Ce diaporama a bien été signalé.
Nous utilisons votre profil LinkedIn et vos données d’activité pour vous proposer des publicités personnalisées et pertinentes. Vous pouvez changer vos préférences de publicités à tout moment.
Comparison of Surrogate and API Exposure
Monitoring Results at a
Pharmaceutical Industry in China
Shaobo Chen, Senior Indu...
Agenda
• Background
• Objectives of Study
• Methods and Evaluation Criteria
• Monitored Unit Operations
• Results
• Recomm...
Background
Surrogate monitoring has been widely used as a substitute for
air sampling of Active Pharmaceutical Ingredients...
Background
Advantages:
• Relatively low toxicity of the surrogate compounds
• Sensitive limit of detection
• Considered ef...
Objectives of Study
• To identify personal breathing zone exposure to surrogate
and APIs for the same unit operations.
• T...
Methods
• Mannitol was chosen as surrogate – Limit of Quantitation
(LOQ) of 1 nanogram, which was more sensitive than that...
Evaluation Criteria
• The company recommended eight-hour OEL-TWA of 5 µg/m3
and Surface Guidance Value (SGV) of 5 μg/100 c...
Monitored Unit Operations
Monitored Unit Operations:
• QC Sampling
• Dispensing and Pre-blending
• Excipient charging and ...
Changes Between Surrogate and API
Monitoring
• QC Sampling
Work Practices - The operator performed cleaning after API
samp...
Changes Between Surrogate and API
Monitoring
• Excipient charging and blending
Work practices
Sampling duration – 7 min an...
Results
11
• QC Sampling with Glove Box
Surrogate (µg/m3) API (µg/m3)
Personal < 0.0279 10.8
Between the glove ports < 0.0...
Results
12
• Dispensing and Pre-blending
Surrogate (µg/m3) API (µg/m3)
Primary Operator 0.0686 < 0.0171 < 3.75 < 1.25 < 1....
Results
13
• Charging Excipient into IBC Which Contained Surrogate or API
Surrogate (µg/m3) API (µg/m3)
Primary Operator 3...
Results
14
• Compression
Surrogate (µg/m3) API (µg/m3)
Operator 1 0.57 0.173 2.91 0.922 3.54
Operator 2 0.121 0.0632 < 0.7...
Results
15
• Corridor Air Samples and Wipe Samples for API (Partial)
Wipe samples Range (µg/100 cm2)
On the handle inside ...
Recommendations to reduce
exposures
• Evaluate feasibility of providing in-situ cleaning of the glove box used for
QC samp...
Recommendations to reduce spread
of API Contamination
• Define Red Zone (potentially contaminated area such as API handlin...
Lesson Learnt
• Surrogate monitoring is indicative and not confirmative of the API
particulate containment and exposures.
...
Thanks you.
Any questions?
Shaobo Chen, Senior Industrial Hygienist
Bob.chen@issehs.com
19
Vous avez terminé ce document.
Télécharger et lire hors ligne.
Prochain SlideShare
What to Upload to SlideShare
Suivant
Prochain SlideShare
What to Upload to SlideShare
Suivant
Télécharger pour lire hors ligne et voir en mode plein écran

Partager

Presentation ai hce 2017 bob chen updated-3.0

Télécharger pour lire hors ligne

Presentation ai hce 2017 bob chen updated-3.0

Livres associés

Gratuit avec un essai de 30 jours de Scribd

Tout voir

Livres audio associés

Gratuit avec un essai de 30 jours de Scribd

Tout voir
  • Soyez le premier à aimer ceci

Presentation ai hce 2017 bob chen updated-3.0

  1. 1. Comparison of Surrogate and API Exposure Monitoring Results at a Pharmaceutical Industry in China Shaobo Chen, Senior Industrial Hygienist International Safety Systems, Inc. (ISS) China www.issehs.com
  2. 2. Agenda • Background • Objectives of Study • Methods and Evaluation Criteria • Monitored Unit Operations • Results • Recommendations • Lesson Learnt 2
  3. 3. Background Surrogate monitoring has been widely used as a substitute for air sampling of Active Pharmaceutical Ingredients (APIs) to determine particulate containment efficiency and employee exposures. Common Surrogate used are: • Lactose • Naproxen sodium • Mannitol • Acetaminophen • Sucrose 3
  4. 4. Background Advantages: • Relatively low toxicity of the surrogate compounds • Sensitive limit of detection • Considered effective when validated API sampling and analytical method are not available • Considered effective to determine particulate containment efficiencies before API manufacturing begins 4 Disadvantages: • Surrogate monitoring results may not be representative of API particulate containment and exposures due to variabilities in surrogate – API properties and work practices • API exposure monitoring may not be done based on acceptable surrogate monitoring results
  5. 5. Objectives of Study • To identify personal breathing zone exposure to surrogate and APIs for the same unit operations. • To assess the particulate containment performance of equipment. • To assess the risk of contaminant spreading. • To verify how best the surrogate monitoring result represents API particulate containment and exposures. 5
  6. 6. Methods • Mannitol was chosen as surrogate – Limit of Quantitation (LOQ) of 1 nanogram, which was more sensitive than that of API. • The actual API (Occupational Exposure Band (OEB) 4) – LOQ of 0.6 micrograms. • Active air sampling pumps were used as monitoring device. • 25mm 1 micron Teflon® filters loaded into cassettes and IOM samplers were used for the Mannitol and API sampling, respectively. Sampling flow rates were approximately 2 L/min. • AIHA accredited laboratory analyzed the samples. 6
  7. 7. Evaluation Criteria • The company recommended eight-hour OEL-TWA of 5 µg/m3 and Surface Guidance Value (SGV) of 5 μg/100 cm2 for API. • The task based exposures for the sampling duration were compared against the eight-hour OEL-TWA. The surface concentrations of contaminant were compared against the recommended SGV. 7
  8. 8. Monitored Unit Operations Monitored Unit Operations: • QC Sampling • Dispensing and Pre-blending • Excipient charging and blending • Tablet Compression 8 Personal Exposure Monitoring and Static Air Sampling: • Task based samples collected for the operator(s) involved in the unit operations • Static samples located according to International Society for Pharmaceutical Engineering (ISPE) Good Practice Guide: Assessing the Particulate Containment Performance of Pharmaceutical Equipment • Air samples in corridor and wipe samples
  9. 9. Changes Between Surrogate and API Monitoring • QC Sampling Work Practices - The operator performed cleaning after API sampling. Weight of materials handled - 20 g, 40 g and 60 g for surrogate and 5 g*2 for API Sampling duration - 18 min for surrogate and 64 min for API • Dispensing and Pre-blending Work practices - One small bag of API was sampled and transferred through the pass box of isolator Weight of materials handled - 55.5 kg for surrogate, 28.9 kg (1st iteration) and 55.7 kg (2nd and 3rd iteration) for API Sampling duration - 59 min and 123 min for surrogate and 79 to 348 min for API) 9
  10. 10. Changes Between Surrogate and API Monitoring • Excipient charging and blending Work practices Sampling duration – 7 min and 8 min for surrogate, 61 min to 78 min for API • Tablet Compression Work practices - The operator opened the tablet IBC after compression during API monitoring. Equipment - Loose connection between collecting chute and polybag during API monitoring. Weight of materials – Consistent with Dispensing and Pre-blending 10 Surrogate API-1st and 2nd iteration API-3rd iteration
  11. 11. Results 11 • QC Sampling with Glove Box Surrogate (µg/m3) API (µg/m3) Personal < 0.0279 10.8 Between the glove ports < 0.0274 < 4.35 Potential contributory factors for variability in Surrogate and API results: • The operator opened and covered the API drum outside the glove box. • The operator opened the glove box and performed cleaning after QC sampling of API.
  12. 12. Results 12 • Dispensing and Pre-blending Surrogate (µg/m3) API (µg/m3) Primary Operator 0.0686 < 0.0171 < 3.75 < 1.25 < 1.42 Assistant Operator 5.86* 1.99 < 3.78 < 0.863 1.31** SBV 5.13 2.99 < 3.1 < 0.871 < 1.24 Bag-out port 0.0182 0.0429 < 3.18 NA < 1.31 Pass box 0.0499 < 0.00714 < 3.15 < 0.838 4.07** Outlet of filtered air 0.0248 0.0245 < 3.14 < 0.851 < 1.32 Drum loading port 0.036 0.0682 < 3.14 < 0.857 < 1.33 Control board 0.223 0.268 < 3.12 < 0.841 < 1.28 Potential contributory factors for variability in Surrogate and API results: * The package of the surrogate might be contaminated which potentially contributed to the high surrogate level for assistant operator. ** One small bag of API was sampled inside the isolator and transferred out of the isolator from the pass box. The assistant operator opened the pass box for 6 to 7 times to transfer materials.
  13. 13. Results 13 • Charging Excipient into IBC Which Contained Surrogate or API Surrogate (µg/m3) API (µg/m3) Primary Operator 3.83 0.199 6.25 6.3 < 4.68 Near the SBV < 0.0717 0.208 21.6 10.4 < 4.63 Potential contributory factors for variability in Surrogate and API results: • Change of work practices.
  14. 14. Results 14 • Compression Surrogate (µg/m3) API (µg/m3) Operator 1 0.57 0.173 2.91 0.922 3.54 Operator 2 0.121 0.0632 < 0.731 < 0.743 1.77 Collecting chute 0.0698 0.00286 < 0.747 3.75 1.24 Control board 0.00637 < 0.00171 < 0.724 < 0.754 < 0.76 SBV of tablets IBC 0.0175 0.022 < 0.762 < 0.747 < 0.739 SBV of material IBC 0.0102 < 0.00176 < 0.739 < 0.753 < 0.744 SBV of material IBC 0.00925 < 0.00171 0.83 < 0.77 < 0.751 Potential contributory factors for variability in Surrogate and API results: • Loose connection between collecting chute and polybag. • Work practices: the operator opened tablet IBC to check the status of the tablets.
  15. 15. Results 15 • Corridor Air Samples and Wipe Samples for API (Partial) Wipe samples Range (µg/100 cm2) On the handle inside compression room 30.15 On the handle inside coating room 0.9 On the handle inside IPC room 7.04 On the recording table inside IPC room 2.47 and 9.4 Wipe samples outside the process rooms (23 samples) < 0.6 to 1.19 (22 samples) and 16.9 (1 sample-on the handle compression room) Air samples Range (µg/m3) Corridor (22 samples) < 2.47 (below the Reporting Limit) The operator took tablet samples with hands (disposable Nitrile gloves worn). Touching of contact surfaces (e.g., door handle) with contaminated gloves contributed to the high results of the swabs.
  16. 16. Recommendations to reduce exposures • Evaluate feasibility of providing in-situ cleaning of the glove box used for QC sampling. • Raise employee awareness on health hazards of API and the importance of following safe work practices through initial and refresher training programs. • Include the particulate containment devices, such as isolator and split- butterfly valves into the preventive maintenance program and ensure the devices function properly. • Evaluate feasibility of collecting rejected tablets and tablets for QC in a contained system. If plastic bags have to be used, ensure all connections are tight to reduce particulates emissions. 16
  17. 17. Recommendations to reduce spread of API Contamination • Define Red Zone (potentially contaminated area such as API handling areas), Yellow Zone (less contaminated where PPE is removed) and Green Zone (not contaminated such as corridors). • Use shoe covers and disposable coveralls. Remove potentially contaminated gloves, shoe covers and coveralls, place them into double plastic bags and discard them into a waste container located in Yellow Zone. • Separate air locked entry and exit for operators and separate airlock door/window/corridor for taking equipment in and out. • Wipe clean potentially contaminated equipment and materials such as cart before taking it out of the API handling area. • Develop and implement procedures to use two pair of gloves. Replace outer pair, when contaminated. 17
  18. 18. Lesson Learnt • Surrogate monitoring is indicative and not confirmative of the API particulate containment and exposures. • Variability in personal exposure results for surrogate and API was significant. Relying of surrogate monitoring results to determine API exposure is questionable. • API exposure monitoring is needed to confirm particulate containment and employee exposures. • Variability in static air monitoring results for surrogate and API was not significant and hence surrogate monitoring results are indicative of containment efficiency for API • As expected, work practices contribute to the high personal exposures and surrogate – API result variability 18
  19. 19. Thanks you. Any questions? Shaobo Chen, Senior Industrial Hygienist Bob.chen@issehs.com 19

Presentation ai hce 2017 bob chen updated-3.0

Vues

Nombre de vues

211

Sur Slideshare

0

À partir des intégrations

0

Nombre d'intégrations

116

Actions

Téléchargements

5

Partages

0

Commentaires

0

Mentions J'aime

0

×