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CLEANING VALIDATION
The principles The principles The principles The principles and approaches to cleaning and approaches to cleaning and approaches to cleaning and approaches to cleaning validation : validation : validation : validation :
Protocol s and reports
Personnel and equi pment
Use of detergents
Mi crobi ol ogy
Sampl i ng
Anal yti cal methods and
Acceptabl e l i mi ts
CLEANING VALIDATION
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FDA 21 CFR 211. 67 (a)
Equipment and utensi ls shall be cleaned, mai ntained, and
sani tized at appropriate inter vals to prevent mal functions or
contami nati on that would alter the safety, identi ty, strength,
qual ity, or puri ty of the drug product beyond the offi cial or other
established requirements.
WHO, Annex 4, 4. 11
It is of critical impor tance that par ticular attenti on is paid to
the val idati on of analytical test methods, automated systems
and cleaning procedures.
CLEANING VALIDATION
GMP REQUIREMENTS
The obj ecti ves of GMP i ncl ude preventi on of possi ble
contami nati on and cross-contami nati on
Pharmaceuti cal products can be contami nated by a
vari ety of substances
contaminants (e.g. microbes, previous products (both API and
excipient residues), residues of cleaning agents, airborne
materials (e.g. dust and particulate matter), lubricants and
ancillary material, such as disinfectants
also contamination from decomposition residues from product
or detergents
INTRO INTRO INTRO INTRO
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Cl eani ng procedures must stri ctl y fol l ow careful l y
establ i shed and val i dated methods of executi on.
Thi s appl i es equal l y to the manufacture of
pharmaceuti cal products and acti ve pharmaceuti cal
i ngredi ents (APIs).
Val i dati on of cl eani ng methods provi des documented
evi dence that an approved cl eani ng procedure wi l l
provi de cl ean equi pment, sui tabl e for i ts i ntended use
INTRO
There shoul d be val i dated wri tten SOPs detai l i ng the
cl eani ng process for equi pment and apparatus.
Cl eani ng pol i cy and cl eani ng val i dati on procedure to
cover:
contact surfaces (products, drug products and API);
cleaning after product changeover;
between batches in campaigns (when the same formula is
being manufactured over a period of time and on different
days;
bracketing products for cleaning validation; and
periodic evaluation and revalidation of the number of batches
manufactured between cleaning validations.
INTRO
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Not necessarily for non- critical cleaning, e. g. between
batches of the same product (or different lots of the same
intermediate in a bulk process), or of floors, walls, the
outside of vessels, and following some intermediate steps.
However, cleaning inter vals and methods should be
determined.
At least three consecutive applications of the cleaning
procedure should be per formed and shown to be successful
to prove that the method is validated
INTRO
Approved by QC or QA and to cover, e.g.
disassembly of system;
pre-cleaning;
cleaning agent, concentration, solution volume, water quality;
time and temperature;
flow rate, pressure and rinsing;
complexity and design of the equipment;
training of operators; and
size of the system.
CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS
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The cl eani ng val i dati on protocol shoul d i ncl ude:
objectives, responsible people;
description of the equipment including the make, model, serial
number or other unique code;
time intervals; bioburden; cleaning procedures;
equipment used for routine monitoring (e.g. conductivity
meters, pH meters and total organic carbon analysers);
number of cleaning cycles; sampling procedures (e.g. direct
sampling, rinse sampling, in process monitoring and sampling
locations)
analytical methods;
acceptance criteria (with rationale for setting the specific
limits) including a margin for error and for sampling efficiency;
revalidation requirements.
CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS
Cleaning agent used, scientifically justified and based
on:
the solubility of the materials to be removed;
the design and construction of the equipment and surface
materials to be cleaned;
the safety of the cleaning agent;
the ease of removal and detection;
the product characteristics;
the minimum temperature and volume of cleaning agent and
rinse solution; and
the manufacturer's recommendations
CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS
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No need for i ndi vi dual val i dati on for very si mi l ar cl eaning
procedures for products and processes.
Worst case val i dati on study may be acceptabl e and
shoul d be j usti fi ed. Thi s study referred as bracketi ng as
i t addressi ng critical issues rel ati ng to the sel ected
product, equi pment or process such as:
smallest batch size, smallest number of maximum daily doses,
hardest to clean product
equipment that contribute most to cross contamination of the
next product
Al l owed onl y where products are si mi l ar i n nature or
property and processed on the same equi pment; and
i denti cal cl eani ng procedures used.
CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS CLEANING VALIDATION PROTOCOLS
Bracketing
Use of worst case (e. g. small est batch si ze, small est number
of maximum daily doses, hardest to cl ean) product as a marker
for easier other products
Grouping of products
For example grouping based on; those products capable of causing the
largest possible problems if contaminated, or if they contaminate other
products; drug solubility and; equipment.
Identification of items of equipment that contribute most to
cross contamination of the next product
Identification of worst case locations in equipment , i . e. the
design of the equipment should be carefully examined.
Cri tical areas (those hardest to clean) should be identifi ed,
particularly in large systems that employ semi- automatic or fully
automatic clean- in- place (CIP) systems.
CLEANING VALIDATION CLEANING VALIDATION CLEANING VALIDATION CLEANING VALIDATION
PROTOCOLS PROTOCOLS PROTOCOLS PROTOCOLS
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The rel evant cl eani ng records ( si gned si gned si gned si gned by the operator, by the operator, by the operator, by the operator,
checked checked checked checked by producti on and by producti on and by producti on and by producti on and reviewed reviewed reviewed reviewed by qual ity by qual ity by qual ity by qual ity
assurance) assurance) assurance) assurance) and source data (original results) and source data (original results) and source data (original results) and source data (original results) shoul d be
kept.
The resul ts of the cl eani ng val i dati on shoul d be
presented i n cl eani ng val i dati on reports stati ng the
outcome and conclusion. outcome and conclusion. outcome and conclusion. outcome and conclusion.
CLEANING VALIDATION REPORTS CLEANING VALIDATION REPORTS CLEANING VALIDATION REPORTS CLEANING VALIDATION REPORTS
Personnel or operators who per form cleaning routinely should
be trained and should be effectively super vised.
CLEANING CLEANING CLEANING CLEANING VALIDATION VALIDATION VALIDATION VALIDATION - -- - PERSONNEL PERSONNEL PERSONNEL PERSONNEL
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Only procedures for the cleaning of surfaces of the equipment
that come into contact with product need validation.
non- contact parts of the equipment which product or any
process material may migrate also need to consider
Critical areas should be identified such as large systems
employing semi- automatic or fully automatic clean- in- place
systems
Dedicated equipment for:
products which are difficult to clean,
equipment which is difficult to clean,
products with a high safety risk where it is not possible to achieve
the required cleaning acceptance limits using a validated cleaning
procedure.
CLEANING CLEANING CLEANING CLEANING VALIDATION VALIDATION VALIDATION VALIDATION- -- - EQUIPMENT EQUIPMENT EQUIPMENT EQUIPMENT
There shoul d be one process for cl eani ng a pi ece of
equi pment or system as i t depends on the products
bei ng produced, whether
cleaning occurs between batches of the same product, or
cleaning between batches of different products.
The desi gn of equi pment may i nfl uence the effecti veness
of the cl eani ng process.
Consi der desi gn when prepari ng the cl eani ng val i dati on
protocol
CLEANING VALIDATION CLEANING VALIDATION CLEANING VALIDATION CLEANING VALIDATION- -- - EQUIPMENT EQUIPMENT EQUIPMENT EQUIPMENT
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Rel eased by qual i ty control and meet food standards or
regul ati ons
Composi ti on known
Easi l y removed wi th ri nsi ng - demonstrated - wi th
acceptabl e l i mi ts defi ned
If persi stent resi dues (e.g. cati oni c detergents) - avoi ded
Acceptabl e l i mi ts for detergent resi dues after cl eani ng
shoul d be dened
Consi der al so detergent breakdown
CLEANING CLEANING CLEANING CLEANING VALIDATION VALIDATION VALIDATION VALIDATION- -- - DETERGENTS DETERGENTS DETERGENTS DETERGENTS
Need to i ncl ude measures to prevent mi crobi al growth
and remove contami nati on
Documented evi dence of mi crobi al prol i ferati on
preventi on of
routine cleaning
storage of equipment
Equi pment stored i n a dry condi ti on after cl eani ng (no
stagnant water)
Control of bi oburden through adequate cl eani ng and
appropri ate storage of equi pment
The val i dati on procedures al so must i ncl ude the peri od
and condi ti ons
storage of unclean equipment before cleaning
between cleaning and equipment reuse
CLEANING CLEANING CLEANING CLEANING VALIDATION VALIDATION VALIDATION VALIDATION- -- - MICROBIOLOGY MICROBIOLOGY MICROBIOLOGY MICROBIOLOGY
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Cl ean as soon as possi bl e after use
especially topical products, suspensions and bulk drug or
where the drying of residues will directly affect the efficiency
of a cleaning procedure
Two methods of sampl i ng:
direct surface sampling and
rinse samples
Combi nati on of the two - most desi rabl e
CLEANING VALIDATION-SAMPLING
Di rect sur face sampl i ng (di rect method) Di rect sur face sampl i ng (di rect method) Di rect sur face sampl i ng (di rect method) Di rect sur face sampl i ng (di rect method)
Most commonly used method
Use swabs (i nert materi al ) - type of sampl i ng materi al
shoul d not i nterfere wi th the test
Factors to be consi dered i ncl ude:
supplier of the swab,
area swabbed, number of swabs used, whether they are wet or
dry swabs,
swab handling and swabbing technique
location from which the sample is taken (including worst case
locations, identified in the protocol)
composition of the equipment (e.g. glass or steel)
Cri ti cal areas (hardest to cl ean) shoul d be i denti fi ed
e.g. in semi-automatic/fully automatic clean-in-place systems
Use appropri ate sampl i ng medi um and sol vent
CLEANING VALIDATION-SAMPLING
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Ri nse sampl es (i ndi rect method) Ri nse sampl es (i ndi rect method) Ri nse sampl es (i ndi rect method) Ri nse sampl es (i ndi rect method)
Al l ows sampl i ng of:
a large surface
areas that are inaccessible or that cannot be routinely
disassembled
Provi des an "overal l pi cture"
Useful for checki ng for resi dues of cl eani ng agents
Shoul d be used i n combi nati on wi th other sampl i ng
methods such as surface sampl i ng
It i s i mportant to ensure chosen sol vent has appropri ate
recovery for resi dues bei ng quanti fi ed
CLEANING VALIDATION-SAMPLING
Anal yti cal method must be val i dated before the cl eani ng
val i dati on i s performed
Val i dated anal yti cal methods abl e to detect resi dual s
or contami nants:
specific for the substance(s) being assayed
at an appropriate level of cleanliness (sensitivity)
Sui tabl e methods that are sensi ti ve and speci fi c shoul d
be used for:
chromatographic methods (e.g. high pressure liquid
chromotography (HPLC), gas chromotography (GC), and high
pressure thin-layer chromatography (HPTLC)). Others include
(alone or in combination), e.g. total organic carbon (TOC), pH,
conductivity, ultraviolet (UV) spectroscopy, and ELISA
CLEANING VALIDATION
ANALYTICAL ANALYTICAL ANALYTICAL ANALYTICAL METHODS METHODS METHODS METHODS
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Acceptance criteria established for contaminant levels in
the sample should be:
Practical, achievable and verifiable
The rationale for the residue limits established should be
Logical, based on knowledge of materials
Each situation assessed individually
There should be no residue from:
Previous product
Reaction by-products and degradants
Cleaning process itself (e.g. detergents or solvents)
CLEANING VALIDATION
ACCEPTABLE LIMITS CCEPTABLE LIMITS CCEPTABLE LIMITS CCEPTABLE LIMITS
Li mi ts may be expressed as:
a concentration in a subsequent product (ppm),
limit per surface area (mcg/cm
2 22 2
), or
in rinse water as ppm.
Li mi ts for carry-over of product resi dues shoul d meet
defi ned cri teri a:
Visually clean Visually clean Visually clean Visually clean No residue visible on equipment after cleaning.
Spiking studies to determine the concentration at which most
active ingredients are visible. (May not be suitable for high
potency, low-dosage drugs.)
No more than No more than No more than No more than 10 10 10 10 ppm ppm ppm ppm of one product will appear in another
product (basis for heavy metals in starting materials).
No more than No more than No more than No more than 0.1 0.1 0.1 0.1% %% % of the normal therapeutic dose of one
product will appear in the maximum daily dose of a subsequent
product.
CLEANING VALIDATION
ACCEPTABLE LIMITS CCEPTABLE LIMITS CCEPTABLE LIMITS CCEPTABLE LIMITS
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Certai n allergenic ingredients and highly potent material
shoul d be undetectable by the best available analytical
methods
e.g. penicillins and cephalosporins
e.g. anovulent steroids, potent steroids and cytotoxics
Dedi cated manufacturi ng faci l i ti es needed
CLEANING VALIDATION
ACCEPTABLE LIMITS CCEPTABLE LIMITS CCEPTABLE LIMITS CCEPTABLE LIMITS
Verifying that manufacturing equipment and product formulation are
finalized
Installation qualification, operational qualification, and preventive
maintenance of instruments
Validation of analytical methods
Evaluation of cleaning procedures themselves
PRIOR PREPARATION FOR PRIOR PREPARATION FOR PRIOR PREPARATION FOR PRIOR PREPARATION FOR OF OF OF OF CLEANING CLEANING CLEANING CLEANING
VALIDATION VALIDATION VALIDATION VALIDATION
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COMPUTERIZED SYSTEM
VALIDATION
The validation The validation The validation The validation of computerized systems of computerized systems of computerized systems of computerized systems i nclude: i nclude: i nclude: i nclude:
System speci fi cati ons
Functi onal speci fi cati ons
Securi ty
Back-ups
Val i dati on:
Hardware
Software
INTRO
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Computer systems shoul d be val i dated at the l evel
appropri ate for thei r use and appl i cati on.
Computer systems used i n pl anni ng, speci fi cati on,
programmi ng, testi ng, commi ssi oning, document
operati on, moni tori ng and modi fyi ng.
The purpose: i s to ensure an acceptabl e degree of
evi dence (documented, raw data), confi dence
(dependabi l i ty and thorough, ri gorous achi evement of
predetermi ned specs), i ntended used, accuracy,
consi stency and rel i abi l i ty
Both the system specifications and functional
specifications should be validated.
Periodic (or continuous) evaluation should be per formed
after the initial validation.
INTRO
INTRO
Shoul d be wri tten procedures for:
performance monitoring, change control, programme and
data security, calibration and maintenance, personnel
training, emergency recovery and periodic re-evaluation
Duri ng val i dati on, consi der:
networks
manual back-ups
input/output checks
process documentation, monitoring
alarms, and
shutdown recovery
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Also known as Control document
Control document should state
objectives of a proposed computer system
the data to be entered and stored
the flow of data
how it interacts with other systems and procedures
the information to be produced
the limits of any variable
the operating programme and test programme
System elements that need to be considered in computer
validation include:
hardware (equipment)
software (procedures)
people (users)
COMPUTERIZED SYSTEM VALIDATION
SYSTEM SYSTEM SYSTEM SYSTEM SPECIFICATION SPECIFICATION SPECIFICATION SPECIFICATION
COMPUTERI ZED SYSTEM COMPUTERI ZED SYSTEM COMPUTERI ZED SYSTEM COMPUTERI ZED SYSTEM VALI DATI ON VALI DATI ON VALI DATI ON VALI DATI ON
FUNCTI ONAL FUNCTI ONAL FUNCTI ONAL FUNCTI ONAL SPECI FI CATI ON (PERFORMANCE SPECI FI CATI ON (PERFORMANCE SPECI FI CATI ON (PERFORMANCE SPECI FI CATI ON (PERFORMANCE
SPECI FI CATI ON SPECI FI CATI ON SPECI FI CATI ON SPECI FI CATI ON) )) )
Provi de i nstructi ons for:
testing, operating, and maintaining the system
names of the person(s) (development and operation)
When usi ng computer systems, consi derati on:
location
power supply (Fluctuations in the electrical supply can
influence computer systems and power supply failure can
result in loss of memory).
temperature
magnetic disturbances
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GMP requi rements for computer systems:
Veri fication and reval idati on Veri fication and reval idati on Veri fication and reval idati on Veri fication and reval idati on
After a suitable period of running a new system
Independently reviewed and compared with the system
specification and functional specification
Change control Change control Change control Change control
Alterations made in accordance with a defined procedure
Provision for checking, approving and implementing the
change
Checks Checks Checks Checks
Data checked periodically
Confirm accurate and reliable transfer
COMPUTERI ZED SYSTEM VALI DATI ON COMPUTERI ZED SYSTEM VALI DATI ON COMPUTERI ZED SYSTEM VALI DATI ON COMPUTERI ZED SYSTEM VALI DATI ON
FUNCTI ONAL SPECI FI CATI ON (PERFORMANCE FUNCTI ONAL SPECI FI CATI ON (PERFORMANCE FUNCTI ONAL SPECI FI CATI ON (PERFORMANCE FUNCTI ONAL SPECI FI CATI ON (PERFORMANCE
SPECI FI CATI ON) SPECI FI CATI ON) SPECI FI CATI ON) SPECI FI CATI ON)
Security is impor tant in production as well as in quality
control
Data entered or amended - only by authorized persons
Security systems to prevent unauthorized entr y or
manipulation of data
SOPs for entering data, changing or amending incorrect
entries and creating back- ups
Security procedures should be in writing
Security should also the control access of devices used to
store programmes, such as tapes, disks and magnetic strip
cards.
COMPUTERIZED SYSTEM COMPUTERIZED SYSTEM COMPUTERIZED SYSTEM COMPUTERIZED SYSTEM VALIDATION VALIDATION VALIDATION VALIDATION
SECURITY SECURITY SECURITY SECURITY
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Traceabi l i ty i s of parti cul ar i mportance and shoul d be
abl e to:
identify the persons who made entries
identify the persons who made changes
identify the persons who released material
identify the persons who performed other critical steps in
production or control
Independent veri fi cati on and rel ease for use by a second
authori zed person
e.g. for entry of a master processing formula.
SOPs for certai n systems or processes val i dated
e.g. action in case of system failure or breakdown including
disaster recovery procedure in the event of a breakdown
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
SECURITY SECURITY SECURITY SECURITY
Regul ar back-ups of al l fi l es and data
Secure storage (prevent intentional or accidental damage)
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
BACK UPS
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Val i dati on process shoul d i ncl ude:
Planning
Validation policy
Project plan and SOPs
Defi ne computer-rel ated systems and vendors
Vendor and product eval uated
System desi gned and constructed
Consider types, testing and quality assurance of the software
After i nstal l ati on of the system i t shoul d be qual ifi ed.
Extent of qual i fi cati on depends on compl exi ty of the
system
COMPUTERIZED SYSTEM COMPUTERIZED SYSTEM COMPUTERIZED SYSTEM COMPUTERIZED SYSTEM VALIDATION VALIDATION VALIDATION VALIDATION
PROCESS PROCESS PROCESS PROCESS
Qual i fi cati on i ncl udes:
Instal l ati on
Eval uati on of the system
Performance
Change control , mai ntenance and cal i brati on, security,
conti ngency pl anni ng, SOPs, trai ni ng, performance
moni tori ng and peri odi c re-eval uati on
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
PROCESS PROCESS PROCESS PROCESS
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Validation of hardware Validation of hardware Validation of hardware Validation of hardware
Appropri ate tests and chal l enges to the hardware
No i nfl uence of stati c, dust, power-feed vol tage
fl uctuati ons and el ectromagneti c i nterference
Hardware i s consi dered to be equi pment
focus on location, maintenance and calibration as part of the
qualification
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
PROCESS PROCESS PROCESS PROCESS
Validation of Validation of Validation of Validation of hardware hardware hardware hardware
It shoul d prove:
Appropri ate capaci ty
Operati onal l i mi ts
e.g. memory, connector ports, input ports
Performance under worst-case condi ti ons
e.g. long hours, temperature extremes
Reproduci bi l i ty/consi stency
e.g. by performing at least three runs under different
conditions
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
PROCESS PROCESS PROCESS PROCESS
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Validation of Validation of Validation of Validation of hardware hardware hardware hardware
Wri tten qual i fi cati on protocol s; resul ts i n qual i ficati on
reports kept
Reval i dati on i n case of si gni fi cant changes
Val i dati on may be performed by the vendor but
ul ti mate responsi bi l i ty remai ns wi th the company
If records kept by suppl i er, manufacturer sti l l has to
have suffi ci ent records to al l ow assessment of the
adequacy of the val i dati on
A mere certi fi cati on of sui tabi l i ty from the vendor, for
exampl e, wi l l be i nadequate
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
PROCESS PROCESS PROCESS PROCESS
Validation of Software Validation of Software Validation of Software Validation of Software
Software:
i s the term used to descri be the compl ete set of
programmes used by a computer, and whi ch shoul d be
l i sted i n a menu
Records are consi dered as software
Focus shoul d be pl aced on:
accuracy, security, access, retention of records, review, double
checks, documentation and accuracy of reproduction
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
PROCESS PROCESS PROCESS PROCESS
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Validation of Software Validation of Software Validation of Software Validation of Software
Key computer programmes to be i denti fi ed:
language, name, function (purpose of the programme)
input (determine inputs), output (determine outputs)
fixed set point (process variable that cannot be changed by the
operator), variable set point (entered by the operator)
edits (reject input/output that does not conform to limits and
minimize errors, e.g. four- or five-character number entry),
input manipulation (and equations) and programme overrides
(e.g. to stop a mixer before time)
Identi fi cati on of authori zed personnel
to write, alter or have access to programmes
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
PROCESS PROCESS PROCESS PROCESS
Validation of Validation of Validation of Validation of Software Software Software Software
Points to be consi dered may i ncl ude: Points to be consi dered may i ncl ude: Points to be consi dered may i ncl ude: Points to be consi dered may i ncl ude:
Consistency in performance: Within pre-established limits)
Function: Matching the assigned operational function (e.g.
generate batch documentation, different batches of material
used in a batch listed)
Worst case: Validation under different conditions (e.g. speed,
data volume, frequency)
Repeats: Sufficient number of times (e.g. replicate data
entries)
Documentation: Protocols and reports
Revalidation: In case of significant changes made
COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION COMPUTERIZED SYSTEM VALIDATION
PROCESS PROCESS PROCESS PROCESS
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WHO Technical Repor t Series, No. 937, 2006. Annex 4
http: //www. fda. gov/Drugs/Gui danceCompl i anceRegul ator yInfo
rmati on/Gui dances/defaul t. htm
REFERENCES