MOHD NASRUL MOHAMAD NOOR

Transcription

1 QUALITY ASSURANCE IN ASEPTIC WHO Collaborating Centre For Regulatory Control of Pharmaceuticals DISPENSING : MAINTENANCE OF CLEAN ROOM & EQUIPMENT Member of Pharmaceutical Inspection Cooperation Scheme MOHD NASRUL MOHAMAD NOOR ASEPTIC DISPENSING COURSE MS ISO 9001:2008 Certified 26 th APRIL

2 MAINTENANCE of CLEAN ROOM & EQUIPMENT Cleaning & Sanitization Monitoring activity Maintenance Maintenance of HVAC System Performance testing Others Maintenance: Monitoring devices etc

3 CLEANING AND SANITATION

4 OVERVIEW OF PIC/S GPP GUIDELINE REGARDING CLEANING Washing and cleaning activities should not themselves be a source of contamination. PIC/S GPP Chapter 3 Written procedures should be available in particular for cleaning, disinfecting and maintenance of equipment (e.g. water demineralisation equipment, distillation equipment, refrigerator) and facilities PIC/S GPP Chapter 4

5 OVERVIEW OF PIC/S GPP GUIDELINE REGARDING CLEANING...cont. Before any processing operation is started, it is important to ensure (and document) that the work area and the equipment are clean and free from any starting materials and products not required for the current operation and that all equipment is functioning satisfactorily. Potential problems should be reported to key personnel. PIC/S GPP Chapter 5 Clean areas should be regularly cleaned according to a documented and approved procedure. Any staff performing cleaning duties should have received documented training including the relevant elements of GMP and should have been assessed as competent before being allowed to work alone. PIC/S GPP Annex 1, Section 2

6 CLEANING PROGRAMME In summary, a cleaning programme shall have: Clear Written Documentation Cleaning and Sanitation SOPs Cleaning and Sanitation Schedules Cleaning and Sanitation Logs / Records Training of Cleaning Personnel Record Status labelling if necessary (in the form of tags, or labels)

7 CLEANING PROGRAMME : Frequency After production or daily Weekly Monthly CLEAN ROOM Area Floors Windows Door knobs Floors Windows Door knobs Walls Floors Windows Door knobs Walls Ceiling

8 CLEANING PROGRAMME : EQUIPMENT Frequency Before and after production After production or daily Weekly Equipment/ Area Laminar Air Flow Cabinets / Biohazard Safety Cabinets / CDR Safety Cabinets / Isolators Stainless steel stools/chairs in preparation room Trolleys in preparation room Pass box Clinical waste bins Laminar Air Flow Cabinets / Biohazard Safety Cabinets / CDR Safety Cabinets / Isolators Stainless steel stools / chairs Trolley Pass box Clinical waste bins Sinks Gowning cabinet Changing room cabinet

9 EXAMPLE OF CLEANING RECORD

10 CLEANING EQUIPMENT Dedicated equipment should be used and stored to minimise microbiological contamination. Mop heads should be disposed of or re-sterilised after each cleaning session. PIC/S GPP Annex 1, Section 2 Washing and cleaning equipment should be chosen and used in order not to be a source of contamination Vacuum or wet cleaning methods are preferred Vacuum cleaners or polishers should be fitted with dust/hepa filters

11 CHOOSING THE RIGHT TOOLS -WIPERS WIPERS- Lint-free Preferably sterile

12 CHOOSING THE RIGHT TOOLS -MOPPING SYSTEM- Usually used for floors and walls, lint-free Hardware may consist of stainless steel, anodized aluminium, plastic or fiberglass Large, small and double bucket system available For wall mops: Sponge type mops with /without fabric cover Pad or covered bar mops PVA foam mops For floor mops: Tubes or knitted polyester as string mop PVA foam mops Pad or covered bar mops Polyester strip mops

13 EXAMPLE OF CLEANING MATERIAL Lint free cleaning wipes for wiping surfaces Floor Particle Rollers Bench Particle Rollers Removable cover for VertiKlean Mop Sterile (MVK-QT-SOX) Handle Aluminum & 12 inch VertiKlean Mop (MVK-MOPIR) Head for walls, and ceilings

14 DISINFECTANT Cleaning and disinfecting agents should be free from viable micro organisms and those used in Grade A and B areas should be sterile and spore free. Periodic use of sporicidal cleaning agents should be considered to reduce contamination from spore forming microorganisms. For sterile alcohol sprays and other materials brought into clean areas an in-use expiry date should be defined. PIC/S GPP Annex 1, Section 2

15 DISINFECTANT SELECTION CRITERIA Should be qualified and approved by QC Controlled with expiry dates Rotation of disinfectant shall be considered-to avoid microbial resistant SOPs for use shall follow manufacturer instruction Storage as per manufacturer instruction Shall be color-coded for easy identification by cleaners Preparation and dilution shall be performed by cleaners and must be supervised by the immediate superior or appointed personnel

16 Disinfectant A DISINFECTANT PROPERTIES Activity Bactericidal Fungicidal Virucidal Sporicidal Alcohol Good Good Good None Aldehydes Good Good Good Good Amphoretic surfactants Good Fair Fair None Biguanides Good Fair Good None Chlorine dioxide / quatblend Good Good Good Good Hypochlorites Good Good Good Fair Hydrogen peroxide / peracitic blend Phenolic compound Quartenary Ammonium Cpd Good Good Good Good Good Good Fair None Good Good Good None

17 EXAMPLE OF DISINFECTANTS Sterile Isopropyl Alcohol 70% (Klercide 70/30) for equipments, work bench and surface Sterile Biocide A - broad spectrum, mixture of a quaternary ammonium compound and a biguanide (bactericidal and fungicidal activity) Sterile Biocide B- broad spectrum, mixture of stabilised chlorine dioxide and a quaternary ammonium compound (sporicidal, bactericidal, virucidal and fungicidal)

18 EFFECTIVE CLEANING METHOD One general rule shall be followed for wiping and mopping path Cleanest / Driest Dirtiest / Wettest

19 CLEANING METHOD : CLEAN ROOM Wiping Ceilings Use unidirectional strokes Wring mop after each pass Mopping walls & windows Wipe from top to bottom (cleanest to dirtiest) Wring after each pass to prevent redisposition of particles Use of overlapping strokes Mopping Floors From inside to outside (cleanest to dirtiest) Unidirectional and use of over lapping strokes

20 CLEANING METHOD : PASS-BOX The pass-box should be disinfected before production in the morning.

21 HOW TO SWAB HORIZONTAL LAMINAR AIRFLOW CABINET?

22 HORIZONTAL LAFC Cleanest Dirtiest

23 SWABBING HORIZONTAL LAFC

24 SWABBING HORIZONTAL LAFC 2 1 3

25 SWABBING HORIZONTAL LAFC

26 PROPER SWABBING OF HORIZONTAL LAFC Use only lint-free wipes spray with disinfectant. Single surface swabbing only. Do not overwet the wipes. Do not spray into the cabinet (will clog the HEPA filter).

27 VERTICAL LAFC Cleanest Dirtiest

28 SWABBING VERTICAL LAFC 1 2 3

29 PROPER CLEANING OF CYTOTOXIC DRUG SAFETY CABINET Consider to wipe beneath the front and rear grilles regularly. Ensure adequate protection Ensure adequate protection by donning proper PPE

30 PROPER CLEANING OF ISOLATOR Transfer Chamber Gloves Front visor

31 PROPER CLEANING OF ISOLATOR 1. Inner surfaces of both transfer chambers 2. Inner surface of isolator i. Back ii. iii. iv. Left and right side Front visor Glove sleeves v. Working bench 3. External surfaces of the transfer chambers and front visor

32 CLEANING VERIFICATION The effectiveness of cleaning should be routinely demonstrated, by microbiological surface sampling e.g. contact plates or swabs. PIC/S GPP Annex 1, Chapter 2 Cleaning verification is required in order to monitor the effectiveness of cleaning. Can be accomplished by: a) Visual inspection b) Non Viable Particle Monitoring (Particle Count) c) Microbial Monitoring Air, Surface

33 CLEANING VERIFICATION Visual Inspection Visual inspection of cleaning effectiveness may be adequate for many clean areas or uncontrolled areas Visual inspection can be used to determine if gross Visual inspection can be used to determine if gross cleaning was completed

34 CLEANING VERIFICATION Non-Viable Particle Monitoring Particle counting is a reliable method of checking for microscopic particles In house staff should conduct periodic checks to catch unknown contamination Microbial Monitoring Airborne viable microorganism can be monitored by using two different techniques; active air sampling or passive air sampling Surface sampling can be done by swabing or contact plate depending on the surface Personnel contamination can also be monitored by using contact plate

35 MAINTENANCE of HVAC, MONITORING DEVICES etc.

36 HVAC SYSTEM Should be regularly maintained (PPM) Must obtain PPM schedule from contractor or HSS Include: Visual inspection of primary filters and wash if necessary Periodic changing of secondary filters if necessary Annual check for Air Handling Unit (AHU) Motor, fan belt, etc Annual HEPA filter leak test and change if necessary All maintenance done must be recorded and retained

37 MONITORING DEVICES Should be regularly calibrated (PPM) Must obtain PPM schedule from contractor or HSS Include: Pressure gauges Thermometer Hygrometer Particle counter Air sampler Calibration procedure and certificate must be recorded and retained

38 OTHER ACCESSORIES Should be regularly maintained (PPM) Must obtain PPM schedule from contractor or HSS Include: Fire safety system Emergency alarm system Interlocking door system All maintenance done must be recorded and retained

39 CLEAN ROOM & EQUIPMENT PERFORMANCE TESTING

40 CLEAN ROOM / EQUIPMENT PERFORMANCE TESTING Recertification of Clean Room / Cabinet / Isolator Should be performed: After finished installation, before using the facility Annually as routine procedure After major renovation to clean room After major overhaul of HVAC system After room has been inoperative for extended time Done by a third party tester with NEBB or NATA accreditation Reports must be complete with: Tests layout and procedures Raw data Calibration certificates of equipments used

41 CLEAN ROOM TEST CONDITION As Built At Rest In Operation AS BUILT AT REST IN OPERATION

42 TESTS PERFORMED CLEAN ROOM EQUIPMENT Airborne Particle Count HEPA Filter Leak Test (PAO Challenge) Air Change Rate Airflow velocity Room Pressurization Test Airflow pattern (additional for negative pressure cabinet) Temperature Isolator leak test Humidity Glove integrity (Isolator) Light Intensity Test

43 AIRBORNE PARTICLE COUNT To measure the airborne particulate level in the clean room and to determine the room cleanliness classification Equipment Used: Discrete Particle Counter Minimum of 3 samples shall be taken

44 AIRBORNE PARTICLE COUNT...cont. Acceptance Criteria: At Rest In Operation Grade Max Permitted no. of particles per m 3 (per ft 3 ) 0.5 um 5um 0.5um 5um A B C D Not Defined Not Defined PIC/S GUIDE TO GOOD PRACTICES FOR THE PREPARATION OF MEDICINAL PRODUCTS IN HEALTHCARE ESTABLISHMENTS; PE 010-3;1 ST October 2008)

45 AIR CHANGE RATE Amount of air cycled in room per hours For flushing of particulate matters from air Performance depend on design of AHU system To attain good air flow pattern and pressure differentials The limits of the ACR taken from Australian Standard AS are as follows: Grade A : > 120 / hour Grade B : > 40 / hour Grade C : > 20 / hour Grade D : > 20 / hour

46 HEPA FILTER LEAK TEST To verify the absence of bypass leakage (between filter frame and ceiling grid system) in the installation of the filters and confirm that the filters are free of defects and small leaks Challenge Aerosol: PAO Instrument use: Photometer, Aerosol Generator, Aerosol Challenge Agent (Emery 3004) Acceptance criteria to be: The downstream penetration must not exceed 0.01% of total upstream concentration

47 ROOM PRESSURIZATION TEST To determine the capability of the clean room system and to maintain the specified pressure differential All doors into the clean room and the reference areas were closed throughout the duration of the test The differential pressure between the clean room and the adjacent room is measured and recorded with the micromanometer Acceptance criteria: Grade A Pressure Differential (Pa) LFC(N/A) Isolator >15 B >10 C >10 D >10

48 TEMPERATURE & HUMIDITY To determine the capability of the cleanroom Air Handling System to maintain the air temperature and relative humidity within specified limits Instrument used: Electronic Micromanometer Air conditioning system was operated continuously for at least 12 hours prior to the commencement of the test

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50 AIRFLOW VELOCITY To determine the average airflow velocity and uniformity (laminarity) To determine the air supply volumetric flow rate Instrument use: electronic micromanometer Acceptance criteria for air velocity from HEPA: 0.45 m/s ± 20% for horizontal laminar flow 0.30 m/s ± 20% for vertical laminar flow

51 AIR FLOW PATTERN TEST

52 MONITORING ACTIVITY

53 DAILY MONITORING Regular monitoring of the environment, process and finished product is an essential part of the quality assurance of all sterile prepared products. Critical parameters to be monitored daily are: Pressure across HEPA filter Temperature Humidity Glove integrity check

54 PRESSURE ACROSS HEPA FILTER Uses pressure gauge Take note of the reading at first installation If the pressure increases more than inch of water, the HEPA filter is blocked Must be documented

55 MICROBIAL MONITORING Includes airborne microbial monitoring as well as surface monitoring Conducted by using: Air sampler Settle plate Contact plate Should be done during operation

56 MICROBIAL MONITORING Media usually used for bacteria: Tryptic Soy Agar (TSA) and incubated at 35 0 C, 48 hrs Media usually used for fungi: Saboraud Dextrose Agar (SDA) and incubated at 25 0 C, 5 days

57 MICROBIAL MONITORING Acceptance Criteria: Grade Recommended limits for microbial contamination (during operation) Airsample (cfu/m 3 ) Settle Plates cfu/4hr (dia55 mm) Contact Plates cfu/plate (dia90 mm) PIC/S GUIDE TO GOOD PRACTICES FOR THE PREPARATION OF MEDICINAL PRODUCTS IN HEALTHCARE ESTABLISHMENTS; PE 010-3;1 ST October 2008) Glove print 5 fingers (cfu/glove) A <1 <1 <1 <1 B C D

58 DAILY MONITORING

59 DAILY MONITORING Action to be taken? Delay production? Inform the Responsible Pharmacist Inform HSS (get the report number)

60 DAILY MONITORING A B

61 DAILY MONITORING Action to be taken? A Delay production? B Delay production? A & B Inform the Responsible Pharmacist Inform HSS (get the report number)

62 THANK YOU