The Collegiate Board of Directors of
the Brazilian Sanitary Surveillance Agency, in the use of the
attribution vested in it by article 11, clause IV, of the Regulation
of ANVISA approved by Decree n. 3.029, of April
16, 1999, c/c article 111, clause I, item " b ", paragraph
1 of the Bylaws approved by Administrative Order n. 593, of August 25, 2000, published in the Federal Employee Gazette of December
22, 2000, in meeting held on May 5, 2003,
whereas Law n. 6.360, of September 23, 1976;
whereas Decree n. 79.094, of January
5, 1977;
whereas Law n. 9.787, of February
10, 1999;
whereas Decree n. 3.181, of September
23, 1999;
whereas Resolution n. 41, of April of 28, 2000;
whereas the Technical Regulation approved
by Resolution RDC n. 84, of March 19, 2002 and the Handbook
of Good Practices in Bioavailability/Bioequivalence;
whereas the need to regulate the procedures to be followed by the national
and international Centers interested in carrying out Bioavailability/Bioequivalence
assays for the purpose of medicine registration;
whereas the necessity to verify “in Ioco” the proceedings technician,
operational, scientific and ethical adopted in the accomplishment
of the studies of Bioavailability/Bioequivalence for medicines;
whereas the need to standardize the actions of the National Sanitary Surveillance
System;
has adopted the following Resolution
of the Collegiate Board of Directors and I, Director-Chairman,
deputy, determine its publication:
TITLE I
GENERAL CONSIDERATIONS
Article 1. The Centers that carry out Bioavailability/Bioequivalence studies
for the purpose of medicine registration shall observe the rules
and technical regulations in force.
Article 2. For the purposes of this RDC, the following definitions shall
be adopted:
Center of Bioavailability/Bioequivalence of Medicines: research institution which
carries out at least one of the three phases that comprise the
study in question - Clinical, Analytical and Statistical –becoming
responsible, technically and legally, for the authenticity of
the data and information of the entire process, in the terms
of this Resolution.
Responsible for the Phase: natural
person qualified by his or her professional education, training
and experience, responsible for the correct execution and/or
coordination of the study phase assigned to him or her.
Coordinator of the Center: natural
person responsible for the administrative coordination of the
phases under the competence of the Center.
Main Researcher: natural person
qualified by his or her professional education, training and
experience, responsible for the technical-scientific coordination
of the Bioavailability/Bioequivalence study and for the preparation
of its final report of exactly, in the terms of the current
legislation.
TITLE II
CERTIFICATION OF GOOD PRACTICES
IN BIOAVAILABILITY/BIOEQUIVALENCE OF MEDICINES
Article 3. The Bioavailability/Bioequivalence studies carried
out in the country and abroad shall only be accepted, for the
purpose of medicine registration, when carried out by Centers
that are properly Certified by the Brazilian Sanitary Surveillance
Agency.
Article 4. In order to apply for
the Certification of
Good Practices in Bioavailability/Bioequivalence, the interested
part shall fill out the Application Form, according to
Annex I, available at: http://www.anvisa.gov.br.
Paragraph 1. The form shall be filled out and instructed by the documents
requested, and later forwarded to the headquarters of the Brazilian
Sanitary Surveillance Agency/General Office of
Inspection and Control of Medicines and Products.
Paragraph 2. The Center of Bioavailability/Bioequivalence
is solely responsible for filling out and sending
the Application Form containing the information regarding
the activities carried out by the Center.
Paragraph 3. The Sanitary Surveillance Inspection Fee is provided for in
Resolution - RDC n. 23, of
February 6, 2003.
Paragraph 4. After evaluation of
the Application Form and other documents for the Certification,
the General Office of Inspection and Control of Medicines and
Products shall schedule inspection at the unit(s). For the purposes
of inspection, the items set forth in the
Guidelines for Inspection at Centers of Bioavailability/Bioequivalence
of Medicines, according
to Annex II
Article 5. The Certification referred to in the previous article, issued according to Annex III, shall depend on proof of compliance with the
national and international standards for Clinical Research,
the technical regulations in force pertaining to assays of Bioavailability/Bioequivalence
of medicines and the Guidelines for Inspection of Good Practices
in Bioavailability / Bioequivalence by the requesting Center.
TITLE III
OUTSOURCING/LEASING
Article 6. In order to outsource, the contracting Center shall forward
to GGIMP/ANVISA the Form
for Outsourcing, according to Annex IV
Paragraph1. The Form for Outsourcing
shall include the activities that are to be carried out by the contracting Center and the contracted
Center, including knowledge of the terms of the operation by
the sponsoring industry.
Paragraph 2. Outsourcing may only
be done with Centers duly certified by
ANVISA. The phase
outsourcing contract shall be filed at the Center
responsible for the study.
Paragraph 3. The outsourcing contract does not exempt the contractor from
its technical and legal responsibilities regarding the procedures
adopted and the results
obtained.
Paragraph 4. The phase outsourcing
contract shall be carried out by research protocol or by set of protocols.
Paragraph 5. The sub-contracting of the outsourced phase is prohibited.
Paragraph 6. For the purpose of
outsourcing of phase, the contracted Center shall keep
record of the documentation generated during the execution of
the contracted phase and the Center responsible for the study
shall keep record of the full documentation of the phases of
the study.
Article 7. The Centers of Bioavailability/Bioequivalence that carry out
the Clinical Phase shall make available an appropriate
place for confinement
of subjects. The place
may belong to the Center or be leased, and at least one physician
from the Center or clinical staff of the leased unit must be
present while the activities are carried out.
Paragraph 1. In the cases of leasing,
the contracts may only be entered into with units that have
and provide proof of adequate operational and technical capacity, subject to inspection by ANVISA.
Paragraph 2. The hospitalization
unit must have a sufficient
number of beds, in such a way as to contemplate the correct
execution of the studies, in a place that ensures the privacy
and health of the subjects.
Article 8. In carrying out the
Clinical Phase of the Bioavailability
/ Bioequivalence assays, the clinical analyses laboratory tests
shall be carried out in laboratories that possess valid Sanitary
License, issued by the competent sanitary authority.
They might also be evaluated by the technical body of
ANVISA, regarding the standards of Good Practices of
Clinical Laboratory.
Only paragraph. In the cases of
the laboratories evaluated, the result of the evaluation will
be considered with a view to
registration of those that shall
carry out the clinical analyses tests of the phase.
TITLE IV
TRANSITORY AND FINAL DISPOSALS
Article 9. The legal effects referring to the
approval of the Centers shall only hold after the publication
of the Certification in the Federal Employee Gazette. ANVISA shall provide the
updated list of Certifications on its website.
Article 10. The certified Centers shall be monitored through
regular inspection or at any time, in cases of charge or quality deviation.
Article 11. All the documentation pertaining to the Bioavailability/Bioequivalence assays shall
remain filed and available
for at least 15 (fifteen) years, as from the date of conclusion
of the study.
Article 12. The national Centers shall forward to GGIMP/ANVISA/MS,
obligatorily, Monthly Report of Assay of Bioavailability/Bioequivalence
of Medicines, according to Annex V available at: http//www.anvisa.gov.br.
Article 13. The national and international
Centers previously qualified, according to the list available
at the website of ANVISA, are granted 120 (one hundred and twenty)
days, as from the date of publication of this RDC, to adapt
to the conditions set forth hereby, and shall apply for the
Certification of Good Practices in Bioavailability/Bioequivalence
of Medicines.
Only paragraph. After the abovementioned
period of time, only the
Bioavailability/Bioequivalence studies, for the purpose of medicine
registration, carried out by duly
certified entities shall be accepted, with respective
publication in the Federal Employee Gazette.
Article 14. Failure to comply with
the provisions set forth in this Resolution, including evidence
of errors in the execution of the activities under the responsibility
of the Center, as well as other cases not provided for by this rule, shall be evaluated by the General Office of Inspection and Control of
Medicines and Products/ANVISA.
Article 15. Articles
1, 2, 3, 5, 6, Annex I – item 3.a and Statistical Phase
– item 2 and Annex II of Resolution n. 41, of
April 28, 2000, are hereby revoked:
Article 16. This Resolution enters into force on the date of its publication.
CLAUDIO MAIEROVITCH PESSANHA ENRIQUES
Annex I – Application
Form for Certification of Good Practices in Bioavailability/
Bioequivalence of Medicines.
(in
word)
(in
english)
Annex II –
Guidelines for Inspection at Centers of
Bioavailability/Bioequivalence of
Medicines. (in word) (in
portuguese)
Annex III – Certificate
of Good Practices of Bioavailability/Bioequivalence of Medicines.
(GIF
format)
(in
portuguese)
Annex IV – Form
for Outsourcing of Phase for Assays of Bioavailability/Bioequivalence
of Medicines. (in word) (in
portuguese)
Annex V – Form for
Monthly Report of Assays of Bioavailability/Bioequivalence of Medicines. (in word) (in
portuguese)
CLASSIFICATION OF ITEMS OF THE INSPECTION GUIDELINES
The
criteria established for classification is based on the inherent
potential risk to each item in relation to the quality and safety
of the tests and safety of the worker in his interaction with
activities carried out, guaranteeing, in this manner, the reliability
of results obtained.
I. INDISPENSABLE (I): An INDISPENSIBLE
item is one that meets the recommendations of Good Practices
of Bioavailability/Bioequivalence of Medicines, that can influence
on a critical level the quality or safety of assays and
the safety of workers in their interaction with products
and processes during the studies. Define by YES or NO.
II. NECESSARY (N): A NECESSARY item is one that meets the recommendations
of Good Practices of Bioavailability/Bioequivalence of Medicines,
that can influence on a less critical level the quality or safety
of assays and the safety
of workers in their interaction with products and processes
during the studies. Define by YES or NO.
Note: A NECESSARY item not met upon inspection, shall hence be classified
as INDISPENSABLE in the next inspections.
III. RECOMENDABLE
(R): A RECOMMENDABLE item is one that meets the recommendations
of Good Practices of Bioavailability/Bioequivalence of Medicines,
that can influence on a not so critical level the quality or
safety of assays and the safety of workers in their interaction
with products and processes during the studies. Define by YES
or NO.
Note: A RECOMENDABLE item not met upon inspection, shall hence be classified
as NECESSARY in the next inspections. However, it shall never
be treated as INDISPENSIBLE.
IV. INFORMATIVE (INF): An INFORMATIVE
item is one that provides
descriptive information that does not affect the quality or
safety of assays and the safety of workers in their interaction
with products and processes during the realization of studies.
It can be optionally answered by YES or NO, or in a descriptive
manner.
INSPECTION GUIDELINES
1. GENERAL INFORMATION OF THE CENTER
|
N0
|
Qualification
|
Items
|
|
1.1
|
INF
|
Corporate name:
|
|
1.2
|
INF
|
Denomination:
|
|
1.3
|
INF
|
CNPJ:
|
|
1.4
|
INF
|
Legal representative:
|
|
1.5
|
INF
|
Number of Certificate:
|
|
1.6
|
INF
|
Address of the administrative office:
District:
|
|
Municipality:
FU:
ZIP:
Telephone:
Fax:
E-mail:
|
|
1.7
|
INF
|
Address of the operational unit:
Municipality:
|
|
District:
FU:
ZIP:
Telephone: Fax:
E-mail:
|
|
1.8
|
INF
|
Coordinator of the
Center:
|
|
1.9
|
INF
|
Coordinator of the Clinical
Phase:
|
|
1.10
|
INF
|
Coordinator of the Analytical
Phase:
|
|
1.11
|
INF
|
Coordinator of the Statistical
Phase:
|
|
1.12
|
INF
|
Quality manager:
|
|
1.13
|
INF
|
Certified Phase(s):
|
|
1.14
|
INF
|
Outsourced Phase(s) and contracted center(s):
|
|
1.15
|
I
|
Are the outsourced contracts filed appropriately and made available for
inspection?
|
|
1.16
|
I
|
Are the outsourced contracts signed by entities certified by ANVISA?
|
|
1.17
|
INF
|
Operational capacity (Assays/month):
|
|
1.18
|
INF
|
Beginning of operation:
|
|
1.19
|
INF
|
Number of studies carried out until present:
|
2.
INSPECTION DATA
|
N0
|
Qual.
|
Items
|
|
2.1
|
INF
|
Inspection
period:
|
|
2.2
|
INF
|
Reason for
inspection:
|
|
2.3
|
INF
|
Date of the
last inspection:
|
|
2.4
|
INF
|
Reason for
the last inspection:
|
|
2.5
|
INF
|
Persons contacted:
|
|
2.6
|
INF
|
Team of inspectors:
|
3. CLINICAL UNIT
|
3.1. GENERAL INFORMATION
|
|
N°
|
Qual
|
Items
|
|
3.1.1
|
INF
|
Corporate Name:
|
CNPJ:
|
|
3.1.2
|
INF
|
Denomination:
|
|
3.1.3
|
INF
|
Street/Avenue:
District: ZIP:
Municipality:
FU:
|
|
E-mail:
Telephone:
Fax:
E-mail:
|
|
3.1.4
|
INF
|
Legal Representative:
|
|
3.1.5
|
INF
|
Coordinator of the Clinical Phase:
|
|
3.1.6
|
INF
|
Sanitary license issued by the local competent body:
|
|
3.1.7
|
INF
|
Does the company have premises security license issued by the Fire Department?
|
|
3.1.8
|
INF
|
Is there more than one clinical unit for studies?
|
|
3.1.9
|
INF
|
Does the clinical unit have a Hospital Infection Control Commission?
|
|
3.1.10
|
INF
|
Number of beds available for studies:
|
|
3.2 TECHNICAL BODY
|
|
3.2.1
|
INF
|
Number of employees
|
|
|
3.2.2
|
INF
|
Physician
|
|
|
3.2.3
|
INF
|
Pharmacist
|
|
|
3.2.4
|
INF
|
Nutritionist
|
|
|
3.2.5
|
INF
|
Biologist
|
|
|
3.2.6
|
INF
|
Bio-medico
|
|
|
3.2.7
|
INF
|
Nurse
|
|
|
3.2.8
|
INF
|
Nursing assistant
|
|
|
3.2.9
|
INF
|
Laboratory
Technicians
|
|
|
3.2.10
|
INF
|
Others
|
|
|
3.3. PREMISES
General Conditions
|
|
N°
|
Qual
|
Items
|
|
3.3.1
|
INF
|
What is the
physical area of the hospitalization wing?
|
|
3.3.2
|
INF
|
Are there sources of environmental pollution and contamination
close to the clinical unit?
|
|
3.3.3
|
N
|
Are the vicinities of the buildings clean?
|
|
3.3.4
|
R
|
Do the external aspects of building(s)
show good conservation (free from cracks, infiltration,
etc.)?
|
|
3.3.5
|
N
|
Are the floors, walls and roofs suitable for the activities developed
in the area?
|
|
3.3.6
|
N
|
Are the premises built in such a manner so as to allow protection against
the entry of insects and other animals?
|
|
3.3.7
|
R
|
Is the lighting appropriate?
|
|
3.4. ADDITIONAL INSTALATIONS
|
|
N°
|
Qual
|
Items
|
|
3.4.1
|
R
|
Is there a sufficient number of changing rooms for employees (related
to the area and the number of employees)?
|
|
‘3.4.2
|
N
|
Are they
in appropriate hygienic conditions?
|
|
3.4.3
|
R
|
Are there
toilets in sufficient number for the employees (related
to the area and the number of employees)?
|
|
3.4.4
|
N
|
Are they
in appropriate hygienic conditions?
|
|
3.4.5
|
R
|
Is the access
to the employees’ toilets separate from the hospitalization areas?
|
|
3.4.6
|
N
|
Are there electric power generators for emergency cases?
|
|
3.5. HOSPITALIZATION WING
|
|
N°
|
Qual
|
Items
|
|
3.5.1
|
I
|
Is the area
exclusive for subjects during hospitalization periods?
|
|
3.5.2
|
N
|
Is the lighting
appropriate in the hospitalization wing?
|
|
3.5.3
|
N
|
Is ventilation
appropriate in the hospitalization wing?
|
|
3.5.4
|
INF
|
How is the
distribution of beds, in a ward with various beds or in
apartments?
|
|
3.5.5
|
INF
|
What furniture
and equipment is available in the bed areas?
|
|
3.5.6
|
N
|
Are there
sufficient toilets?
|
|
3.5.7
|
N
|
Are the toilets
in hygienic conditions and are they provided with hot
and/or cold water, soap, and towels or driers?
|
|
3.5.8
|
N
|
Is there
a nursing center?
|
|
3.5.9
|
INF
|
What is the
area of the ward?
|
|
3.5.10
|
R
|
Is there
a room for the nursing team to rest?
|
|
3.5.11
|
I
|
Is there
a physician on duty at the place of the study during the
entire period of hospitalization?
|
|
3.5.12
|
R
|
Is there
a room for the physician to rest?
|
|
3.5.13
|
N
|
Is there
an office for assessment of subjects?
|
|
3.5.14
|
I
|
Does the clinical unit have an intensive care unit
(ICU)?
|
|
3.5.15
|
INF
|
Is the ICU movable or is it part of the clinical unit?
|
|
3.5.16
|
I
|
In case of movable ICU, will it be available at the place of hospitalization in the period
of greater risk of occurrence of serious adverse effects?
|
|
3.5.17
|
I
|
In case of movable ICU, is there a previously agreed
fixed unit for transfer of the subject?
|
|
3.5.18
|
INF
|
What is the distance between the hospitalization wing and the ICU?
|
|
3.5.19
|
INF
|
Is there
a refectory?
|
|
3.5.20
|
N
|
Is there
a leisure area reserved for subjects?
|
|
3.5.21
|
INF
|
What furniture
and equipment are available in the leisure area?
|
|
3.6. EQUIPMENT
|
|
N°
|
Qual
|
Items
|
|
3.6.1
|
R
|
Is the distribution of equipment/instruments arranged rationally?
|
|
3.6.2
|
R
|
Does the emergency equipment have a no-break power system?
|
|
3.7. CONSULTING/NURSING OFFICE
|
|
3.7.1
|
I
|
Is there a sphygmomanometer? Conditions?
|
|
3.7.2
|
N
|
Are they calibrated periodically? What type
of calibration?
|
|
3.7.3
|
I
|
Is there
a stethoscope? Conditions?
|
|
3.7.4
|
I
|
Are there
thermometers? Conditions/
|
|
3.8. EMERGENCY TROLLEY
|
|
3.8.1
|
I
|
Is there
an oxygen mask?
|
|
3.8.2
|
I
|
Is there
an Ambu?
|
|
3.8.3
|
I
|
Is there
a Laryngoscope?
|
|
3.8.4
|
I
|
Is there
an intubation tube with cuff in good conditions?
|
|
3.8.5
|
I
|
Are there
disposable syringes?
|
|
3.8.6
|
I
|
Are there
emergency medicines? Which ones?
|
|
3.9. ROOM FOR
PREPARATION OF SAMPLES
|
|
3.9.1
|
INF
|
Are the samples
prepared in the clinical unit or sent to another unit?
|
|
3.9.2
|
R
|
Is there
a room reserved for preparation of samples?
|
|
3.9.3
|
N
|
Is there
a centrifuge? Is it refrigerated? Is it calibrated?
|
|
3.9.4
|
N
|
Is there
a procedure for cleaning and decontamination of the centrifuge?
|
|
3.9.5
|
R
|
Is there
a freezer?
|
|
3.9.6
|
N
|
Is there
temperature of the freezers recorded Are the thermometers
used calibrated by a laboratory accredited by RBC (Brazilian
Network of Calibration)?
|
|
3.9.7
|
R
|
Is there
a refrigerator?
|
|
3.9.8
|
N
|
Is there
temperature of the refrigerators recorded?
|
|
3.10.
DOCUMENTATION
|
|
N°
|
Qual
|
Items
|
|
3.10.1
|
N
|
Is there
a clinical record of the study considering its particularities?
|
|
3.10.2
|
N
|
Do the clinical
records of subjects contain all necessary data (name,
age, sex, address, etc)?
|
|
3.10.3
|
I
|
Is personal
data of volunteers handled within medical secrecy?
|
|
3.10.4
|
INF
|
Is the data
entry system computerized or manual in the form of a protocol
register?
|
|
3.10.5
|
N
|
Is there
a record book for verification of dispensed medicines?
|
|
3.10.6
|
I
|
Are the medical
records of subjects maintained for a minimum period of
five years?
|
|
3.10.7
|
R
|
Is there
a databank of subjects?
|
|
3.11. GOOD CLINICAL PRACTICES
|
|
3.11.1
|
I
|
Are the study
protocols and amendments submitted to the Committee for
Ethics in Research?
|
|
3.11.2
|
I
|
Are all protocols
approved by the CER before being initiated?
|
|
3.11.3
|
I
|
Are the studies
carried out in compliance with the protocol previously
approved by the CER?
|
|
3.11.4
|
INF
|
Does the
institution have a CER ?
|
|
3.11.5
|
INF
|
Is the researcher
or any member of the research team a member of the CER?
If yes, is he or she refrained from judgment of his or
her own research?
|
|
3.11.6
|
I
|
Is the Research Ethics Committee registered in the CONEP?
|
|
3.11.7
|
I
|
Is the Term of Free and Informed Consent dated and signed before any clinical procedure?
|
|
3.11.8
|
INF
|
Who is responsible
for the process of obtaining the Term of Free and Informed
Consent?
|
|
3.11.9
|
N
|
Are the studies
carried out in accordance with national and international
standards (ICH/GCP)?
|
|
3.11.10
|
N
|
Is all the
information generated in the course of clinical study registered and stored in order to guarantee
a precise report?
|
|
3.11.11
|
N
|
Is there
a specific field for registration of adverse effects in
clinical records?
|
|
3.11.12
|
N
|
Are the adverse
effects notified to the CER and ANVISA?
|
|
3.11.13
|
I
|
Is the confidentiality of the subjects’ records properly maintained?
|
|
3.11.14
|
N
|
Are the research
medicines stocked
in appropriate place, with temperature and humidity control?
|
|
3.11.15
|
N
|
Are the research
medicines dispensed in accordance with the study standards?
|
|
3.11.16
|
N
|
Is there insurance for the subjects?
|
|
3.11.17
|
N
|
Is there
compensation for subjects that participate in studies?
|
|
3.11.18
|
R
|
Is there
a procedure for monitoring of the study by the sponsor?
|
|
3.11.19
|
N
|
Is there
a program for medical referral of subjects in which some
illness in pre-study examinations is detected?
|
|
3.11.20
|
N
|
Is there
a continuous medical treatment agreement in case of after-effects
caused by adverse effects of drugs?
|
|
3.12. TECHNICAL BODY
|
|
3.12.1
|
N
|
Does the
main researcher have experience in the conduction of clinical
studies?
|
|
3.12.2
|
N
|
Does the
team rely on the support of a medical body?
|
|
3.12.3
|
N
|
Does the
team rely on the support of a nursing team?
|
|
3.12.4
|
N
|
Is there
a program of qualification and training of employees?
|
|
3.12.5
|
N
|
Are there
records referring to the qualification and training of
employees?
|
|
3.12.6
|
N
|
Does the
team have uniforms?
|
|
3.12.7
|
N
|
Are the uniforms
clean and in good
condition?
|
|
3.12.8
|
N
|
Is the number
of persons responsible for collection sufficient for the
number of subjects hospitalized in each period?
|
|
3.12.9
|
R
|
In case of hospitalization of subjects carried out
in non-hospital unit, is the physician supervising the
study qualified in emergency care?
|
|
3.13. PROCEURES
|
|
3.13.1
|
INF
|
What are
the tests taken by the subjects?
|
|
3.13.2
|
INF
|
What is the
validity period of testes taken by the subjects?
|
|
3.13.3
|
N
|
Upon inclusion of subject in the study, is
the validity period of the tests (maximum 3 months) respected?
|
|
3.13.4
|
INF
|
What is the
procedure for hospitalization of subjects?
|
|
3.13.5
|
INF
|
Who receives
the subjects at the place of hospitalization?
|
|
3.13.6
|
R
|
Upon hospitalization, is an inventory carried out of the subjects’ belongings,
in order to make sure they are not bringing, food, medicines
and others?
|
|
3.13.7
|
R
|
Do the subjects receive a kit containing uniform and
personal hygiene items for use during hospitalization?
|
|
3.13.8
|
R
|
Is there
pre-consulting immediately before hospitalization of subjects?
|
|
3.13.9
|
N
|
Are the subjects
hospitalized the day before intake of the medicine?
|
|
3.13.10
|
INF
|
Who is the
person in-charge of receiving, protecting and storing
the study medicines?
|
|
3.13.11
|
N
|
Is the procedure
of preparation and cleaning of beds for hospitalization
adequate?
|
|
3.13.12
|
INF
|
Who watches
over the intake/administration of medicines by subjects?
|
|
3.13.13
|
I
|
Is the first
blood sample taken before intake of the medicine?
|
|
3.13.14
|
I
|
Is the schedule
for blood collection respected rigorously in accordance
with that established in the protocol?
|
|
3.13.15
|
INF
|
What type
of material is used in collection (tubes, syringes, scalpels,
etc)?
|
|
3.13.16
|
N
|
Is there
temperature and arterial pressure control of subjects
during the period of hospitalization?
|
|
3.13.17
|
I
|
Is the menu prepared by a nutritionist
in accordance with the specifications of each study?
|
|
3.13.18
|
INF
|
What is the procedure established for meals of subjects?
|
|
3.13.19
|
I
|
Are post-study
laboratory and clinical tests carried out in subjects?
|
|
3.13.20
|
N
|
Is there
a complications register for the period of hospitalization
of subjects?
|
|
3.13.21
|
INF
|
In case of
adverse events, what procedures are adopted?
|
|
3.13.22
|
INF
|
What is the
discharge procedure of the volunteer?
|
|
3.14. STANDARD OPERATIONAL PROCEDURES
|
|
3.14.1
|
N
|
Is there
SOP for recruitment and selection of subjects?
|
|
3.14.2
|
N
|
Is there
SOP for collection of samples during hospitalization?
|
|
3.14.3
|
N
|
Is there
SOP for identification and preparation of samples?
|
|
3.14.4
|
N
|
Is there
SOP for storage and transport of samples?
|
|
3.14.5
|
N
|
Is there
SOP for hospitalization of subjects?
|
|
3.14.6
|
N
|
Is there
SOP for emergency care of subjects?
|
|
3.14.7
|
N
|
Is there
SOP for cleanliness and preparation of areas for hospitalization
of subjects?
|
|
3.14.8
|
N
|
Is there
SOP for disposal of biological and non-biological materials?
|
|
3.14.9
|
N
|
Is there SOP for receiving and control of medicines under study?
|
4. CLINICAL ANALYSES LABORATORY
|
4.1 GENERAL INFORMATION
|
|
N°
|
Qual
|
Items
|
|
4.1.1
|
INF
|
Corporate Name:
|
CNPJ:
|
|
4.1.2
|
INF
|
Denomination:
|
|
4.1.3
|
INF
|
Street/Avenue:
District:
ZIP:
|
|
Municipality: FU:
Telephone:
Fax:
E-mail:
|
|
4.1.4
|
INF
|
Legal Representative:
|
|
4.1.5
|
INF
|
Technical Coordinator:
|
|
4.1.6
|
INF
|
Quality Manager:
|
|
4.1.7
|
INF
|
Sanitary License issued by local competent body:
|
|
4.1.8
|
INF
|
Does the company have premises security license issued by the Fire Department?
|
|
4.1.9
|
INF
|
Does the
company have the authorization from the environmental
protection body? Which one?
|
|
4.1.10
|
INF
|
Tests carried
out for Bioequivalence studies:
|
|
4.1.11
|
INF
|
Outsourced
tests and outsourced parties:
|
|
4.1.12
|
INF
|
Number of
tests/month:
|
|
4.2. TECHNICAL BODY
|
|
4.2.1
|
INF
|
Number of
employees
|
|
|
4.2.2
|
INF
|
Physician
|
|
|
4.2.3
|
INF
|
Pharmacist
|
|
|
4.2.4
|
INF
|
Biologist
|
|
|
4.2.5
|
INF
|
Bio-medic
|
|
|
4.2.6
|
INF
|
Chemist
|
|
|
4.2.7
|
INF
|
Nurse
|
|
|
4.2.8
|
INF
|
Technicians
|
|
|
4.2.9
|
INF
|
Others
|
|
|
4.3. INSTALLATIONS
General Conditions
|
|
N°
|
Qual
|
Items
|
|
4.3.1
|
INF
|
Are there sources of environmental pollution and contamination
close to the clinical unit?
|
|
4.3.2
|
INF
|
Are the vicinities of the buildings clean?
|
|
4.3.3
|
N
|
Do the external aspects of building(s)
show good conservation (free from cracks, infiltration,
etc.)?
|
|
4.3.4
|
N
|
Are the floors, walls and roofs suitable for the activities developed
in the area?
|
|
4.3.5
|
N
|
Are the premises built in such a manner so as to allow protection against
the entry of insects and other animals?
|
|
4.3.6
|
N
|
Is the lighting appropriate?
|
|
4.4. ADDITIONAL INSTALLATIONS
|
|
N°
|
Qual
|
Items
|
|
4.4.1
|
R
|
Is there a sufficient number of changing rooms for employees (related
to the area and the number of employees)?
|
|
4.4.2
|
N
|
Are they in appropriate hygienic conditions?
|
|
4.4.3
|
R
|
Are there
toilets in sufficient number for the employees (related
to the area and the number of employees)?
|
|
4.4.4
|
N
|
Are they
in appropriate hygienic conditions?
|
|
4.4.5
|
N
|
Is the access
to the employees’ toilets separate from the technical areas of the laboratory?
|
|
4.5. DOCUMENTATION OF SUBJECTS
|
|
N°
|
Qual
|
Items
|
|
4.5.1
|
N
|
Do the clinical
records of subjects contain all necessary data (name,
age, sex, address, etc)?
|
|
4.5.2
|
INF
|
Are samples
identified by codes?
|
|
4.5.3
|
INF
|
Is there
a different treatment of tests done by subjects? (No.
of the study protocol, special identification, specific
equipment, etc).
|
|
4.5.4
|
INF
|
Is the data
entry system computerized or manual in the form of a protocol
register?
|
|
4.6.
SAMPLE
|
|
N°
|
Qual
|
Items
|
|
4.6.1
|
INF
|
Where is
the biological material of subjects collected?
|
|
4.6.2
|
R
|
Is the Collection
Room easily accessible?
|
|
4.6.3
|
INF
|
Is the Collection
Room divided into booths?
|
|
4.6.4
|
N
|
Does the
Collection Room have a wash-basin for washing hands?
|
|
4.6.5
|
N
|
Is there
a box for disposal perforating materials?
|
|
4.6.6
|
R
|
Is it air-conditioned?
|
|
4.6.7
|
I
|
Is the collection
room found in ideal clean conditions?
|
|
4.6.8
|
I
|
Is the material
used in collection disposable?
|
|
4.6.9
|
I
|
In the collection
procedure, are the tubes identified adequately in a way
so as to avoid exchange of samples?
|
|
4.6.10
|
R
|
Is collection
done in primary tubes?
|
|
4.7. SELECTION
OF SAMPLES
|
|
N°
|
Qual
|
Items
|
|
4.7.1
|
R
|
Is the Selection
Room independent?
|
|
4.7.2
|
INF
|
Are samples
prepared for internal transport?
|
|
4.7.3
|
N
|
Are samples
prepared for external transport ?
|
|
4.7.4
|
INF
|
How are the
samples sent to sectors in-charge? (with a printed work
protocol, bar code)?
|
|
4.8.
Storage
|
|
N°
|
Qual
|
Items
|
|
4.8.1
|
INF
|
Is the analysis
of these samples carried out immediately after they are
received?
|
|
4.8.2
|
N
|
Are the samples
stored in an adequate place and temperature?
|
|
4.8.3
|
N
|
Is there
temperature control of places of storage?
|
|
4.8.4
|
N
|
Are the containers
used for storage adequate?
|
|
4.8.5
|
INF
|
For how long
are the samples maintained for re-analysis/counter-test?
|
|
4.8.6
|
N
|
Is the procedure for disposal of biological material adequate?
|
|
4.9. EXTERNAL TRANSPORT OF SAMPLES
|
|
N°
|
Qual
|
Items
|
|
4.9.1
|
INF
|
Is there
external transport of biological samples?
|
|
4.9.2
|
INF
|
Are the samples
received processed in their place of origin?
|
|
4.9.3
|
N
|
Are thermal boxes with dry/recyclable ice for external transport of refrigerated
samples?
|
|
4.9.4
|
INF
|
What is the
method used for external transport of biological samples?
|
|
4.9.5
|
INF
|
What is the
average duration of external transport of samples?
|
|
4.10. INTERNAL TRANSPORT OF SAMPLES
|
|
N°
|
Qual
|
Items
|
|
4.10.1
|
INF
|
How is internal transport of samples done?
|
|
4.11. RECORD OF RESULTS OF TESTS
|
|
N°
|
Qual
|
Items
|
|
4.11.1
|
INF
|
Are the results
recorded in the work protocol?
|
|
4.11.2
|
INF
|
Are the results
recorded in protocol books?
|
|
4.11.3
|
INF
|
Are the results
transferred to a computerized system?
|
|
4.11.4
|
R
|
Is there
an equipment interface with the system of registration
of results?
|
|
4.11.5
|
INF
|
If negative, how often are results transcribed until
release of the final report?
|
|
4.11.6
|
N
|
Is there a procedure for checking the transcribed results?
|
|
4.12. TEST REPORT
|
|
N°
|
Qual
|
Items
|
|
4.12.1
|
INF
|
Is the test report printed directly from the computerized system?
|
|
4.12.2
|
N
|
Are there
reference values?
|
|
4.12.3
|
N
|
Are the methodologies
applied specified?
|
|
4.12.4
|
R
|
Is the equipment
used specified?
|
|
4.12.5
|
I
|
Is the report
signed by a professional in-charge?
|
|
4.12.6
|
INF
|
Is the report handed over directly to the subject or to the physician
responsible for the study?
|
|
4.13. TRACKING OF INFORMATION
|
|
N°
|
Qual
|
Items
|
|
4.13.1
|
I
|
Does the laboratory information system allow tracking of results of tests
carried out in subjects?
|
|
4.13.2
|
INF
|
Is there a specific filing system for data on the subjects?
|
|
4.14. COMPUTERIZATION/INTERFACING
|
|
N°
|
Qual
|
Items
|
|
4.14.1
|
INF
|
Are the areas of the laboratory interconnected by means of a network?
|
|
4.14.2
|
R
|
Is the analytical equipment interfaced in order to avoid transcriptions?
|
|
4.15. ORGANIZATION OF THE LABORATORY ENVIRONMENT
|
|
N°
|
Qual
|
Items
|
|
4.15.1
|
R
|
Is the physical
space divided adequately among different sectors of the
laboratory?
|
|
4.15.2
|
R
|
Is the position
of counters in relation to the cabinets and equipment
operational?
|
|
4.15.3
|
R
|
Is the position
of freezers and refrigerators operational?
|
|
4.15.4
|
R
|
Is the means
of access of technicians good?
|
|
4.15.5
|
R
|
Is there
adequate place for keeping glass ware of immediate use?
|
|
4.15.6
|
R
|
Is access
to electric current made easy?
|
|
4.15.7
|
R
|
Is there
a specification of the type of electric current?
|
|
4.15.8
|
N
|
Is the laboratory
environment air-conditioned?
|
|
4.15.9
|
N
|
Is there
ambient temperature control?
|
|
4.16. ORGANIZATION OF THE WORK COUNTER
|
|
N°
|
Qual
|
Items
|
|
4.16.1
|
N
|
Are the counters
sufficient in relation to the construction material?
|
|
4.16.2
|
N
|
Were they
clean at the time of the inspection?
|
|
4.16.3
|
N
|
Are they
cleaned and disinfected before and after use?
|
|
4.16.4
|
R
|
Is protection
used in counters while working?
|
|
4.16.5
|
N
|
Are the SOP’s
accessible to technicians close to the counters?
|
|
4.16.6
|
R
|
Is there support for automatic pipettes?
|
|
4.17. GOOD LABORATORY PRACTICES
|
|
N°
|
Qual
|
Items
|
|
4.17.1
|
N
|
Is there
a Quality Guarantee System, with designated staff to ensure
that the responsibilities are carried out in accordance
with the principles of the existing technical standards
(BPL, ISO, OECD)?
|
|
4.17.2
|
INF
|
Does the
quality manager have other functions in the program of
the laboratory?
|
|
4.17.3
|
N
|
Does the
quality management undertake internal audits?
|
|
4.17.4
|
INF
|
What is the
frequency of internal audits?
|
|
4.17.5
|
N
|
Are there
records of internal audits?
|
|
4.17.6
|
N
|
Is there
a training program for employees of the laboratory?
|
|
4.17.7
|
N
|
Is the staff
trained and guided in such a manner so as to guarantee
correct and full execution of
processes and procedures defined?
|
|
4.17.8
|
I
|
Are there
Standard Operational Procedures?
|
|
4.17.9
|
N
|
Are SOP’s
suitable and used by the different sectors?
|
|
4.17.10
|
N
|
Is there
a Quality Manual?
|
|
4.17.11
|
N
|
Does the
laboratory participate in assay proficiency programs?
|
|
4.17.12
|
R
|
Is it a member
of any technical-scientific
association? Which
associations?
|
|
4.18. STANDARD OPERATIONAL PROCEDURES
|
|
N°
|
Qual
|
Items
|
|
4.18.1
|
N
|
Is there
SOP for use and maintenance of instruments?
|
|
4.18.2
|
N
|
Is there SOP for use and maintenance of equipment?
|
|
4.18.3
|
N
|
Is there
SOP for disinfection of reusable utensils?
|
|
4.18.4
|
N
|
Is there
SOP for washing of glass ware?
|
|
4.18.5
|
N
|
Is there
SOP for cleaning installations?
|
|
4.18.6
|
N
|
Is there
SOP for collecting biological material?
|
|
4.18.7
|
N
|
Is there
SOP for external transport of samples?
|
|
4.18.8
|
N
|
Is there SOP for disinfection and disposal of biological and non-biological
material?
|
|
4.19. EQUIPMENT
|
|
N°
|
Qual
|
Items
|
|
4.19.1
|
N
|
Has the equipment
been installed according to the manufacturer’s specifications?
|
|
4.19.2
|
INF
|
Is the equipment
automatic? What type of calibration?
|
|
4.19.3
|
N
|
Is the equipment
calibrated regularly?
|
|
4.19.4
|
R
|
Is there
a procedure for cleaning and decontaminating the equipment?
|
|
4.19.5
|
R
|
Is there
preventive and corrective maintenance of equipment?
|
|
4.19.6
|
N
|
Is there
a record of calibration of equipment?
|
|
4.19.7
|
N
|
Are the centrifuge(s)
and thermometers certified by INMETRO or an accredited
laboratory (RBC)?
|
|
4.19.8
|
N
|
Is there
a temperature record
of double-boilers?
|
|
4.19.9
|
N
|
Is there
a temperature record for the refrigerators?
|
|
4.19.10
|
N
|
Is there
a temperature record for the freezers?
|
|
4.19.11
|
N
|
Is there
a record for verification of the performance of automatic
pipettes?
|
|
4.19.12
|
I
|
Are the used
ferrules discarded?
|
|
4.19.13
|
N
|
Is there
an electric current stabilizer?
|
|
4.20.
REAGENTES
|
|
N°
|
Qual
|
Items
|
|
4.20.1
|
I
|
Do the reagents
have a lot number and validity date?
|
|
4.20.2
|
I
|
Are the reagents
within the validity period?
|
|
4.20.3
|
N
|
Is the storage
of reagents in the laboratory for immediate use adequate?
|
|
4.20.4
|
N
|
Is the storage of reagents done in ideal conditions
of temperature and humidity?
|
|
4.20.5
|
N
|
Are there temperature and humidity records books of the places of storage?
Are the thermometers certified by INMETRO or accredited laboratory (RBC)?
|
|
4.20.6
|
INF
|
Are there
refrigerators?
|
|
4.20.7
|
INF
|
Are there
freezers?
|
|
4.20.8
|
R
|
Is there
a stock control
book?
|
|
4.20.9
|
INF
|
What is the
system used for obtaining reagent water?
|
|
4.20.10
|
N
|
Does the
laboratory carry out physical-chemical and microbiological
tests for quality control of reagent water?
|
|
4.20.11
|
N
|
Is there
proper labeling of reagent-solutions prepared in the laboratory?
|
|
4.21. BIOSAFETY
Collective Protection
|
|
N°
|
Qual
|
Items
|
|
4.21.1
|
N
|
Is there
a Biosafety Program?
|
|
4.21.2
|
N
|
Is the technical
body of the laboratory submitted periodically to health
examinations?
|
|
4.21.3
|
N
|
Is there
a Vaccination Program of employees?
|
|
4.21.4
|
N
|
Is there
a Waste Treatment Program?
|
|
4.21.5
|
R
|
Is decontamination
of biological waste produced during laboratory activities
carried out?
|
|
4.21.6
|
R
|
Is care taken for conditioning and final disposal of chemical waste?
|
|
4.21.7
|
R
|
Is care taken for conditioning and final disposal of non-contaminated
waste?
|
|
4.21.8
|
I
|
Is there
an emergency shower and eye-wash?
|
|
4.21.9
|
N
|
Are Fire
Extinguishers? Are they within the validity period?
|
|
4.21.10
|
N
|
Is prevention
and notification of accidents done?
|
|
4.21.11
|
N
|
Are adequate
containers used for disposal of broken glass ware and
perforating and cutting material?
|
|
4.21.12
|
R
|
Are there
educative signs warning about risks?
|
|
4.21.13
|
N
|
Is there
information on how to act in case of emergency, such as:
hospital telephone number, proto-help and fire brigade?
|
|
4.21.14
|
R
|
Are first-aid boxes available in case of accidents?
|
|
4.22.
INDIVIDUAL PROTECTION
|
|
N°
|
Qual
|
Items
|
|
4.22.1
|
I
|
Does the
laboratory provide IPE (Individual Protection Equipment)
and train employees to use it?
|
|
4.22.2
|
N
|
Do the employees
use long jackets with long sleeves?
|
|
4.22.3
|
N
|
Do the employees
use disposable gloves?
|
|
4.22.4
|
N
|
Do the employees
use protective goggles or facial protection?
|
|
4.22.5
|
N
|
Do the employees
use masks?
|
|
4.22.6
|
N
|
Do the employees
use closed shoes or protective shoes?
|
|
4.22.7
|
N
|
Do the employees
use clothes that protect the legs (long trousers)?
|
|
4.22.8
|
R
|
Is the laboratory
responsible for washing uniforms used by the employees?
|
|
4.23. STOREROOM
General Conditions
|
|
N°
|
Qual
|
Items
|
|
4.23.1
|
N
|
Is the physical
area appropriate for the amount of material stocked?
|
|
4.23.2
|
N
|
Is the floor, walls and roof suitable for storage of
materials?
|
|
4.23.3
|
N
|
Are they
in good condition?
|
|
4.23.4
|
N
|
Were they
clean at the time of the visit?
|
|
4.23.5
|
R
|
Is there
a program of DDT spraying?
|
|
4.23.6
|
INF
|
Was evidence
of presence of the above-mentioned animals noticed?
|
|
4.23.7
|
R
|
Is the lighting
appropriate?
|
|
4.23.8
|
N
|
Are the temperature
and humidity in accordance with the parameters established
for materials and products stored?
|
|
4.23.9
|
N
|
Is there
temperature and humidity controlling apparatus? Are the
thermometers certified by INMETRO or accredited laboratory
(RBC)?
|
|
4.23.10
|
N
|
Is there
record of temperature
and humidity control?
|
|
4.23.11
|
INF
|
Is there
need for a cold room or refrigerators and freezers?
|
|
4.23.12
|
N
|
Are there
temperature record books for the cold room or for the
refrigerators and freezers?
|
|
4.24. AREAS OF ACTION
|
|
N°
|
Qual
|
Items
|
|
4.24.1
|
INF
|
Are tests
carried out in the area of Biochemistry?
|
|
4.24.2
|
INF
|
Are tests
carried out in the area of Hematology?
|
|
4.24.3
|
INF
|
Are tests
carried out in the area of Immunology?
|
|
4.24.4
|
INF
|
Are tests
carried out in the area of Parasitology?
|
5. ANALITICAL UNIT
|
5.1 ANALYTICAL LABORATORY
General
Information
|
|
N°
|
Qual
|
Items
|
|
5.1.1
|
INF
|
Corporate Name:
|
CNPJ:
|
|
5.1.2
|
INF
|
Denomination:
|
|
5.1.3
|
INF
|
Street/Avenue:
District: ZIP:
Municipality: FU:
E-mail:
|
|
5.1.4
|
INF
|
Is the laboratory composed of more than one unit? (If yes, inform the
address of the other units and specify the attributions
of each unit)
|
|
5.1.5
|
INF
|
Street/Avenue:
District: ZIP:
Municipality: FU:
|
|
E-mail:
Attributions:
|
|
5.1.6
|
INF
|
Legal Representative:
|
|
5.1.7
|
INF
|
Coordinator of the Analytical Phase:
|
|
5.1.8
|
INF
|
Quality Manager:
|
|
5.1.9
|
INF
|
Does the company have premises security license issued by the Fire Department?
|
|
5.1.10
|
INF
|
Does the company have authorization from the environmental protection
body?
|
|
5.2. TECHNICAL BODY
|
|
5.2.1
|
INF
|
Number of
employees
|
|
|
5.2.2
|
INF
|
Physician
|
|
|
5.2.3
|
INF
|
Pharmacist
|
|
|
5.2.4
|
INF
|
Biologist
|
|
|
5.2.5
|
INF
|
Bio-medic
|
|
|
5.2.6
|
INF
|
Chemist
|
|
|
5.2.7
|
INF
INF technicians
|
Technicians
|
|
|
5.2.8
|
INF
|
Others
|
|
|
5.3. INSTALLATIONS
General Conditions
|
|
N°
|
Qual
|
Items
|
|
5.3.1
|
INF
|
What is the
physical area of the laboratory?
|
|
5.3.2
|
INF
|
Are there sources of environmental pollution and contamination
close to the company?
|
|
5.3.4
|
N
|
Are the vicinities of the buildings clean?
|
|
5.3.5
|
N
|
Do the external aspects of building(s)
show good conservation (free from cracks, infiltration,
etc.)?
|
|
5.3.6
|
N
|
Are the premises built in such a manner so as to allow protection against
the entry of insects and other animals?
|
|
5.3.7
|
N
|
Are the floors, walls and roofs suitable for the activities developed
in the area?
|
|
5.3.8
|
INF
|
Is the area exclusive for analysis of biological material?
|
|
5.3.9
|
N
|
Is access restricted to employees?
|
|
5.3.10
|
N
|
Is the lighting appropriate?
|
|
5.3.11
|
N
|
Is the air-conditioning adequate? Is there control
and Record of
temperature and humidity with thermometer certified by
INMETRO or accredited laboratory (RBC)?
|
|
5.4. ADDITIONAL INSTALLATIONS
|
|
N°
|
Qual
|
Items
|
|
5.4.1
|
R
|
Is there a sufficient number of changing rooms for employees (related
to the area and the number of employees)?
|
|
5.4.2
|
N
|
Are they
in appropriate hygienic conditions?
|
|
5.4.3
|
R
|
Are there
toilets in sufficient number for the employees (related
to the area and the number of employees)?
|
|
5.4.4
|
N
|
Are they
in appropriate hygienic conditions?
|
|
5.4.5
|
R
|
Is the access to the employees’ toilets separate from the technical areas
of the laboratory?
|
|
5.4.6
|
INF
|
Are there electric power generators for emergency cases?
|
|
5.5. ORGANIZATION OF THE LABORATORY SPACE
|
|
N°
|
Qual
|
Items
|
|
5.5.1
|
R
|
Is the physical
space distributed adequately for carrying out the laboratory activities?
|
|
5.5.2
|
R
|
Is the position
of counters in relation to the cabinets and equipment
operational?
|
|
5.5.3
|
R
|
Is the position
of freezers and refrigerators operational?
|
|
5.5.4
|
R
|
Is the means
of access of technicians good?
|
|
5.5.5
|
R
|
Is there
adequate place for keeping glass ware of immediate use?
|
|
5.5.6
|
R
|
Is access
to electric current made easy?
|
|
5.6. ORGANIZATION OF THE WORK COUNTER
|
|
N°
|
Qual
|
Items
|
|
5.6.1
|
N
|
Are the counters
sufficient in relation to the construction material?
|
|
5.6.2
|
N
|
Were they
clean at the time of the inspection?
|
|
5.6.3
|
N
|
Are the SOP’s
accessible to technicians?
|
|
5.6.4
|
R
|
Is there support for automatic pipettes?
|
|
5.7. GOOD LABORATORY PRACTICES
|
|
N°
|
Qual
|
Items
|
|
5.7.1
|
N
|
Is there a Quality Guarantee System, with designated staff to ensure
that the responsibilities are carried out in accordance
with the principles of the existing technical standards
(BPL, ISO, OECD)?
|
|
5.7.2
|
N
|
Is the Quality Program available to all the employees?
|
|
5.7.3
|
N
|
Does the laboratory have a quality manager?
|
|
5.7.4
|
INF
|
Does the
quality manager have other functions in the routine of
the laboratory?
|
|
5.7.5
|
N
|
Does the
quality management undertake internal audits?
|
|
5.7.6
|
N
|
Are internal audits undertaken at least once a year?
|
|
5.7.7
|
N
|
Are there records of internal audits?
|
|
5.7.8
|
I
|
Does the coordinator of the analytical phase have qualification
and experience regarding the activities he or she performs?
|
|
5.7.9
|
R
|
Is there a training program for employees of the laboratory?
|
|
5.7.10
|
N
|
Are there records of the training and qualification
of each employee?
|
|
5.7.11
|
N
|
Is the staff trained and guided in such a manner so as to guarantee correct
and full execution of
processes and procedures defined?
|
|
5.7.12
|
N
|
Are new laboratory procedures only implemented after
full evaluation and approval by the Quality Guarantee?
|
|
5.7.13
|
N
|
Does the laboratory
have an organization chart?
|
|
5.7.14
|
I
|
Does it have
Standard Operational Procedures?
|
|
5.7.15
|
N
|
Are the SOP’s
appropriate and are they used by different sectors?
|
|
5.7.16
|
N
|
Does the
Laboratory have records in different sectors?
|
|
5.7.17
|
N
|
Is there
a Quality Manual?
|
|
5.7.18
|
R
|
Is the quality
manual easily accessible to the technical body of the
laboratory?
|
|
5.7.19
|
N
|
Does the
quality manual concern the individual attributions of
the technical and management body?
|
|
5.7.20
|
INF
|
Does it have the certificate of a competent body? Which bodies?
|
|
5.8. STANDARD OPERATIONAL PROCEDURES
|
|
N°
|
Qual
|
Items
|
|
5.8.1
|
N
|
Is there SOP for transporting and receiving samples?
|
|
5.8.2
|
N
|
Is there SOP for storage of samples?
|
|
5.8.3
|
N
|
Is there SOP for identification of samples?
|
|
5.8.4
|
N
|
Is there SOP for washing of glass ware?
|
|
5.8.5
|
N
|
Is there SOP for use, maintenance and validation of chromatographic systems?
|
|
5.8.6
|
N
|
Is there SOP for validation of the analytical method?
|
|
5.8.7
|
N
|
Is there SOP for studies of stability of drugs in biological liquids?
|
|
5.8.8
|
N
|
Is there SOP for the use and maintenance of the pH-meter?
|
|
5.8.9
|
N
|
Is there SOP for use and maintenance of refrigeration systems?
|
|
5.8.10
|
N
|
Is there SOP for use and maintenance of scales?
|
|
5.8.11
|
N
|
Is there SOP for use and maintenance of water systems?
|
|
5.8.12
|
N
|
Is there SOP for the sequence of analytical runs?
|
|
5.8.13
|
N
|
Is there SOP for use and maintenance of pipettes?
|
|
5.8.14
|
N
|
Is there SOP for disinfection and disposal of biological and non-biological
material?
|
|
5.8.15
|
N
|
Is there SOP for assessment of the quality of chromatograms?
|
|
5.8.16
|
N
|
Is there
SOP for establishing the criteria for re-analysis of samples?
|
|
5.8.17
|
N
|
Is there
SOP for the preparation of solutions and standards of
usage?
|
|
5.8.18
|
N
|
Is there SOP for pharmacokinetic analysis of data obtained?
|
|
5.8.19
|
N
|
Is there SOP for storage of the study documentation?
|
|
5.9. EQUIPMENT
|
|
N°
|
Qual
|
Items
|
|
5.9.1
|
INF
|
What equipment is used for analysis of samples?
|
|
5.9.2
|
R
|
Is there a procedure for disinfection of equipment?
|
|
5.9.3
|
R
|
Is the operation manual of each equipment available in the laboratory?
|
|
5.9.4
|
R
|
Is the distribution
of equipment/instruments arranged in a rational manner?
|
|
5.9.5
|
R
|
Is there
an electric current stabilizer?
|
|
5.9.6
|
N
|
Does the
laboratory equipment have a no-break power system?
|
|
5.10. CHROMATOGRAPHIC SYSTEMS
|
|
5.10.1
|
I
|
Is the chromatography equipment Certified/Qualified periodically?
|
|
5.10.2
|
INF
|
How often?
|
|
5.10.3
|
INF
|
What is the
date of the last Certification/Qualification carried out
in the chromatography equipment?
|
|
5.10.4
|
N
|
Is the Certification/Qualification
carried out by qualified company?
|
|
5.10.5
|
N
|
Is there
a preventive and corrective maintenance program for this
equipment?
|
|
5.10.6
|
N
|
Is there
a record for preventive and corrective maintenance?
|
|
5.10.7
|
N
|
Is the chromatographic
equipment adequately installed?
|
|
5.10.8
|
N
|
Are there usage, maintenance and storage procedures of chromatographic
columns?
|
|
5.10.9
|
INF
|
Are the columns used for more than one study?
|
|
5.10.10
|
I
|
Is the ideal temperature range adhered to for operation of the equipment?
|
|
5.11. REFRIGERATION/AIR-CONDITIONING SYSTEMS
|
|
5.11.1
|
INF
|
What is the
temperature specification of the freezers?
|
|
5.11.2
|
N
|
Is there
a temperature record for freezers?
|
|
5.11.3
|
INF
|
Do the freezers
have identification?
|
|
5.11.4
|
N
|
Is the storage
capacity of freezers adhered to?
|
|
5.11.5
|
N
|
Is there
a temperature record for refrigerators?
|
|
5.11.6
|
I
|
Are there alternative procedures in case of an energy shortage in such
a way so as to preserve the content of freezers and refrigerators?
|
|
5.11.7
|
N
|
Are thermometers
installed adequately in the refrigeration systems?
|
|
5.11.8
|
N
|
Is there
a room temperature record?
|
|
5.11.9
|
N
|
Is there
a hygrometer and an ambient humidity record?
|
|
5.11.10
|
R
|
Is there
a procedure for preventive and corrective maintenance
of air-conditioning equipment?
|
|
5.12. WATER SYSTEM
|
|
5.12.1
|
INF
|
What equipment is used for purification of water?
|
|
5.12.2
|
INF
|
Is there a place for storage of purified water?
|
|
5.12.3
|
INF
|
If yes, for how long does the water remain stored?
|
|
5.12.4
|
N
|
Is the water
used submitted
to quality control?
|
|
5.12.5
|
INF
|
How often?
|
|
5.12.6
|
N
|
Is there
a record for quality control of water?
|
|
5.12.7
|
R
|
Is there
a procedure for preventive and corrective maintenance
of water purification equipment?
|
|
5.12.8
|
N
|
Is there
a record for maintenance of the water treatment system?
|
|
5.13. ANALYTICAL SCALE
|
|
5.13.1
|
N
|
Is the scale
certified by INMETRO or accredited laboratory (Brazilian
Calibration Network)?
|
|
5.13.2
|
N
|
Is the analytical
scale installed according to the manufacturer’s recommendations?
|
|
5.13.3
|
N
|
Is there
a standard operational procedure for the use of the analytical
scale?
|
|
5.13.4
|
INF
|
Is there
a procedure for preventive and corrective maintenance
of the analytical scale?
|
|
5.13.5
|
INF
|
Is the calibration
verification procedure carried out daily?
|
|
5.13.6
|
N
|
Is there a record of calibrations carried out?
|
|
5.14. pH METER
|
|
5.14.1
|
I
|
Does the
analytical laboratory have a pH meter?
|
|
5.14.2
|
N
|
Is there
a procedure for the use of the pH meter?
|
|
5.14.3
|
R
|
Is there
a procedure for preventive and corrective maintenance
of the pH meter?
|
|
5.14.4
|
N
|
Is there
a record of calibration of the pH meter?
|
|
5.14.5
|
N
|
Is the pH
meter checked for at least two pH values?
|
|
5.14.6
|
N
|
Are the verification buffers stored according to the manufacturer’s recommendations?
|
|
5.15. CENTRIFUGE
|
|
5.15.1
|
N
|
Is the centrifuge
installed according to the manufacturer’s recommendations?
|
|
5.15.2
|
R
|
Does the
centrifuge have a refrigeration system?
|
|
5.15.3
|
R
|
Is there
a standard operational procedure for use of the centrifuge?
|
|
5.15.4
|
R
|
Is there
a procedure for preventive and corrective maintenance
of the centrifuge?
|
|
5.15.5
|
R
|
Is there
a record for maintenance of the centrifuge?
|
|
5.15.6
|
N
|
Is there a procedure for cleaning and decontamination of the centrifuge?
|
|
5.16. GLASS WARE AND PIPETTES
|
|
5.16.1
|
R
|
Are tests
carried out for verification of the quality of the glass
ware washing process?
|
|
5.16.2
|
R
|
Is the volumetric
glass ware certified by INMETRO or accredited laboratory
(Brazilian Calibration Network)?
|
|
5.16.3
|
R
|
Is the volumetric glass ware kept in an adequate place?
|
|
5.16.4
|
INF
|
What is the
type of material of vials used for the analytical runs?
|
|
5.16.5
|
N
|
Are used
vials discarded?
|
|
5.16.6
|
N
|
Are the automatic
pipettes certified?
|
|
5.16.7
|
R
|
Is there
a procedure for the use of automatic pipettes?
|
|
5.16.8
|
INF
|
Is the frequency of maintenance / calibration of the automatic pipettes
at least annual?
|
|
5.16.9
|
N
|
Is there a record of maintenance/calibration of automatic pipettes?
|
|
5.16.10
|
N
|
Is there
a procedure for cleaning and decontamination of pipettes/micropipettes?
|
|
5.16.11
|
I
|
Are the used
ferrules discarded?
|
|
5.17.
REAGENTS
|
|
N°
|
Qual
|
Items
|
|
5.17.1
|
I
|
Do the reagents
have a lot number and a validity date?
|
|
5.17.2
|
I
|
Are the reagents
within the validity period?
|
|
5.17.3
|
N
|
Is the storage
of reagents done according to manufacturer’s recommendations?
|
|
5.17.4
|
N
|
Does the
laboratory have a temperature and humidity record of the
places of storage?
|
|
5.17.5
|
R
|
Does the
laboratory have stock control books?
|
|
5.17.6
|
R
|
Are the reagents
separated by classes (inflammable, non-inflammable, oxidizing,
acids and bases)?
|
|
5.17.7
|
N
|
Does the
laboratory have an exhaust hood for handling of reagents?
|
|
5.17.8
|
N
|
Is proper
labeling used for solutions-reagents prepared in the laboratory?
|
|
5.18. MOBILE PHASE
|
|
5.18.1
|
INF
|
What degree
of purity of solvents is used for preparation of the mobile
phase?
|
|
5.18.2
|
INF
|
What degree
of purity of additives is used for the preparation of
the mobile phase (salts, acids, buffer)?
|
|
5.18.3
|
I
|
Is the water
used in the preparation of the mobile phase of type 1?
|
|
5.18.4
|
R
|
Is the mobile
phase prepared daily?
|
|
5.18.5
|
INF
|
Is the pH
of the mobile phase previously checked for the realization
of the analytical runs?
|
|
5.18.6
|
R
|
Is filtration
of the mobile phase done?
|
|
5.18.7
|
INF
|
What are
the methods used for filtration of the mobile phase?
|
|
5.18.8
|
R
|
Is degassing
of the mobile phase done?
|
|
5.18.9
|
INF
|
What is the
procedure for degassing of the mobile phase?
|
|
5.18.10
|
INF
|
What cleaning procedure is adopted for cleaning the filter of the reservoir
of the mobile phase?
|
|
5.19. REFERENCE CHEMICAL SUBSTANCES
|
|
5.19.1
|
INF
|
Are Pharmacopoeic Reference Chemical Substances used?
|
|
5.19.2
|
I
|
Do the Work Chemical Substances (secondary standards)
have an analysis report?
|
|
5.19.3
|
INF
|
Are the secondary standards provided by an institution independent from
the contracting company?
|
|
5.19.4
|
N
|
Are the reference standards stored in adequate place?
|
|
5.19.5
|
R
|
Is there stock control for reference substances?
|
|
5.19.6
|
N
|
Is there a procedure for discarding expired standards?
|
|
5.20.
SAMPLES
|
|
N°
|
Qual
|
Items
|
|
5.20.1
|
N
|
Is there
record for receiving of samples?
|
|
5.20.2
|
R
|
Does the
laboratory have a check list for receiving of samples
(temperature record, identification and data of samples,
packaging conditions, etc)?
|
|
5.20.3
|
INF
|
What is the
storage temperature of biological samples?
|
|
5.20.4
|
I
|
Are the biological
samples stored in an adequate manner in freezers? Is temperature
control carried out with thermometers certified by INMETRO
or accredited laboratory (RBC)?
|
|
5.20.5
|
I
|
Do the samples
have adequate labeling containing all data necessary for
their identification?
|
|
5.20.6
|
INF
|
Are the biological
samples aliquoted? What is the procedure adopted?
|
|
5.20.7
|
N
|
In case of
re-analysis of samples, is it properly justified and registered?
|
|
5.20.8
|
N
|
In case of
loss of samples, is it properly justified and registered?
|
|
5.21. EXTERNAL TRANSPORT OF SAMPLES
|
|
N°
|
Qual
|
Items
|
|
5.21.1
|
INF
|
Is there
external transport of biological samples?
|
|
5.21.2
|
INF
|
Are the biological
samples pre-processed in their place of origin?
|
|
5.21.3
|
N
|
Is there
prior knowledge of the hours and dates of road or air
dispatch?
|
|
5.21.4
|
N
|
Are thermal boxes with adequate refrigeration material for the duration
of transport of biological samples?
|
|
5.21.5
|
R
|
Do the biological samples come with a temperature recording device during
the course of travel?
|
|
5.21.6
|
INF
|
What is the
method used for external transport of samples?
|
|
5.21.7
|
INF
|
What is the
average duration of external transport of samples?
|
|
5.22. INTERNAL TRANSPORT OF SAMPLES
|
|
N°
|
Qual
|
Items
|
|
5.22.1
|
INF
|
How is internal
transport of samples carried out?
|
|
5.23. VALIDATION OF ANALYTICAL METHODS
NAME OF STUDY AUDITED:
|
|
N°
|
Qual
|
Items
|
|
5.23.1
|
I
|
Does the laboratory have complete records of validations?
|
|
5.23.2
|
I
|
Are accuracy and precision studies carried out within acceptable limits?
|
|
5.23.3
|
N
|
Are analyses
done for determination of the limit of quantification?
|
|
5.23.4
|
N
|
Is a level
of recovery of the method determined?
|
|
5.24. STABILITY
|
|
5.24.1
|
I
|
Are studies of stability of freezing and thawing cycles of samples carried
out?
|
|
5.24.2
|
I
|
Are short-term stability studies carried out?
|
|
5.24.3
|
I
|
Do the stability studies concern the period between collection and analysis
of the last study sample (long-term stability)?
|
|
5.24.4
|
I
|
Is a study of drug stability in stock solutions carried out?
|
|
5.2425
|
I
|
Is post-processing stability study carried out?
|
|
5.25. BIOSAFETY
Collective Protection
|
|
N°
|
Qual
|
Items
|
|
5.25.1
|
R
|
Is there
a Biosafety Commission?
|
|
5.25.2
|
R
|
Does the
technical body of the laboratory undergo health tests
periodically?
|
|
5.25.3
|
R
|
Is there
a Vaccination Program for employees?
|
|
5.25.4
|
N
|
Is there
a Waste Treatment Program?
|
|
5.25.5
|
N
|
Is decontamination of biological waste produced during laboratory activities
carried out?
|
|
5.25.6
|
N
|
Is care taken
for conditioning and final disposal of chemical waste?
|
|
5.25.7
|
R
|
Are adequate
containers used for discarding broken glass ware?
|
|
5.25.8
|
N
|
Is there
an emergency shower and eye-wash?
|
|
5.25.9
|
N
|
Are Fire
Extinguishers, sand buckets and granulated absorbents
available?
|
|
5.25.10
|
N
|
Is prevention
and notification of accidents done?
|
|
5.25.11
|
R
|
Are there
educative signs for preventing
risks?
|
|
5.25.12
|
N
|
Is there
information on how to act in case of emergency, such as:
hospital telephone, proto-help and fire brigade?
|
|
5.25.13
|
R
|
Are first-aid
boxes available in case of accidents?
|
|
5.26.
INDIVIDUAL PROTECTION
|
|
N°
|
Qual
|
Items
|
|
5.26.1
|
N
|
Does the laboratory train and guide the employees in the use the IPE
(Individual Protection Equipment)?
|
|
5.26.2
|
N
|
Do the employees
use long jackets with long sleeves?
|
|
5.26.3
|
N
|
Do the employees
use disposable gloves?
|
|
5.26.4
|
N
|
Do the employees
use protective goggles or facial protection?
|
|
5.26.5
|
R
|
Do the employees
use masks?
|
|
5.26.6
|
N
|
Do the employees
use closed shoes or protective shoes?
|
|
5.26.7
|
N
|
Do the employees
use clothes that protect the legs (long trousers)?
|
|
5.26.8
|
R
|
Is the laboratory
responsible for washing uniforms used by the employees
of the laboratory?
|
|
5.27.
DOCUMENTATION
|
|
N°
|
Qual
|
Items
|
|
5.27.1
|
INF
|
What are
the methods for filing the chromatograms of studies and
remaining documents?
|
|
5.27.2
|
R
|
Is access
of documentation of studies made easy?
|
|
5.27.3
|
I
|
Is the study documentation filed for at least 5 years?
|
6. STATISTICS
|
6.1 GENERAL INFORMATION
|
|
N°
|
Qual
|
Items
|
|
6.1.1
|
INF
|
Name of the
Coordinator of the Statistical Phase:
|
|
6.1.2
|
INF
|
Qualification
of the Coordinator:
|
|
6.1.3
|
N
|
Is the Coordinator
qualified in the area of Statistics?
|
|
6.1.4
|
INF
|
Does the
Center have advice from a statistician?
|
|
6.1.5
|
INF
|
Attributions of the Coordinator of the Phase:
|
|
6.1.6
|
INF
|
Place of execution of the statistical phase:
Street/Avenue:
ZIP:
District:
|
|
Municipality:
FU:
E-mail:
|
|
6.1.7
|
INF
|
Software used:
|
|
6.2. DESIGN OF THE STUDY
|
|
N°
|
Qual
|
Items
|
|
6.2.1
|
N
|
Does the
coordinator participate in planning of the study? (Decisions
on the design of the experiment, size of the sample, etc)
|
|
6.2.2
|
N
|
Are there
criteria for the definition of the design of the experiment?
Which ones?
|
|
6.2.3
|
I
|
Is the method
of allocation of subjects for the sequence of intake of
medicines randomized? What is the procedure adopted?
|
|
6.3
DATA MANAGEMENT
|
|
N°
|
Qual
|
Items
|
|
6.3.1
|
N
|
Is there
SOP related to execution of the Statistical Phase and/or
obtaining of pharmacokinetic parameters?
|
|
6.3.2
|
N
|
Is there
a procedure for the review of data obtained on collection
times?
|
|
6.3.3
|
INF
|
How is transcription
of data of chromatograms to work spreadsheets done?
|
|
6.3.4
|
INF
|
What is the
procedure adopted in case of missing samples and/or problems
in chromatograms?
|
|
6.3.5
|
N
|
Are incidents
from the previous phases documented?
|
|
6.3.6
|
N
|
Does the
coordinator receive information with respect to incidents
from previous phases?
|
|
6.3.7
|
INF
|
How are pharmacokinetic
parameters obtained?
|
|
6.3.8
|
INF
|
How many
transcriptions of data are done as from the end of the
analytical run of subjects?
|
|
6.3.9
|
N
|
Is there
a record dated and signed for checking transcribed data?
|
|
6.3.10
|
INF
|
Is data transcription
done manually or by a digital interface?
|
|
6.3.11
|
INF
|
What are
the methods of filing information generated in the process?
|
|
6.4. STATISTICAL ANALYSIS
|
|
N°
|
Qual
|
Items
|
|
6.4.1
|
R
|
Is preliminary
(exploratory) analysis of data done before proceeding
to statistical representation?
|
|
6.4.2
|
INF
|
What are
the points addressed in preliminary analysis? Is there
graphical representation?
|
|
6.4.3
|
N
|
What criteria
are adopted for detection of atypical or conflicting values?
|
|
6.4.4
|
INF
|
What measures
are adopted for detecting atypical observations?
|
|
6.4.5
|
N
|
Is data transformed
for representation (ANOVA)?
|
|
6.4.6
|
I
|
In Variance
Analysis, are the effects of sequence (group), of subjects
within the sequence, of the period and treatment considered?
|
|
6.4.7
|
I
|
Is the ANOVA
based on the experimental design adopted in the assessed
study?
|
|
6.4.8
|
INF
|
Is analysis
of residues after representation done?
|
|
6.4.9
|
R
|
Is some method
used for establishing the presence of the effect of interaction
between period and treatment (residual effect)?
|
|
6.4.10
|
INF
|
What are
the methods used for determination of the reliability
Interval?
|
|
6.4.11
|
N
|
Is the software
used in the statistical analysis appropriate?
|
