Clean Room Certification Reports Interpreting and Acting on the Good, the Bad and the Ugly!

Transcription

1 Clean Room Certification Reports Interpreting and Acting on the Good, the Bad and the Ugly! Marc Stranz, PharmD, Vice President of Clinical Operations BioScrip, East Greenville, PA Jim Wagner, President Controlled Environment Testing, Hellertown, PA

2 CE Credit in Five Easy Steps! 1. Scan your badge as you enter each session. 2. Carry your Evaluation Packet to every session so you can add session evaluation forms to it. 3. Track your hours on the Statement of Session Attendance Form as you go. 4. At your last session, total the hours and sign both pages of your Statement of Session Attendance Form. Keep the PINK copy for your records. Put the YELLOW and WHITE copies in your Evaluation Packet. Make sure a completed Session Evaluation Form is in your Evaluation Packet for each session you attended. Missing one? Extras are in a file near Registration. 5. Complete the General Attendance Evaluation Form located in your Evaluation Packet and place it back in your envelope. Write your name on the outside of your Evaluation Packet envelope, seal it, and drop it in the box near Registration. Applying for Pharmacy CPE? If you have not yet registered for an NABP e Profile ID, please visit to do so before submitting your packet. You must enter your NABP e Profile ID in order to receive CE credit this year! 3/24/2014 2

3 Disclosure Slide Jim Wagner is a consultant. Conflict of interest was resolved by peer review of slide content. Marc Stranz declares no conflicts of interest or financial interest in any service or product mentioned in this program. Clinical trials and off label/investigational uses will not be discussed during this presentation. 3/24/2014 3

4 Overview of CAG 008

5 CAG Certification Matrix for Sterile Compounding Facilities Initial Publication Date 2010 Latest update January 31, 2012

6 CAG Certification Matrix for Sterile Compounding Facilities Currently Secondary Engineering Controls ONLY Primary engineering controls section being developed Say what you are going to do and document everything you did What is the objective of the engineering control? How do I prove it does that? Good certification documentation practice

7 CAG 008 (page 1/11) The following table provides a matrix for reviewing the certification of secondary engineering controls (cleanrooms) used in sterile compounding facilities designed to comply with USP chapter <797>. The Controlled Environment Testing Association has developed the applications guide, CAG (2012), which is referenced in chapter <797>. The table assumes the certification professional follows this applications guide for general guidance. The certifier should provide specific details of each test conducted either directly in the certification report or in a Standard Operating Procedure (SOP) referenced in the certification report. All calculations including intermediate values should be documented on the certification report. Calibration certificates should be provided for every test instrument used and the specific model number and serial number of each test instrument should be documented on the certification report. The certification report should include the name and address of the testing agency, the name and qualifications of the certification technician (including accreditations), the name and version of any referenced standards, and a clear identification of the physical location of the equipment being tested.

8 CAG 008 (page 1/11) The actual acceptance criteria for each test should be agreed to between the owner and certifier based on industry guidance. Good documentation practices include stating an acceptance range for each test. The acceptance values listed in this document are customary and standard for cleanrooms. Where no criteria exist, those used for FDA aseptic drug manufacturing have been used.

9 CAG 008 Every certification report should include: Statement of the occupancy state (at rest, as built, or operational [dynamic operating conditions]). Particle count survey Smoke pattern test Environmental Sampling (not covered in 008) A statement of pass or fail should be clearly made for every test

10 CAG 008 (page 1/11) This review does not include the viable environmental sampling (See CAG for guidance on environmental monitoring). It is limited to the engineering control performance verification (certification) procedures covered in the CETA document as referenced in chapter <797>. The control points of interest are: Assuring adequate HEPA filtered air supplied to the rooms and proper airflow velocities in unidirectional cleanroom spaces (airflow testing) Assuring separation from rooms of different cleanliness classification and purpose (differential pressure and displacement airflow) Assuring that the HEPA filters are leak free (HEPA filter integrity test) Providing visual verification that air flows from clean to less clean areas and that unidirectional airflow areas are free from turbulence and reverse flows (airflow smoke pattern test) Assuring that the design when operating properly yields the intended cleanliness classification under dynamic operating conditions (particle count test) Assuring the temperature within the compounding facility is appropriate for sterile compounding (temperature testing) Assuring the humidity within the compounding facility is appropriate for sterile compounding (humidity testing)

11 Item Basis for compliance Minimum reported values Test equipment requirement Airflow (Non Hazardous Compounding Non hazardous sterile compounding rooms must maintain a minimum of 30 Air Volume through each supply HEPA filter CFM. rooms) total HEPA filtered Air Changes Total HEPA Filtered air volume (1) Per Hour (ACPH). supplied to the room CFM. At least 15 HEPA filtered ACPH must come from air sources outside the room(e.g. HVAC, Fan Filter Units, recirculation system, etc.) Up to half of the total HEPA filtered air can be generated by the recirculated primary engineering control. The minimum ACPH requirement for an ISO class 8 ante area is not specified in USP <797>. A minimum of 20 ACPH is commonly referred to by the FDA and others. Total HEPA filtered air volume added to the room total from the PEC CFM. Room volume Ft 3. Dimensions used to calculate the room volume inches. If the primary engineering control is used for a portion of the minimum 30 total ACPH, specific calculations for this source should be documented. All calculations along with the total HEPA filtered room ACPH should be documented. The preferred test equipment is the airflow capture hood used to measure directly in airflow volume (CFM). When this method cannot be employed a secondary method may be used. The alternative methods may include thermal anemometers for velocity measurements. Maximum recommended calibration interval 12 months for electronic capture hoods 6 months for thermal anemometers.

12 CAG Airflow Velocities in an ISO class 7 buffer area (and ISO Class 7/8 ante areas) page 3/11 Minimum documentation required Air Volume through each supply HEPA filter CFM Total air volume supplied to the room CFM Room volume Ft 3 Dimensions used to calculate the room volume inches All calculations along with the total HEPA filtered room ACPH should be documented. Preferred test equipment Airflow capture hood used to measure directly in airflow volume (CFM)» A thermal anemometer may be used when a capture hood does not fit in the given space.

13 Item Basis for compliance Minimum reported values Test equipment requirement Airflow (Velocities in a unidirectional zone) (1) Some sterile compounding facilities integrate a Vertical Laminar Flow (VLF) area directly into the cleanroom design. This area is typically segregated from the ISO Class 7 buffer area in which it is placed with Lexan shields. On rare occasions, the entire buffer area can be classified as an ISO class 5 unidirectional space. USP does not specify a velocity range but does require the primary engineering control to be unidirectional and to verify that the air sweeps over and away from the product under dynamic operating conditions. A velocity profile across the entrance plane into the work area is required to establish and prove maintenance of a state of control over this critical space. The actual acceptable velocity range should be confirmed with an airflow smoke pattern test (see #4). Most VLF spaces operate at an entrance plane velocity of between fpm. The entrance plane is typically 6 below the HEPA filter or diffuser. Individual velocity readings displayed on a grid corresponding to reading locations in FPM Average velocity through the entrance plane to the work area in average FPM. Listing of the acceptable velocity range as validated with smoke pattern testing. A statement of pass or fail The preferred test equipment is the thermal anemometer or an electronic manometer with a multipoint tube array Maximum initial recommended calibration interval 12 months for thermal anemometers 6 months for electronic capture hoods

14 CAG Airflow Velocities in a unidirectional zone page 4/11 ISO Class 5 cleanroom ISO Class 5 zone within an ISO Class 7 buffer area Minimum documentation required Individual velocity readings on a grid corresponding to reading locations in FPM Average velocity through the entrance plane in FPM Listing of the acceptable velocity range as validated with smoke pattern testing Preferred test equipment Thermal anemometer or electronic manometer with multipoint tube array

15 Summary Certification reports should clearly identify what is being done with a very general description of how it is being done. The report should include all data collected, calculations, assumptions, clear identification of sample locations, occupancy state, and a statement of overall pass or fail along with pass fail statements for every test.

16 Retrofitting a Pharmacy Cleanroom Marc Stranz, PharmD Vice President, Clinical Operations Bioscrip

17 Outline Why remodel the cleanroom? What are the alternatives? Construction, installation, testing Timeline Construction issues 3/24/

18 The old cleanroom No biohazard compounding room Five laminar hoods reaching end of useful life Not enough compounding room space Issues maintaining particle counts and viable particles due to space limitations and curtain wall 3/24/

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20 Situation Cannot shut down existing cleanroom Remodel cleanroom Limited adjacent expansion space No alternate compounding site during construction Relocate room Space available proximate to warehouse 3/24/

21 Decisions ISO 7 cleanroom with LF hoods ISO 6 cleanroom with ISO 5 bench space Use plenum or direct connect filtration Drywall, modular, or combined cleanroom 3/24/

22 Remodel existing cleanroom Replace five 6 laminar hoods Expand compounding room Add biohazard room to expand services Increase HVAC and filtration Change curtain wall to hard wall Estimate $163,211 3/24/

23 Build new cleanroom Facility (design, permit, drywall, HVAC, plumbing, flooring, electrical, paint, seismic) Cleanroom and furnishings Estimate $156,000 3/24/

24 Timeline for new cleanroom Plans Construction contract Permits Construction Cleanroom/Certification Certificate of Occupancy 14 days 14 days 21 days 60 days 7 days 116 days 3/24/

25 Cleanroom design 3/24/

26 Plenum based cleanroom 3/24/

27 Direct duct based cleanroom 3/24/

28 HEPA filtration Passive filtration remote blower controls air velocity through the filter Active filtration fan controls the air velocity of the air through the HEPA filter 3/24/

29 Air flow characteristics Low wall returns reduce entrainment and reflux of air into the ISO 5 space 3/24/

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33 Discussion/questions? 3/24/