossier for the customs clearance of the products entering the national territory,
which must include the Certificates of Analysis, shared by the manufacturers, for
each batch of product entering the national territory, as well as all the technical
documentation, such as the updated Sanitary Registration Directorial Resolutions;
and administrative documentation, such as the Commercial Invoice (also called
invoice), the packing list and the copy of the resolution document, this last one as a
document issued by the VUCE (which is issued together with the Directorial
Resolution of the Sanitary Registration).
Once the documentary verification is completed, Peruvian CUSTOMS electronically
issues the respective Customs Declaration of Goods (CDG), which is the final
document that must be filed with the product’s import file.
It is important to specify that in addition to the above documents, pharmaceutical
products containing controlled substances, in accordance with the provisions of
Supreme Decree No. 023-2001-SA: “Regulation of Narcotic Drugs and
Psychotropic Narcotic Drugs Subject to Inspection”, must have in the import
file the Official Import Certificate and the Directorial Resolution of authorization of
internment.
Other pharmaceutical products that require specific documents are products derived
from human plasma, for which Supreme Decree No. 016-2011 and its
respective amendments state that the establishment must present a certificate of
HIV, Hepatitis B and C negativity. Meanwhile, for biological products derived from
bovine, ovine and caprine livestock, a certificate of negativity of bovine spongiform
encephalopathy must be presented.
3. Pharmaceutical Products with controlled substances, the Drugstores importing
controlled pharmaceutical products, in addition to what is established in the:
“Regulation of Narcotic Drugs and Psychotropic Narcotic Drugs Subject to
Inspection”, must communicate to the DIGEMID their plans to import
pharmaceutical products containing the substances included in the above-mentioned
Regulation. Such communications must be made during the first three months of the
calendar year prior to that in which the company intends to import.
The Official Import Certificate and the Directorial Resolution for entry authorization
must be requested in advance through a Sworn Statement before DIGEMID. The
entity must issue this document within 15 working days. These certificates are valid
for 180 calendar days. It is important to note that they are valid for a single shipment
only. Additionally, it is essential to mention that partial imports under the same
Official Certificate are not allowed.
Also, within fifteen (15) days after the goods have been nationalized, in case an
importation has been made, the pharmaceutical establishment must submit to the
DIGEMD a photocopy of the respective invoice, as well as the Single Customs
Declaration (SCD) of Importation. It is important to note that the DIGEMID will not
authorize a new import as long as the pharmaceutical establishment does not comply
with submitting the documents to the health authority.
At the end of the year of importation, drugstores must inform the DIGEMID until
January 31 of the total imports of medicines with controlled substances made, the
annual consumption and the balance as of December 31 of the previous year.
Therefore, drugstores that own pharmaceutical products containing controlled
substances must plan all this management and include it in their standard operating
procedures. Additionally, within the management of these products, it is implied that the
pharmaceutical establishments are obligated to keep in the books and with the
formalities implied in the above mentioned “Regulation of Narcotic Drugs and
Psychotropic Narcotic Drugs Subject to Inspection”, the registry of their stocks,
as well as the accounting related to their consumption.
Finally, with reference to these products, drugstores that sell medicines containing
controlled substances must submit quarterly balance sheets of the sales made. The
balance sheets must be closed on the last working day of the corresponding month and
must be submitted, under responsibility, within fifteen (15) calendar days following the
closing date.
4. Retention Samples or Counter Samples, drugstores that are holders of imported
products should consider in addition to their general storage areas and in accordance
with the stipulations of Ministerial Resolution 132-2015/MINSA: “Manual of Good
Storage Practices for Pharmaceutical Products, Medical Devices and Health
Products in Laboratories, Drugstores, Specialized Warehouses and Customs
Warehouses”, the area for Retention Samples or Counter Samples, to store a
representative amount of products from each batch, series or code of identification of
pharmaceutical products that enter the warehouse after importation.
5. Inquiries, the holder of the sanitary registration is responsible for providing the health
authority:
– Certificate of analysis corresponding to the lot or series inquired;
– The primary or secondary standards of the Active Pharmaceutical Ingredient(s),
along with the respective certificates of analysis of the standards, which shall be valid
for no less than 6 months at the time of submission of such requirement.
In the caseof secondary standards, it must indicate the batch number of the primary standard
with which it was traced and include a comparison pattern, when applicable.
The delivery of the above mentioned is indistinct to the fact that the products have been
inquired at their warehouses or at the warehouses of the distributors of the products. It
is then, also, that the holder of the sanitary registrations inquired, is responsible for
replacing the samples inspected in the establishments in a term not greater than 60
calendar days after the inspection has been made and notified by the establishment
where the inspection was carried out.
6. Stock depletion, the sanitary registration holder is the only one who can request to
DIGEMID the authorization for the stock depletion of the products, which due to some
point regulated by Supreme Decree No. 016-2011 and its respective
amendments, cause the depletion of units circulating in the market, and which are
different from the last labeling or inserts authorized in its sanitary registration.
7. Price Observatory, In the framework of the “Law of Pharmaceutical Products, Medical
Devices and Health Products” to provide a price system to the Peruvian society, the
monthly declaration of the prices of pharmaceutical products must be made by the
pharmaceutical establishments to the DIGEMID, whether or not they are the holders of
the sanitary registrations, since such responsibility is given for all the products marketed
by a pharmaceutical establishment during each month.
8. Pharmacovigilance, the sanitary registrations holders of pharmaceutical products, will
assume general commitments for their products, in the field of Pharmacovigilance, as
any pharmaceutical establishment; which are materialized in the implementation of
processes within the company. These processes, according to the Ministerial
Resolution 1053-2020/MINSA: “Manual of Good Pharmacovigilance Practices”,
are detailed as follows:
– Compilation, coding and registration of a Suspected Adverse Drug Reaction (ADR)
in a database;
– Notification and Submission of a SAR;
– Management of requests required by DIGEMID;
– Management for the adoption and monitoring of DIGEMID regulatory measures
for safety reasons;
– Qualification;
– Archive of all pharmacovigilance documents.
Furthermore, the establishments as holders of the sanitary registration of
pharmaceutical products, have greater commitments in the Good Pharmacovigilance
Practice System; these are going to be given in the implementation of the following
specific processes:
– Monitoring, evaluation, classification and duplicate detection of an ADR;
– Pharmacovigilance database management;
– Permanent evaluation of the safety profile of pharmaceutical products;
– Actions to be taken based on the results of the safety profile evaluation;
– Elaboration, approval and submission of Periodic Safety Reports;
– Elaboration, implementation and monitoring of Risk Management Plans;
– Urgent actions taken for safety reasons;
– Investigation of pharmaceutical product safety issues;
– Management of post-authorization studies;
– Development of self-inspections to pharmacovigilance processes.
Likewise, within the pharmaceutical establishment, regardless of whether or not it is the
owner of the products it markets, there must be a person in charge of
Pharmacovigilance; this responsibility can be assumed by the Technical Director, as long
as he/she is properly qualified in Pharmacovigilance knowledge. Therefore, the person
in charge of Pharmacovigilance and/or the Technical Director himself will be the one who
implements the Good Pharmacovigilance Practices System within the pharmaceutical
establishment, which implies the respective certification in this area, granted by the
DIGEMID.
It is then, that through the analysis of the responsibilities of the holders of the sanitary
registrations of pharmaceutical products, given in the executive management and by the
review of the different regulations of application for the sanitary registration and in the
pharmaceutical establishments in Peru; it can be commented that being a
pharmaceutical company, the holder of the sanitary registrations of pharmaceutical
products, assumes greater responsibilities with the health authority of Peru; as they are
the legal figures that represent the product in this country, whether the manufacture
occurs in national territory or outside of Peru. This means that they assume legal
commitments to the Peruvian society, since, as owners, they are responsible for assuring
that all the documentation accompanying a pharmaceutical product, for its registration
and subsequent traceability, is reliable. Likewise, the company that owns a
pharmaceutical product assumes the responsibility of representing this health product,
which must comply and preserve the principles of safety, efficacy and quality, since it is
intended for use in or by people, in order to improve their quality of life. For this reason,
in case of any observation either in the quality or in the safety and efficacy of the
products, it will be the pharmaceutical company holder of the sanitary registration who
will act responsibly, in a timely and proper way.