Webinar. Risk Assessment Reusable Polyester and Single Use Tyvek IsoClean Cleanroom Garments Dupont

Transcription

1 Webinar Risk Assessment Reusable Polyester and Single Use Tyvek IsoClean Cleanroom Garments Dupont 15 June 2018 GOP-Innovations your Partner for Practical Training and e-learning

2 Milenko Pavičić Pharmaceutical microbiologist, consultant, trainer, coach 10 years of research experience Vrije Universiteit Amsterdam (Medical and Oral Microbiology) Intervet International B.V. (Antibiotics R&D) 20 years of production and QC experience Pharmaceutical companies (NL, B, D, F) Hospital pharmacies (NL, B) Member of the NVZA (Dutch Society of Hospital Pharmacists) work group Microbiology and Hygiene Member of the User Committee of the NWO project Rapid Micro Statistics (TU/e, Prof. E. v/d Heuvel)

3 Pavičić Pharmaceutical Microbiology and GOP-Innovations Consultancy Courses Training Practical Training E-learning Microbiology, Aseptic production, Cleanrooms, Sterilisation, Cleaning, Disinfection, cgmp, Pharmacopoeias, Annex 1, QC, Validation, Qualification, Behavior, SOPs, Media fills, Environmental monitoring, Water systems, Sampling, Hygienic Design, Contamination Risk, Biosafety, Biosecurity

4 Subjects for today s webinar Quality Risk Management (QRM) Risk assessments Risk assessment reusable polyester and single use Tyvek IsoClean cleanroom garments Results and discussion Conclusions

5 New EU-GMP Annex 1 Processes, equipment, facilities and manufacturing activities should be managed in accordance with Quality Risk Management (QRM) principles that provide a proactive means of identifying, scientifically evaluating and controlling potential risks to quality.

6 Quality Risk Management (QRM) A systematic process for the assessment, control, communication, and review of risks to the quality of medicinal product across the product lifecycle.

7 Risk Assessment A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards.

8 Harm, hazard, risk Harm: Health damage (illness, disability, death) Hazards: Medicines contaminated with micro-organisms, particles or fibers Risk: Probability of the occurence of harm and the severity of that harm

9 Cleanroom garments (1) GMP Contaminated garments may impact sterility of medicines, which is a Critical Quality Attribute Cleanroom garments form an important part of contamination control strategy

10 Cleanroom garments (2) GMP Garments shall protect the environment and medicines from contamination from people Garments shall be clean and shall not shed too many particles (qualified) and the release of fibers should be minimized (qualified) Garments shall be sterile (qualified) for grade A/B or shall have a very low (qualified) bioburden for grade C and D

11 Risk assessment cleanroom garment A risk assessment based on failure mode and effects analysis (FMEA) was executed Focus on relevant aspects of cleanroom garments that influence contamination of the garment and the cleanroom environment Comparison of reusable polyester and single use Tyvek IsoClean cleanroom garments

12 Explanation Risk Assessment qualitative risk component ranking Qualitative Ranking Risk Component Severity Occurrence Detection High Impact of the unwanted event* is severe Occurrence is often The failure will almost certainly escape detection Medium Impact of the unwanted event is moderate Occurrence is periodic Controls may detect the existence of a failure Low Impact of the unwanted event is low Occurrence is seldom The failure is obvious and readily detected *: The unwanted event is microbiological and/or particulate contamination of the gown and/or the environment leading to action limit excursions

13 Explanation Risk Assessment risk priority ranking (RPR) Detection Occurrence High Medium Low Low Medium High This cause is likely to occur, and when it does, it will be detected. Low or Medium Risk. This cause could occur, and if it did, it would be detected. Low or Medium Risk. This cause is not likely to occur, and if it does it will be detected. Low Risk. This cause is likely to occur, and the detection is not certain. High Risk. This cause could occur, and it could be detected. Medium or High Risk. This cause is not likely to occur, and if it did, it may be detected. Low or Medium Risk. This cause is likely to occur and is not likely to be detected. High Risk. This cause may occur, and it will not be detected. High Risk. This cause is not likely to occur, but if it did occur, it probably would not be detected. Medium or High Risk.

14 Risk assessment scope The influence of the different risk factors on the microbiological and particulate cleanliness of the garment itself and the working environment was evaluated Contamination with pyrogens and chemical contamination were not part of this risk assessment

15 FMEA failure (= unwanted event) Microbiological and/or particulate contamination of the gown and/or the environment leading to action limit excursions in the manufacturing cleanrooms where sterile medicines are produced, i.e. EU-GMP grade A/B and supporting C and D areas

16 FMEA impact of excursions of action limits Quality of the product or production environment is or may be at stake Action limit excursions in grade A/B may result in loss of sterility of the medicine or contamination of the medicine with an unacceptable amount of particles or fibers Severity is HIGH in case of loss of sterility

17 Risk assessment risk factors 1. Manufacturing of garment 2. Washing and sterilization 3. Garment repairs 4. Storage 5. Transport 6. Storage in warehouse 7. Transfer into cleanrooms 8. Storage in cleanroom 9. Gowning 10. Working 11. Ungowning

18 Risk assessment risk factors

19 Risk assessment risk factors

20 Risk assessment risk factors

21 Results (1)

22 Causes or process failures 1. manufacturing of the garment The risk for failure is lower for Tyvek IsoClean since the production of raw materials and garments is well controlled and done by the same manufacturer For reusable polyester garments this risk varies considerably

23 Causes or process failures 2. washing and sterilization and 3.repairs These risks are only applicable for reusable polyester garments and is not relevant for Tyvek IsoClean garments

24 Causes or process failures 4. storage in warehouse supplier The longer the storage the higher the risk for failures (damage, contamination)

25 Causes or process failures 5. transport The risk for failure is somewhat lower for Tyvek IsoClean garments because these are packed in a single-use sealed box. Most reusable garments are packed in a reusable crate with a closed lid. Packaging for DS products (Tyvek IsoClean Coverall)

26 Results (2)

27 Causes or process failures 6. storage in warehouse end-user The longer the storage the higher the risk for failures (damage, contamination)

28 Causes or process failures 7. transfer into cleanroom The risk for failure is somewhat lower for Tyvek IsoClean garments because of the package design, i.e. double sterile robust packaging which is then double clean packed. Packaging for DS products (Tyvek IsoClean Coverall)

29 Causes or process failures 8. storage in cleanroom The longer the storage the higher the risk for failures due to contaminated or damaged garment or packagings

30 Results (3)

31 Causes or process failures 9. gowning The risk for failures is mostly influenced by operator behavior, gowning method, gowning technique and the cleanliness of the environment

32 Causes or process failures 10. working (1) The risk for failures is lower for Tyvek IsoClean garments because the permeability of these garments is much lower compared to reusable garments. No risk for failures due to faulty repairs.

33 Causes or process failures 10. working (2) The quality of reusable garments will decline as a result of frequent washing and sterilization. This will lead to damage to the fabric and larger pores, thereby increasing the release of particles and fibers into the environment.

34 Causes or process failures 10. working (3) It is not known if there is a difference in pump effect between Tyvek IsoClean garments and reusable polyester garments. However, this phenomenon will play a role in contamination of the environment.

35 Causes or process failures 11. ungowning The degree of contamination of the environment is mostly influenced by the location and technique of ungowning.

36 Conclusions (1) The risk for microbiological or particulate contamination of the gown or the environment leading to action limit excursions is lower for Tyvek IsoClean garments compared to reusable polyester garments. The difference in pump effect between Tyvek IsoClean garments and reusable polyester garments should be investigated further.

37 Conclusions (2) The lower risk is mainly due to differences in the quality of raw materials and manufacturing, a closed and multiple clean and sterile packaging concept, better barrier properties (microorganisms and particles), and the single-use concept thereby eliminating the deteriorative effect of repeated use, washing and sterilization.

38 Additional applications for Tyvek IsoClean garment Tyvek IsoClean garment may also be a good candidate for people who work with cytotoxic substances, pathogenic microorganisms and viruses, other toxic substances.