Upload
others
View
3
Download
0
Embed Size (px)
Citation preview
Slide 1 © PharmOut 2017
Defining, achieving, and demonstrating effective performance of containment systems
Gordon Farquharson, July 2017
Slide 2 © PharmOut 2017
Agenda
• Objectives and Principles.
• A hierarchy of containment techniques.
• Basis of Design & Selection.
• Proving the performance – Safety Qualification.
• Maintaining safe operation.
• Things that can go wrong!
Objectives and Principles
Slide 4 © PharmOut 2017
What are we trying to achieve?
• Occupational health & safety containment of radiological, potent, toxic or biologically hazardous compounds and materials.
• Cross-contamination control.
• Minimise contaminated space/volume/surfaces.
Slide 5 © PharmOut 2017
Occupational Health & Environmental Protection approach
• Identify the hazardous agent.
• If possible use something less hazardous (Eliminate the hazard).
• Contain the hazard in a closed process, and consider failure mode (might require a secondary containment).
• Contain an open process is a containment.
• Use personal protective equipment alone as a final resort.
Slide 6 © PharmOut 2017
What influences containment performance?
• The inherent capability of the system being employed – How to define this is a challenge.
• The source strength of challenge to the system.
• The duration of the challenge event.
• Different phases of the operational cycle of a device:
• Connect
• Disconnect
• Cleaning
• Failure mode
Slide 7 © PharmOut 2017
Practicalities of containment engineering
• Difficult to engineer a device with a specific level of containment capability.
• For practical reasons, we use the following approach:
• Usually select a standard or adapted device that meets broad objectives.
• Develop design principles – + usually explore some options.
• GMP and Safety Case review, including failure modes.
• Tender and procure.
• FAT, often including functional and containment testing.
• Install and commission.
• Quality and Safety Qualification.
• Start normal operations.
Slide 8 © PharmOut 2017
A Typical Hierarchy For Containment This Graphic Is Reproduced Courtesy Of Extract Technology Ltd.
Gordon’s Containment Hierarchy
Slide 10 © PharmOut 2017
Reduce the hazard
• Not possible to remove the hazardous agent.
• Handling a liquid solution or slurry generally has lower risk of exposure than powder.
• Consider doing this during dispensing of a potent API.
Slide 11 © PharmOut 2017
Use of open fronted MBSC or Specialised Cytotoxic Safety Cabinets
Containment level 3
• Containment
relies upon
effective air
inflow.
• Containment
performance 3-5
log reduction
source
outside.
• Remember
cleaning & Filter
testing and
replacement.
Slide 12 © PharmOut 2017
Downflow Booth (Typical arrangement)
Slide 13 © PharmOut 2017
Downflow Booth (Enhanced with barriers)
Slide 14 © PharmOut 2017
Cross Flow B Dispensary : Better material handling
Slide 15 © PharmOut 2017
Think through the manual handling as well
Slide 16 © PharmOut 2017
Booth issue – Work practice can destroy the benefit and protection
Airflow Direction
Contamination across operator breathing zone
Slide 17 © PharmOut 2017
Personal Monitoring Equipment
Sanofi –Aventis Compiegne. Industrial Hygiene Sampling and Remedial actions
Gravimetric and Real-Time dust
monitors for personnel and
environments
Slide 18 © PharmOut 2017
Dust monitoring instruments develop
Slide 19 © PharmOut 2017
Charging Potent Drugs
Cup Hermann
Slide 20 © PharmOut 2017
Charging Potent Drugs
Cup Herman™ by Bio-Components
Switzerland
Slide 21 © PharmOut 2017
Split Butterfly Valve
Slide 22 © PharmOut 2017
22
GLATT valve
Air:
< 10 µ/m³
Wipe:
2-3 mg/m³ (1 transfer)
2-3 mg/m³ (5 transfers)
Split Butterfly Valves:
PSL valve
Air:
< 5 µ/m³
Wipe:
5-15 mg/m³ (1 transfer)
25-32 mg/m³ (5 transfers)
BUCK valve
Air:
< 5 µ/m³
Wipe:
5-15 mg/m³ (1 transfer)
20-30 mg/m³ (5 transfers)
Slide 23 © PharmOut 2017
Chargepoint Technology “Pharmsafe” split butterfly valve with extraction.
Slide 24 © PharmOut 2017
24
Cone Discharge + Docking Valve
Photograph courtesy of Matcon Ltd
Slide 25 © PharmOut 2017
Split butterfly valves in action
• Contained connections
• Make sure that failure modes are considered.
• Alignment of split butterfly valves and be critical.
• FAT and SAT essential.
In particular, ensure excessive deflection of hoist is engineered out.
Slide 26 © PharmOut 2017
Potent Compound Dispensing1. Downflow principle 2. Local Containment
Range 1 to 0.1 microg/cu.m
Range 10 to 1 microg/cu.m
Slide 27 © PharmOut 2017
Glovebag systems in R & D
Slide 28 © PharmOut 2017
Weighing Dispensing Isolator
Slide 29 © PharmOut 2017
Automated Solution: Easier to use – minimal operator interface = low dust exposure
Slide 30 © PharmOut 2017
Complete Small batch System:
Sub-division Isolator
Poly bottles in 3 sizes
Microcharge Vessel Loading Unit
BULK SUB-DIVISION INTO BATCH SIZES:
Slide 31 © PharmOut 2017
RTP PORTS AND CONTAINERS
Interchangeable with other RTP/DPTE Devices
Nanogram level transfer technology
Slide 32 © PharmOut 2017
Large Scale Filter Dryer off-load isolator –Continuous Liner
Slide 33 © PharmOut 2017
Reactor charging isolator
Image courtesy of
PSL, Powder Systems
Ltd.
ASSESSING PHARMACEUTICALCONTAINMENT EQUIPMENT USINGSURROGATE MONITORINGValidation of containment performance
Based on the ISPE SMEPAC initiative
Slide 35 © PharmOut 2017
www.ispe.org
Slide 36 © PharmOut 2017
Applied to large Booths
Define a known source challenge of airborne particles inside.
Determine what percentage gets out!
This is a measure
Slide 37 © PharmOut 2017
Applied to small enclosures
Slide 38 © PharmOut 2017
Applied to bespoke isolators
Slide 39 © PharmOut 2017
Simple explanation of surrogate monitoring
• Handling or processing lactose or another surrogate material in containment equipment such as an isolator, material transfer valve or other equipment intended to contain active pharmaceutical ingredients (APIs).
• Conducting air sampling and surface sampling to determine how much dust escapes from the containment.
• The sampling results provide a means of estimating how effectively the equipment will contain the API under similar conditions of use.
Slide 40 © PharmOut 2017
Purpose and benefits
• Evaluate containment performance without potential exposures to potent Active Pharmaceutical Ingredients (APIs)
• Evaluate containment performance in situations where an analytical method has not been developed for the API of interest
• Evaluate equipment/devices before purchase
• Obtain baseline data to compare equipment models from different suppliers
• Obtain baseline data to compare different technologies
• Evaluate performance of new equipment before initial production begins using potent API
• Retest to determine if performance of existing equipment has degraded over time versus the baseline
Slide 41 © PharmOut 2017
Some limitations of surrogate testing
• Does not evaluate exposures to gases or vapours which may escape the containment
• Results not directly comparable to materials with different physical properties
• Results do not guarantee compliance with OELs established for specific APIs
Slide 42 © PharmOut 2017
Example of contained dust collection system tested
Dust Collection System designed for bag-in/bag-out filter changing and collection drum liner removal
Slide 43 © PharmOut 2017
Surrogate materials
Lactose
• Flow characteristics
• Analytical limit of detection
• Low toxicity
• Availability
• Low cost of surrogate
• Cost of sample analysis
• Solubility
Other surrogates to consider
• Naproxen Sodium
• Riboflavin (vitamin B2)
• Mannitol
• Sucrose
• Acetaminophen (paracetamol)
Slide 44 © PharmOut 2017
Surface wipe & Swab Samples
(c) Critical Systems 2011
21/07/2017
Slide 45 © PharmOut 2017
Sampling strategy
Prevent ingress of any contamination likely to bling the study.
Background air and surface samples should be taken.
Take human breathing zone samples.
• Long term, and
• Short term (event or task based).
Take general air samples.
• Long and short term.
• At critical points of actual or potential leakage.
Surface wipe or swab samples at critical locations.
Slide 46 © PharmOut 2017
Example of general air samples
Sample location around a split butterfly valve
(c) Critical Systems 2011
21/07/2017
Slide 47 © PharmOut 2017
Surface samples
Collect after individual process cycles or steps
Collect at end of overall operation
Slide 48 © PharmOut 2017
Surface test results
Pharmaceutical companies may or may not have established limit for surface contamination for specific APIs.
Often detect contamination where air samples were below detection.
May show need for additional cleaning before removing objects from containment or to other areas (e.g. clean contaminated RTP seal when container is undocked).
(c) Critical Systems 2011
21/07/2017
Slide 49 © PharmOut 2017
Summary
• Surrogate monitoring evaluates the effectiveness of containment equipment using materials having low toxicity.
• Lactose is the recommended surrogate material, but others may also be used.
• The sampling strategy includes both air samples and surface samples.
• The results can be helpful in selecting containment equipment: Vendor produces data to support sale proposal.
• Testing can be part of safety qualification of a system; and can support a multi-product, non dedicated facility design. There are limitations. Therefore, exposure to the actual API should also be evaluated once the containment becomes operational in the lab or production setting.
Slide 50 © PharmOut 2017
Thank you for your time.Questions?
Gordon Farquharson
www.pharmout.net
Executive Consultant
Slide 51 © PharmOut 2017
This presentation and all associated materials are copyrighted and all rights reserved by PharmOut.
No part of this presentation may be reproduced or transmitted in any form or for any purpose without the express permission of PharmOut in writing. The information contained herein may be changed without prior notice.
Data contained in this presentation serves informational purposes only.
PharmOut does not warrant the accuracy or completeness of the information, text, graphics, links, or other items contained within this presentation. This presentation is provided without a warranty of any kind, either express or implied, including but not limited to the implied warranties of merchantability, fitness for a particular purpose, or non-infringement.
PharmOut shall have no liability for damages of any kind including without limitation direct, special, indirect, or consequential damages that may result from the use of this presentation.
©PharmOut Copyright Notice - 2017All rights reserved