Containment Why and How to evaluate

Transcription

1 Containment Why and How to evaluate IDMA- APA PAC 2018 May 18 & 19 At The Club, Andheri - Mumbai Presentation by: Sasidharan S Menon Subject Matter Expert (SME) Design and Evaluation Controlled environments for Contamination Control Phone contact@sasidharanmenon.com Photos and data Courtesy Fabtec, Mumbai References : Cleanroom Management in Pharmaceuticals and Healthcare Edited by Tim Sandle and Madhu Raju Saghee

2 Fundamentals of Pharmaceutical Isolators Isolator concept had several different origins Glove boxes for containment in nuclear industry Isolators for keeping germ-free mice and other mammals in biomedical reasearch Hospital patient isolators for immune-

3 Fundamentals of Pharmaceutical Isolators Lead lined containment isolators for radiopharmaceuticals Pharmaceutical manufacturing Hospital aseptic production, processing and dispensing Followed by Isolators for sterility testing This presentation will discuss the concept, why isolators are required, applications, types, design, construction, access and transfer devices, controls and monitoring in brief.

4 Isolators - Definition Current definition as given in Pharmaceutical Isolators is A separative device as defined in ISO :2004 and used for pharmaceutical and related applications. It utilises constructional and/or aerodynamic means to enclose a controlled work space. With an important note: An Isolator is not a sterilising device Mention is made of particle free air contained within a device. HEPA filter is indicated.

5 Negative Pressure Unidirectional Flow

6 Negative Pressure Unidirectional Flow

7 Negative Pressure Non-unidirectional Flow

8 Negative Pressure Non-unidirectional Flow

9 Transfer devices, Access devices and RABS Different types of Transfer devices including simple doors, air-purged chambers and Rapid Transfer Ports are defined and classified in ISO Access devices including gauntlets, glove/sleeves systems and remote controlled robotic devices are also described in Restricted Access Barrier Systems (RABS) are just barriers containing gloves and gauntlets. No attempt for sealing of controlled work space.

10 Sanitisation of controlled workspace After physical and dynamic separation, pharmaceutical isolators require sanitisation of workspace and items in it and entering it. Sanitisation is reducing the number of microorganisms, to a level judged to be appropriate, by the action of an agent on their structure or metabolism. Methods: Surface decontamination using alcoholic sprays, swabs and/or gaseous fumigation.

11 Why isolation technology is required? Product protection or Contamination control Cleanrooms and open fronted unidirectional flow systems? Human beings contribute >80 % of contamination found in cleanroms Physical barrier between the process and human beings Containment or Operator protection? Toxic substances and substances of unknown toxicity Isolators minimise the risk of operator exposure

12 Key application of Isolators Non-pharmaceutical : Biomedical research (germ-free mice and other animals requiring clean air and safe control of waste products) and Nuclear engineering (glove boxes with lead shielding with or without airflow). Next slide shows some typical industrial applications Pharmaceutical: Primary and Secondary manufacturing, and Sterility testing (reducing false positive results)

13 Industrial Isolator applications

14 Hospital Isolator applications

15 FLEXIBLE FILM ISOLATORS

16 API KILO LAB ISOLATOR

17 API KILO LAB ISOLATOR (REAR VIEW)

18 FIXED TYPE REACTOR CHARGING ISOLATOR

19 FIXED TYPE REACTOR CHARGING ISOLATOR

20 PORTABLE TYPE REACTOR CHARGING ISOLATOR

21 API DISPENSING ISOLATOR

22 BLENDING & PACK OFF ISOLATOR

23 CONTAINED OSD LINE 2 KGs

24 CONTAINED OSD LINE 2 KGs

25 Isolator Design Main enclosure Flexible film Stainless steel 304 and 316L Coated mild steel Rigid plastics Windows in rigid isolators Gaskets Seals Pneumatic seals As part of sporicidal gassing cycle, it should be

26 Transfer devices Transfer devices are designed to get materials in and out of controlled space. Classified A to F in Does not imply any ranking. Type A is not inferior or superior to Type F. Both got different designs and different uses.

27

28 Type A2 relies on outward flow of air. Known as mouse hole or dynamic hole

29 Type B1 transfer device Simple chamber with two interlocked doors

30 Type B2 Similar to B1 but with gas connections

31 Type C1 Ventilated transfer chamber

32 Type C2 Ventilated Unidirectional negative pressure air going under the work space

33 Type D With 2 HEPA filters and air/gas connections

34 additional gas connection for sporicidal gassing.

35 (RTP) DPTE (Dounle Portede Transfer Etanche) HCTP (High Containment Transfer Port) etc.,

36 Access Devices Allows manipulations inside the workspace -- GLOVES

37 Access Devices Glove sizes Sleeves Accordion sleeves Cuff rings and glove changes Changing gloves Leak testing Shoulder rings Gauntlets Half suits

38 Class 1 to 4 according to the leak rates

39 TYPICAL OEL LEVEL

40 AVAILABLE CONTAINMENT TECHNOLOGY < 1 microgram/m 3 - Isolator/Barrier Containment > 50 microgram/m 3 - Down flow Booth with Workstation > 100 microgram/m 3 - Down flow Booth > 1,000 microgram/m 3 - Laminar flow Hood > 10,000 microgram/m 3 TRANSFER TECHNOLOGY Local Exhaust Hood < 1 micrograms /m 3 - Alpha/Beta System

41 AVAILABLE CONTAINMENT TECHNOLOGY 100 Microgram/M 3 - DOWN FLOW BOOTH

42 AVAILABLE CONTAINMENT TECHNOLOGY 1,000 Microgram/M 3 - LAMINAR FLOW UNITS.

43 AVAILABLE CONTAINMENT TECHNOLOGY 10,000 Microgram/M 3 - LOCAL EXHAUST HOOD

44 PRODUCT TRANSFER DEVICE < 1 Microgram /M 3 - RAPID TRANSFER PORT (RTP)

45 PRODUCT TRANSFER DEVICE 1-20 Micrograms /M 3 SPLIT FACE BUTTERFLY VALVE

46 HANDLING /MANUPULATON DEVICE ACCESS DEVICE (HALF SUIT)

47 HANDLING /MANUPULATON DEVICE ACCESS DEVICE (GLOVES)

48 HANDLING /MANUPULATON DEVICE ACCESS DEVICE (GLOVE PORTS)

49 HANDLING /MANUPULATON DEVICE ACCESS DEVICE (HALF SUIT)

50 ESSENTIAL COMPONENTS HEPAs

51 ESSENTIAL COMPONENTS

52 Validation of Isolator Systems HEPA FILTER INTEGRITY TESTING VELOCITY PROFILE AIRBORNE PARTICULATE COUNT LIGHT INTENSITY SOUND LEVEL VIBRATION LEVEL LEAK TESTING PLC LOGIC AND INTERLOCKING BIOLOGICAL VALIDATION IN CASE OF STERILE ISOLATOR BASIC DATA SHEET TO GET MINIMUM DESIRED

53

54 References with thanks..

55 ISOLATORS