Glove Management PDA Ireland Chapter Dublin 04 th Oct 2018 Dr. Aidan Harrington DPS Group
Agenda Regulatory Requirements Glove Integrity & Contamination Control Current Practices for Glove Management Benchmarking Data 2
Gloves and Regulations act as if gloves are contaminated PICS PI-014-3 Isolators used for Aseptic Processing and Sterility Testing Isolators / RABS 3
Gloves and Regulations Isolator gloves were creased Isolator gloves lying against product bags MHRA GMP Inspection Deficiency Trend Data 2016 4
Gloves and Regulations When inspecting a RABS: Determine that the gloves and gauntlets attached to the glove ports are sterile when installed FDA Compliance Program & Guidance Manual: Sterile Drug Product Inspections Sept 2015 5
Gloves and Regulations Integrity testing of the barrier systems and leak testing of the isolator and the glove system should be performed using visual, mechanical and physical methods. Annex 1 A program to minimize the risk of loss of integrity of gloves, sleeves and suits should be present PICS A faulty glove or sleeve assembly represents a route of contamination and a critical breach of isolator integrity - FDA 6
Glove Integrity Checks Primarily pressure decay and visual ISO 14644-7 Hole diameter of 38 62 µm (2017 Skan WGT Qualification) 7
PDA Aseptic Processing Survey 2017 What method(s) do you use to detect holes or integrity test the gloves? 8
Leak testing The opening diameter was rechecked at Bosch FeW with a Microskop, type Mycrona Altera Nano JML 2 P52 Nr.1 Objektive 10:1. The measured diameter is slightly smaller: 97 µm instead 100 µm as specified. 9
Leak Testing Source: Yves Scholler, Skan AG: ISPE Presentation, Risk of Contamination Through Pinholes in Gloves and How to Prove the Integrity. 2015 10
Gloves and Regulations Microbiological tests are used to supplement or substitute physical tests USP 1208 Sterility Testing Validation of Isolator Systems 11
Gloves and Regulations Note: Standard finger dab plates may not be sensitive enough to detect low levels of contamination Imersion of the gloves in 0.1% peptone water followed by filtration of the diluent and plating on growth media can detect loss of integrity in the gloves that would otherwise go unnoticed USP 1208 Sterility Testing Validation of Isolator Systems. 12
Pinhole Risk How Risky are Pinholes in Gloves? A Rational Appeal for the Integrity of Gloves for Isolators Gessler, A. ; Stark, A.; Sigwarth, S. & Moirandt, C. PDA J. Pharm Sci and Tech 2011 65: 227-241 13
Pinhole Risk - Summary To evaluate the potential risk of microbial migration through glove pinholes Preparation of gloves with a realistic bioload Established that microorganisms successfully migrate through pinholes Realistic bioloads do not pose a risk based in the pinhole sizes tested (100-290µm) 14
Pinhole Risk - Impact of Momemtary Pressurisation Impact: Glove entry and exit procedures Source: Drinkwater, J.L and C. Maier, Oct 2016, European Pharmaceutical Review: Isolators and RABS Glove Management in Bio-Decontamination Risk Management. 15
Pinhole Risk Venturi Effect ISO 14644-7 Section 9.4 Leak Testing Devices that use overpressure or flow may be at risk of induction leakage when operating under transient volume changes such as glove entry or withdrawl. 16
PDA Aseptic Processing Survey 2017 How often do you see glove integrity test failures? 17
PDA Aseptic Processing Survey 2017 If your firm uses isolators for aseptic processing, how frequently do you integrity test gloves? Please check all that apply. 18
Annex 1 Draft Integrity testing..should be performed at defined periods, at a minimum at the beginning and end of each batch, and following any intervention that may affect the integrity of the unit. Interpreted as: Visual inspection of gloves prior to and post all interventions 19
PDA Aseptic Processing Survey 2017 If gloves fail integrity test, what is your firm s response? Please check all that apply. 20
SCAN Benchmarking 2014* Do you ever re test if the automatic glove tester fails? Site 1 Site 2 Site 3 Site 4 Site 5 Site 6 Site 7 No x x Yes X 3x max X 1x max x x Glove Leak Testing in RABS & Isolators: A Foundation for Reasonable Testing and Good Practices for Risk Mitigation. Lee Edwards, Skan, 2014 21
Advanced Aseptic Processing In relation to glove integrity testing not all failed or aborted results were adequately documented within the batch documentation. There were examples of failed or edge of failure glove integrity tests which had not been adequately investigated HPRA Open Day Feb 2017 22
SCAN Benchmarking 2014* What is the trigger to change the glove? Site 1 Site 2 Site 3 Site 4 Site 5 Site 6 Site 7 Time X 12 weeks X X 1 month X X twice a year Number of cycles Hole/leak X X X X X Glove Leak Testing in RABS & Isolators: A Foundation for Reasonable Testing and Good Practices for Risk Mitigation. Lee Edwards, Skan, 2014 23
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Conclusion Key Considerations re Glove Management RABS vs Isolator gloves (requirement for sterilization of RABS gloves?) Routine cleaning and disinfection Where gloves are located versus critical activities impact on response to integrity failure. Visual testing pre-post all interventions Bioburden control on the outside sterile gloves Dr. Aidan Harrington Principal Consultant DPS Group www.@dpsgroupglobal.com Glove EM risk based Clearly defined procedural control for glove entry and exit 25