Bu Endang Standar Prosedur Teknik Aseptik Dan Safe Handling Cytotoxic New

7/25/2019 Bu Endang Standar Prosedur Teknik Aseptik Dan Safe Handling Cytotoxic New

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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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11

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

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Bu Endang Standar Prosedur Teknik Aseptik Dan Safe Handling Cytotoxic New