REFERENCE MANUAL FOR SANITARY REGISTRATION

OF ORPHAN DRUGS IS APPROVED

Exempt Resolution N1,751.- Santiago, July 11th 2012.- In view of: the
exempt resolution N515, dated April 2nd 2004, which establishes the Basis of
National Drugs Policy in the context of the Health Care Reform; the agreement
reached in the Orphan Drugs Workshop of year 2011, integrated by Pharmaceutical
Chemists from the National Drugs Department of the Public Health Institute of Chile
and from the National and International Pharmaceutical Industry; the e-mail dated
May 11th 2012 sent by the Head of the National Drugs Department to the Legal
Section of this Institute; the memorandum N670 dated July 4th 2012 from the
National Drugs Department; and
Considering:
First: The existence in the country of patients suffering from low prevalence
diseases, as well as suffering from severe, debilitating and chronic diseases, which
pose an imminent threat to life;
Second: The necessity of providing drugs useful for the treatment of these
diseases, and of reducing the examination terms for the corresponding registration
applications, in order to guarantee the population a quick access to these drugs; and
Bearing in mind: The power granted to me by articles 94th and 102nd of the
Sanitary Code; the Constitutional Organic Law of General Bases of the States
Administration; the Regulations to the National Control System of Pharmaceutical
Products for Human Use, approved by supreme decree N3 of year 2010, by the
Health Care Ministry; articles 60th and 61st, item a) of the statutory decree N1 of
year 2005, which lays down the revised, coordinated and systematized text of the
decree-law N2,763 of year 1979, and laws N18,933 and 18,469; article 10 item a)
of the supreme decree N1,222 of year 1996, by the Health Care Ministry, approving
the Regulations of the Public Health Institute of Chile; as well as the resolution
N1,600 of year 2008 by the Comptroller General of the Republic; and the supreme
decree N122 dated December 28th 2010 by the same bureau, I issue the following:
Resolution:
One. Be it approved the following Reference Manual for Sanitary Registration
of Orphan Drugs in the Public Health Institute of Chile, which shall be applied by all
employees of the National Drugs Department:
1.- Basic glossary for the purposes of this resolution:
a)
b)
c)

Infrequent, minority, rare or orphan disease: Life-threatening

disease or disability over 2/3 parts of the body, having a low prevalence of
5 cases per 10,000 people.
Orphan pharmaceutical product or orphan drug: Medicament
intended for diagnosis, prevention or treatment of an infrequent disease,
timely declared as such.
Sponsor, applicant or claimant party: Natural or legal person
accrediting the invention or development of an orphan medical product or
orphan drug, requesting for themselves or for third parties the declaration
as such and the subsequent granting of exclusive commercial rights under
the terms and conditions established by the law.

2.- Requirements for the sanitary registration of orphan pharmaceutical

products:
a)

b)

c)

d)

The Public Health Institute of Chile, by means of the National Drugs

Department, will resolve these applications in a reduced term, applying
the urgency procedure as established by article 63rd of Law
N19,880/2003, especially if the pharmaceutical product was approved
by the U.S. Food and Drug Administration (FDA) or the E.U. European
Medicines Agency (EMA). This will be applicable with the proviso that,
upon filing the application, the claimant party duly fulfils the stipulations
established in the regulations currently in force with regard to sanitary
registrations or as required by the present resolution.
In the examination it will be accepted the absence of phase III clinical
trials, carried out with a great casuistry, which must be completely
justified by the interested party. In order to complement the clinical
information of the product, the last reports of adverse events maintained
by the applicant in their registers on the international level must be
submitted, if applicable (PSUR: Periodic Safety Update Reports).
Upon filing the registration application, the interested party shall duly
demonstrate that it is an orphan drug by means of certificates issued by
sanitary authorities, such as the FDA or EMA, accrediting the condition of
orphan drug for the reference medicament, or that the medicament is
included in lists of orphan drugs prepared by the Health Care Ministry for
such purposes.
In the examination of the efficacy period, stability tests shall be accepted
by enclosing the respective design of development batches or pilot
batches or industrial batches. At least one batch (either a development or
pilot or industrial batch) from each manufacture step shall be accepted,
allowing a provisional efficacy period of no more than 24 months to be
obtained, as pertinent in view of the provided data. Then, data shall be
completed in accordance with the law currently in force validating this
period as definitive.
i.
ii.

iii.

iv.

The efficacy period shall be validated or extended with pilot

batches or industrial batches evaluated during the manufacture
step and in accordance with the law currently in force.
If only data from development batches is available, results
obtained to the date of the pilot batches or industrial batches
subjected to stability tests must be submitted in a term under 4
years, as established by the sanitary law currently in force.
Likewise, if the application for efficacy period was furnished only
with development batches or pilot batches or industrial batches
which are incomplete or unfinished for validating the assigned
period, a definitive design shall be submitted in a term under 4
years along with the results obtained to the date of the pilot
batches or industrial batches subjected to stability tests, as
established by the sanitary law currently in force.
In order to validate the efficacy period assigned to products
having stability tests of finished development batches or pilot
batches, but without completing the test until the assigned
efficacy period, they shall incorporate at least one industrial batch

v.
vi.
vii.

into the stability chamber, which must remain therein the

pertinent time in accordance with the assigned period.
In the case of products having 3 or more presentations (either
dose or content), the proposal for matrixing designs or bracketing
designs shall be accepted.
In order to extend the efficacy period, the exempt resolution
N1,773/06 and the supreme decree N 3/2010 regarding this
matter, by the Health Care Ministry, must be observed.
Applications for modifying the orphan drugs registry, already
approved by the Institute, shall be resolved in a term under 2
months, with the proviso that upon filing the application the
claimant party fulfills the regulations currently in force.

3.- The Sanitary Authority shall promptly resolve applications for exemption
of series control and quality control of orphan drugs in accordance with articles 187th
and 188th under the supreme decree N 3/2010 by the Health Care Ministry, in a
term under 20 working days, except that due to founded technical reasons said term
could be extended.
4.- Holders of sanitary registrations of orphan products, upon obtaining their
sanitary registration, shall implement an intensive and systematic pharmacovigilance
which must be approved by the Pharmacovigilance Assistant Department of the
National Drugs Department, periodically reporting to said bureau the adverse
reactions which might occur during the procedures.
Two. The Internal Audit Unit of the Institute shall be in charge of monitoring
the compliance of this Procedure, as well as the pertinent legal rules, without
prejudice of the powers and functions granted by the legal system to the Comptroller
General of the Republic.
Be it entered in the record, served on the parties and published in the Official
Gazette.- Mara Teresa Valenzuela Bravo, Head of the Public Health Institute of Chile.