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Paul Richards CRB Consulting Engineers

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Presentation on theme: "Paul Richards CRB Consulting Engineers"— Presentation transcript:

1 Paul Richards CRB Consulting Engineers
Risk-MaPP A cGMP Driver for Contained Equipment and Facility Design Risk-Based Manufacture of Pharmaceutical Products Paul Richards CRB Consulting Engineers PharmaForum Portland, OR

2 Who am I? I am not an Industrial Hygienist
I am a Chemical Engineer who is PASSIONATE about containment Senior Process Engineer for CRB Consulting Engineers 23+ years in chemical and pharmaceutical industries Formerly Sr. Principal Engineer with Pfizer (11+ years) Extensive capital project experience in API and OSD manufacturing facilities Designed, installed, and tested many successful containment systems Steering Committee - ISPE Containment CoP Board of Directors – ISPE New England Chapter BS Chemical Engineering / MS Management PharmaForum Portland, OR

3 Topics of Discussion What is Risk-MaPP
How Risk-MaPP relates to Containment Practical solutions PharmaForum Portland, OR

4 What is Risk-MaPP? A guide to managing risks associated with cross contamination ISPE Baseline Pharmaceutical Engineering Guide Rolled out in Fall of 2010 Six years in development FDA and EMA reviewed and approved “meant to assist pharmaceutical manufacturers in the design and construction of new and renovated facilities that are required to comply with the requirements of the US FDA.” PharmaForum Portland, OR

5 Intent of Risk-MaPP Risk-MaPP provides a scientific risk-based approach, based on ICH Q9, to manage the risk of cross contamination in order to achieve and maintain an appropriate balance between product quality and operator safety. Focus on science based risk analysis to design and operation versus emotional reactions PharmaForum Portland, OR

6 cGMP Focus of Risk-MaPP
Protecting the PATIENT through quality systems to manage the risk of cross contamination PharmaForum Portland, OR

7 FDA Focus on Sound Risk Assessments
PharmaForum Portland, OR

8 Exposure Routes Mix-up Equipment Retention / Residue Carryover
Cross contamination by using wrong API, excipients, product contact materials, equipment, etc… Equipment Retention / Residue Carryover Material that remains in product contact after cleaning due to failure or inadequate cleaning Mechanical Transfer Particulate transfer on clothing/feet from operators and equipment alternating between 2 or more processing areas Airborne Transfer Cross contamination via airborne migration of particulates PharmaForum Portland, OR

9 Proper Control is Critical
PharmaForum Portland, OR

10 Risk-MaPP and Containment
cGMP versus Industrial Hygiene Patient versus the Operator Different exposure routes / pathways IH monitoring targeted at worker exposure not cross contamination How do you meaningfully correlate IH data from an air sampling pump and filter? How do you validate containment if it is a cGMP control? PharmaForum Portland, OR

11 The Relationship Exists between cGMP and Containment
Sterile Manufacturing RABS Isolators Highly hazardous (potent) compounds Containment is effective to protect workers as well as to reduce risks of cross contamination via mechanical transfer or airborne transfer PharmaForum Portland, OR

12 Reducing the Risk of Cross Contamination from Mix-up
Redundant electronic verification of materials Redundant manual checks Color coding Bar coding and RFID of materials & equipment Locked cages to store APIs with chain of custody Transfer and utility connect technologies that are unique to the process Process Analytical Technologies (ie. NIR) Separate dispensary areas Separate raw material staging areas PharmaForum Portland, OR

13 Reducing the Risk of Cross Contamination from Residue Carryover
Clean to set limits Base limits on science, risk assessment, statistical analysis Cleaning validation Equipment designed for CIP On-line monitoring / PAT Disposable product contact parts Dedicated product contact parts PharmaForum Portland, OR

14 Health Based Cleaning Limit
PharmaForum Portland, OR

15 Reducing the Risk of Cross Contamination from Mechanical Transfer
Limit transfer of compounds between suites ie. High Shear Granulation, Milling, and Drying in same suite Segregate work areas to a single product Contain at the Source Close process systems Room airflow Airlocks Gowning procedures Wipe down protocols for mobile equipment Clean mobile equipment in processing room Misting showers Cleaning bays with dirty / clean pass through PharmaForum Portland, OR

16 Reducing the Risk of Cross Contamination from Airborne Transfer
Contain at the Source Close process systems Room airflow Airlock separation to corridor Gowning procedures Wipe down protocols Misting showers Room differential pressures High room air change rates PharmaForum Portland, OR

17 Containment Design 101 Contain at the source
Avoid technique dependant systems Focus on transfer systems Design below the OEL / ADE Consider ergonomics, cleaning, sampling, waste, material compatibility Provide redundancy / secondary containment Engineer out the reliance on PPE

18 Containment at the Source Dispensing
PharmaForum Portland, OR

19 Avoid Technique Dependent Systems

20 Focus on Transfer Systems The Key to Success
PharmaForum Portland, OR

21 Typical Containment Levels
OEB I OEB II OEB III OEB IV OEB V OEL (μg/m3) 10,000 1,000 100 50 10 1 0.1 0.01 Local exhaust ventilation Crossflow booth Downflow booth Cone Valve Split Butterfly Valves HicoFlex / EziDock CSV4 Split Butterfly Valves with air extraction Bag Technology Split Butterfly (Glatt SKS / Buck TC) Rapid Transfer Ports (RTPs)

22 Rapid Transfer Ports (RTPs)
Well proven in industry Performance: < 0.1 μg/m3 Consists of an alpha (active) port attached to an isolator and a beta (passive) port connected to the portable container The beta is docked and locked to the alpha by rotation before the door can be opened Requires an isolator Vendors La Calhene Applied Containment Engineering Central Research Labs

23 Rapid Transfer Ports (RTPs)

24 Rapid Transfer Port Demo

25 Rapid Access Port (RAP)
Same basic technology at RTP, but passive attaches to equipment Active fitted with a purpose made glove bag Active made in HDPE to keep light weight Passive flange or bolted Adapt passive with sight glass Pressure cap provides 6 bar-g design Active $12,000 Passive $ 6,000 (SS) Vendor – Heaton Green Containment

26 Rapid Access Port (RAP)

27 Split Butterfly Valves
Primary Vendors GEA Buck Valve Charge Point Glatt Andocksysteme Types of Split Butterfly Valves Standard With air extraction shroud Air or Liquid Wash systems Pressure rated or not Primary concern with split butterfly valves! material on the faces of the valves after undocking

28 Split Butterfly Valves

29 Split Butterfly Valve Demo
PharmaForum Portland, OR

30 Flexible Solutions to Reduce Risk
PharmaForum Portland, OR

31 Risk Assessment Failure Modes Effect Analysis (FMEA)
Perform risk assessment to identify steps and controls, prioritize level of risk, and determine corrective actions FMEA format for risk assessment Severity – the impact on the patient Occurrence – how often this effect takes place Detection – how easily the failure can be detected Multiply each factor for a resulting risk priority number (RPN) S x O x D = RPN Set limits for RPNs Acceptable Investigate and remedy Requires immediate attention PharmaForum Portland, OR

32 FMEA Risk Scoring Example
PharmaForum Portland, OR

33 FMEA Example PharmaForum Portland, OR

34 Summary The FDA is on board with Risk-MaPP
The regulations have not changed, but the FDA will expect all manufacturers’ to “Show us your scientifically sound assessment” to prevent cross contamination and to “justify the level of controls” There are many common engineering controls to reduce risks of potential cross contamination and operator exposure Understand and document your risks and your controls PharmaForum Portland, OR

35 Questions? PharmaForum Portland, OR

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