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STANDAR PROSEDUR TEKNIK
ASEPTIK DANSAFE HANDLING CYTOTOXIC
WORKSHOP SAFE HANDLING OF CYTOTOXIC DRUGS
L. ENDANG BUDIARTI
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Injections
Aqueous bronchial inhalations
Baths and soaks for live organs andtissues
Irrigations for internal body cavities
(i.e., any space that does not freely
communicate with the environment
outside of the body)
Ophthalmics
Implants
CERTAIN PHARMACEUTICAL PRODUCTS MUST BESTERILE
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TWO CATEGORIES OF STERILE PRODUCTS
those that can be sterilized infinal container (terminally
sterilized)
those that cannot be terminallysterilized and must be
aseptically prepared
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Aseptic processing
Objective is to maintain the sterility of a
product, assembled from sterile components
Operating conditions so as to prevent microbial
contamination
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COMPOUNDED STERILE PREPARATIONS (CSPS)USP 797 (REVISED 2015 USP 39 PAGE 626
Scope : to all persons who prepare CSPs (e.g., pharmacists,pharmacy technicians, physicians, veterinarians, and nurses)
at all places where CSPs are prepared (e.g., hospitals and
other healthcare institutions, patient treatment sites, infusion
facilities, pharmacies, and physicians or veterinarians
practice sites).
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MAJOR EDITS TO THE CHAPTER INCLUDE
1. Collapsed compounded sterile preparations (CSP) microbial risk categories from
three to two and changed terminology. No sterile compounding is inherently low
risk .
- Category 1 CSPs have a shorter beyond use date (BUD) and may be prepared ina segregated compounding area;
- Category 2 CSPs have a longer BUD and must be prepared in a cleanroom
environment.
2. Removed specific information on handling of hazardous drugs and added
references to Hazardous DrugsHandling in Healthcare Settings 800.
3. Introduced terminology for in-use time : CSP must be used after it has beenopened or punctured.
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COMPOUNDED STERILE PREPARATIONS (CSPS)USP 797 (REVISED 2015)
1) microbial contamination (nonsterility),
2) excessive bacterial endotoxins,
3) variability from the intended strength of correct ingredients,
4) chemical and physical contaminants,
5) use of ingredients of inappropriate quality.
to prevent harm including death
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TYPES OF CONTAMINATION
ParticulateDust, skin, hair, make up
ChemicalOil, grease, metal ions, perfume
BiologicalBacteria, fungi, rodents???
Radiation
Ultraviolet light
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PARTICLE CHARACTERISTICS
50 micron particles are visible
Average human hair is about 100 microns
Time to fall 1 meter in still air 33 seconds for 10 micron particle
48 minutes for 1 micron particle
Humans generate >1x105 particles per minute when motionless (fullygowned)
Humans can generate >1x106
particles when walking in the cleanroom
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10
WHY ALL THE CONCERN ABOUT DUST?
Typical size relationship between
dust, bacteria and viruses
Virus
(0,006m to 0,03m)
Dust Particle
(0,5m to 500m)
Bacteria
(0,2m to 2m)
Dust Is a Bacteria Carrier
WHO
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Particle sizes
AIRBORNE CONTAMINANTS
WHO
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Contaminationrate
Filling chronology (time or units)
ContaminationContamination
Contamination rate increasing during filling
This could indicate a
contamination originated in the
liquid media path (i.e. wrong
aseptic connection to the mediatank, contamination in the
recirculation loop).
It is important to keep under
aseptic conditions the media
bulk tank at the end of filling,
while waiting the media fill
results, for verifying thishypothesis
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CONTAMINATION CONTROL
Personnel Control
Dress code
Personal Hygiene
Gowning
Environmental Control
Entrance and exit
Materials and supplies
Cleaning and maintenance
Atmospheric
People ~75%
Ventilation ~15%
Room Structure ~5%
Equipment ~5%
CONTAMINATION SOURCES
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SPECIFIC ISSUES RELATING TO THE MANUFACTURE OF
ASEPTICALLY PREPARED PRODUCTS:
Manufacturing environment
Clean areas
Personnel
Preparation and filtration of solutions Pre-filtration bioburden
Filter integrity/validation
Equipment/container preparation and sterilization
Filling Process
Validation of aseptic processes
Specific issues relating to Isolators, BFS and Bulk
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MANUFACTURING ENVIRONMENT
Classification of Clean Areas
Classified in terms of airborne particles (Table 2)
G r ad e A t r es t In o p er at i o n
m a x i m u m p e r m i t t e d n u m b e r o f p a r t i c l e s / m 3
0.5 - 5.0 m > 5 m 0.5 - 5.0 m > 5
A 3 500 0 3 500 0
B 3 500 0 350 000 2 000
C 350 000 2 000 3 500 000 20 000
D 3 500 000 20 000 not defined not defined
At rest - production equipment installed and operating
In operation - Installed equipment functioning in definedoperating mode and specified number of personnel present
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PREPARATION
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SYRINGE
NEVER TOUCH
Tip or Plunger
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CARA MEMINIMALKAN KONTAMINASI
Menghilangkan / membunuh micro organisme dari tangan hand washing
Menghilangkan / membunuh micro organisme dari objek swab objek, desinfeksi
Membuat steril alat yang akan digunakan
Mengurangi resiko terpapar micro organismeAlatPelindung Diri
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KEBERSIHAN TANGAN
Cuci tangan 6 langkah
Prosedur terpenting untuk mencegah transmisipenyebab infeksi (orang ke orang; objek ke orang)
Antiseptik, dan air mengalir
Bukti :cuci tangan menunjang penurunaninsiden MRSA di ICU
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RISK FACTOR
Batch size
Complexity of the compounding process
(e.g., number of manipulations involved; whether starting with nonsterileor sterile components)
Inherent nature of the drug being compounded
(e.g., whether the drug is susceptible to microbial growth; whether the
preparation will be preservative free)
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Complexity of the compounding operation
(e.g., multiple people in the cleanroom at the same time; multiple CSPs
being prepared at the same time; activity in the surrounding areas)
Length of time between the start of compounding
(including making a stock solution) and administration of the drug to the
patient
RISK FACTOR
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Pharmacy CompoundingUSP Risk Level Assessment
Risk Category Requirements, Guidance & Examples
Immediate-Use
For emergent use, or situations where low-risk
compounding would add risk due to delaysNo storage or batch compounding
Continuous compounding process lasting less than one hour
Aseptic technique utilized
Administer less than 1 hour after preparation begins, or
discard
Simple transfer of sterile nonhazardous drugs or diagnosticradiopharmaceuticals
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Low-Risk Level
Simple admixtures compounded using closed system
transfer methods
Prepared in ISO Class 5 LAFW
Located in ISO Class 7 buffer area with ISO Class 8ante area
Examples include reconstitution of single-dose vials of
antibiotics or other small-volume parenterals,
preparation of hydration solutions
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Low-Risk Level with
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Medium-Risk Level
Admixtures compounded using multiple additives
and/or small volumes
Batch preparations (e.g., syringes)
Complex manipulations (e.g., TPN)
Preparation for use over several days
Prepared in ISO Class 5Located in ISO Class 7 buffer area with ISO Class 8
ante area
Examples include pooled admixtures, parenteral
nutrition solutions using automated compounders,
batch-compounded preparations that do not contain
bacteriostatic components
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High-Risk Level
Non-sterile (bulk powders) ingredients
Open system transfers
Prepared in ISO Class 5Located in ISO Class 7 buffer area with separate ISO
Class 8 ante area
Examples include CSPs prepared from bulk, nonsterile
components or final containers that are nonsterile and
must be terminally sterilized
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Beyond Use Dates
Risk Category Room
TemperatureRefrigeration Frozen (10 C )
Immediate-Use 1 hour 1 hour N/A
Low-Risk 48 hours 14 days 45 days
Low-Risk with 12-
hour BUD 12 hours 12 hours N/A
Medium-Risk 30 hour 9 days 45 days
High-Risk 24 hours 3 days 45 days
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LABEL
Labels for single compounded preparations must, at a minimum, include the
following:
- Names ofactive ingredients,
-Amounts or concentrationsof active ingredients
- BUD and time,- Storage requirements, and
- Identification of responsible compounding personnel.
- Labels for batch-prepared
CSPs must also include:
- Control or lot number,- Appropriate auxiliary labeling (including precautions), and
- Device-specific instructions (when appropriate).
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THE JOINT COMMISSION VIEW IS THAT ALTHOUGH
SURVEYED IN THE PHARMACY, THESE NEW REQUIREMENTSWILL BE JUDGED IN THE FOLLOWING EC STANDARDS
Environment design of drug preparation rooms (EC.8.10)
Air quality testing and environmental monitoring of compounding
environment (EC.7.10 testing), (EC.9.10 monitoring)
Temperature testing of drug storage areas (EC.6.10)
Automated compounding deviceverification of accuracy, calibration
and maintenance (EC.6.10)
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IDENTIFIKASI, ASESMEN DAN PENGENDALIAN RISIKO
DALAM PROSES DISPENSING SITOSTATIKA
http://www.asia4safehandling.org/
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DANGER
Antineoplastic agents are typically used as cancer
chemotherapeutic agents.
Antineoplastic hazardous agents are genotoxic,
teratogenic, carcinogenic, or toxic to other target
organs even at very low concentrations
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7 GROUP OF ANTINEOPLASTIC
Alkylating agents:
Alkylating agents undergo alkylation by a nucleophilic substitution reaction with cellularconstituents, such as DNA base pairs, cell membranes, proteins, and proteins.
Antitumor antibiotics:
The antitumor antibiotics are synthesized from microorganisms. The antitumorantibiotics either break-up DNA strands, slow, or stop DNA synthesis.
Antimetabolites:
Antimetabolites are structurally similar to metabolites required for normal biochemicalreactions. Antimetabolites interfere with cellular processes such as cell division.
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7 GROUP OF ANTINEOPLASTIC
Nitrosoureas:
Nitrosoureas act similar to that of alkylating agents and slow down or stop enzymes that helprepair DNA.
Mitotic agents (plant alkaloids):
Plant alkaloids break DNA strands and prevent cell replication.
Hormonal agents:
Steroids lyse lymphoblasts and thus directly cause lymphoid malignancies.
Miscellaneous agents:Though mechanisms of miscellaneous agents are not well understood, these agents probablyinhibit DNA, RNA, and protein synthesis.
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PERSONAL PROTECTIVE EQUIPMENT PPE
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TABLE 1. EXAMPLES OF POTENTIAL ROUTES OF EXPOSURE BASED ON ACTIVITY
Activity Potential Route of ExposureDispensing Counting tablets and capsules from bulk containers
Compounding
Crushing tablets or opening capsules
Pouring oral or topical liquids from one container to another
Weighing or mixing components
Constituting or reconstituting powdered or lyophilized HDs
Withdrawing or diluting injectable HDs from parenteral containers
Expelling air or HDs from syringes
Contacting HD residue present on PPE or other garments
Deactivating, decontaminating, cleaning, and disinfecting areas contaminated with or suspected to be contaminatedwith HDs
Maintenance activities for potentially contaminated equipment and devices
Administration Generating aerosols during administration of HDs by various routes (e.g. injection, irrigation, oral, inhalation, or topical
application)
Performing certain specialized procedures (e.g., intraoperative intraperitoneal injection or bladder instillation)
Priming an IV administration set
Patient-care activities Handling body fluids (e.g., urine, feces, sweat, or vomit) or body-fluid-contaminated clothing, dressings, linens, and
other
Spills
Spill generation, management, and disposal
Receipt
Contacting with HD residues present on drug container, individual dosage units, outer containers, work surfaces, or
floors
Transport
Moving HDs within a healthcare setting
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SCOPE1. Responsibilities of Personnel
Handling Hazardous Drugs
2. Facilities
3. Environmental Quality and Control
4. Personal Protective Equipment
5. Hazard Communication Program
6. Personnel Training
7. Receiving
8. Labeling, Packaging, and Transport
9. Dispensing Final Dosage Forms
10.Compounding
11.Administering
12.Deactivation/Decontamination,
Cleaning, and Disinfection
13. Spill Control
14. Disposal
15. Documentation and Standard
Operating Procedures16. Medical Surveillance
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PERSONNEL
All personnel who handle HDs are responsible for :
understanding the fundamental practices and precautions
continually evaluating these procedures and the quality of final HDs toprevent harm to patients,
minimize exposure to personnel,
minimize contamination of the work and care environment.
TRAINING - UPDATED
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FACILITIES
CLEAN ROOM
CYTOTOXIC SAFETY CABINET
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LABEL TRANSPORTATION
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PERSONAL PROTECTIVE EQUIPMENT PPE
Double gloves
Nitril/latex
chemo
N95 : masker
Eye protection andface shield
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DECONTAMINATION
At a minimum, all contaminated (and potentially contaminated)work surfaces should be cleaned with detergent solution
followed by several rinses with clean water.
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SPILL MANAGEMENT ENVIRONMENT, CARE GIVER
PROTECTION
A N 9 5, R 95 , P9 5 d u s t m a s k , o r m o r e
p r o t e c t i v e h a l f /f u l l f a c e r e s p i r a t o r s
s h o u l d b e w o r n d u r i n g a n a n t i n eo p l a s t ic
d r u g s p i l l c l ea n u p .
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WASTE DISPOSAL
All materials contaminated with antineoplastic agents must be
disposed of as hazardous chemical waste.
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Antineoplastic drug waste solids and solutions : contained separately Outer gloves and sleeve covers : collected with antineoplastic drug
contaminated laboratory waste.
Containerize the waste : in a plastic bag, double bag; seal the bag and
place in a hard-sided sealable plastic container. Label and seal the box
for disposal.
Needles and syringes : in sharps container, also for disposal as
hazardous chemical waste.
The outside of antineoplastic agent waste containers must be cleaned
and free of contamination for disposal
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A written SOP for safe handling of antineoplastic agents should include:
laboratory staff training,
PPE, receiving and storage,
labeling,
preparation and manipulation of antineoplastic agents in physicochemical studies or
animals,
equipment used,
housekeeping practices,
glassware decontamination,
spill cleanup, and disposal of antineoplastic agents as hazardous waste.
SOPs for handling different forms of antineoplastic agents (i.e. tablet, injectable liquid,etc.) should also include anticipated
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GUIDELINES - ORAL CYTOTOXIC
i. safe prescribing of oral chemotherapy agents
ii. safe handling of chemotherapy agents
iii. safe administration of chemotherapy agents
iv. safe disposal of cytotoxic waste
Worksafe Victoria, Jan 2003, Handling cytotoxic Drugs in the Workplace
Prescribing, pharmacist and nurses who has the appropriate training and skills in
cancer chemotherapy
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R/ Dispensin
g
compounding administering monitoring Informasi
Edukasi
Dokter Keputusan terapi,
BSA/BB
Pembulatan
dosis, jml/cycle
Efek terapi, ESO
Semua profesi
sesuai SPO
Patologi, indikasi,
pengobatan
Apoteker Verifikasi
resep,
label
V
Perubahan
bentuk sediaan
Stop, missed dose ESO Pengobatan, efek yg
tdk diinginkan
Tertulis, verbal
Perawat v
Tdk menumbuk,
memotong
tablet
Hindari : kontak
kulit
lepasnya serbuk
di udara
kontaminsai dgn
obat lain
ESO suporting
Pasien x
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ORAL CYTOTOXIC
All layers : of the packaging must be clearly marked ascytotoxic including the outer bag that contains thesupply
The container should offer protection from the light
where required.- Where cytotoxic medication is supplied in glass
bottles then a pharmacist must confirm whetherother containers are suitable for dispensing orwhether it is essential that the glass bottle be used to
avoid any adverse affects on the drug
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6/1/2016
If a blister pack is used,- this must be filled by the pharmacist dispensing the
chemotherapy and- labeled with relevant instructions with a cytotoxic warning
label.- Other non cytotoxic medicationMUST NOT be placed into the
same pack
Oral chemotherapy agents should be stored:- as directed by the pharmacist,- in a secure manner,- out of the reach of children
Tablet containers should have child proof caps. Where this isnot the case, care should be taken to ensure that they arekept out of the reach of children
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LIMBAH
Semua sisa obat kembali ke farmasi pemusnahan (Any unused medication should be returned to thepharmacy for appropriate disposal)
Incenerator 1100C
Limbah kering:
Sarung tangan, plastik tempat obat, syringe, wadah obat (blister, botol, plastik)
Linen basah terkontaminasi:
Sprei, sarung bantal, baju, handuk
Urine, vomits, blood, sperm and other bodily fluids
7 hari sejak menggunakan kemoterapifull flush with the lid down
Permukaan terkontaminasi segera dibersihkan dengan air dan detergent
(Contaminated surfaces should be washed with copious amounts of water and with detergen) Transport limbah dari rumah ke rumah sakit : wadah tdk mudah pecah/robek dlm plastik ungu, terikat
kuat
Remember to thoroughly wash hands upon
commencement and completion of disposing of
drugs contaminated products and waste
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MARI DISKUSI