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Airborne Contaminants in the Pharmaceutical Blow-Fill-Seal Environment
KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering, Building Services Engineering.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Stockholm: KTH , 2010. , 151 p.
Identifiers
URN: urn:nbn:se:kth:diva-27388OAI: oai:DiVA.org:kth-27388DiVA: diva2:376924
Public defence
2010-12-15, V1, Teknikringen 76, KTH, Stockholm, 14:00 (English)
Opponent
Supervisors
Note
QC 20101213Available from: 2010-12-13 Created: 2010-12-13 Last updated: 2010-12-13Bibliographically approved
List of papers
1. Some observations on airborne particles in blow-fill-seal filling rooms
Open this publication in new window or tab >>Some observations on airborne particles in blow-fill-seal filling rooms
2007 (English)In: PDA journal of pharmaceutical science and technology, ISSN 1079-7440, Vol. 61, no 3, 147-153 p.Article in journal (Refereed) Published
Abstract [en]

Pharmaceutical products produced by blow-fill-seal (BFS) technology are manufactured in clean rooms of different cleanliness classes. Regulatory authorities set requirements on factors such as the maximum allowed airborne particle concentration in filling rooms with BFS machines. To meet the requirements of the authorities, the supply air is HEPA-filtered. The necessary flow of HEPA-filtered air depends on the particle generations from the BFS machines (source strength). One method of reducing the airborne particle concentration in the filling rooms is to install local exhaust systems in order to remove generated particles. Knowledge of particle dispersion and source strength are necessary to enable correctly dimensioned airflows. In this paper, the dispersion pattern of particles was studied at one filling machine. The partial source strength was determined for four different filling machines. The source strength is the total number of airborne particles per second generated by the BFS machine and the process. The value of the partial source strength will be dependent on the efficiency of the local exhaust system. Partial source strength is defined as the estimated theoretical quantity of particles per second emitted from the filling machine into the filling room. The results show that the partial source strength varies widely between the different filling machines. The source strength levels vary between 102 and 10 7 particles (≥ 0.5 μm) per second. Furthermore, the results show that the efficiency of the local exhausts can be improved by design adjustments.

Keyword
Airborne particles, Aseptic filling, Blow-fill-seal
National Category
Civil Engineering
Identifiers
urn:nbn:se:kth:diva-25729 (URN)17722481 (PubMedID)2-s2.0-34547736423 (Scopus ID)
Note
QC 20101029Available from: 2010-10-29 Created: 2010-10-29 Last updated: 2010-12-13Bibliographically approved
2. Some observations on airborne particles in the critical areas of a blow-fill-seal machine
Open this publication in new window or tab >>Some observations on airborne particles in the critical areas of a blow-fill-seal machine
2009 (English)In: PDA journal of pharmaceutical science and technology, ISSN 1079-7440, Vol. 63, no 1, 71-80 p.Article in journal (Refereed) Published
Abstract [en]

Regulatory authorities set requirements on factors such as maximum allowed airborne particle concentrations in critical areas and the surrounded environment. An important issue when producing sterile drugs by aseptic processing with blow-fill-seal technology is to achieve Class 100 (ISO Class 5) in the critical area. To meet these requirements high efficiency particulate air (HEPA)-filtered airflow is used to dilute and remove airborne particles. The required airflow is dependent on the quantity of generated particles. The purpose of this paper is to present the measures taken to reduce airborne particle concentrations at critical areas of a blow-fill-seal machine. The methods being used in the experimental studies are smoke visualization and particle measurements. The results show that particle concentrations can be reduced by minor changes of process variables. By changing the process variables, particle concentrations - number of particles (≥0.5 μm) per cubic foot - in the shroud (filling zone), extrusion zone, and the filling room were approximately reduced as follows: ∼90% in the shroud (filling zone), ∼90% in the extrusion zone, and ∼40-60% in the filling room. It should be noted that the presented results are limited to one type of blow-fill-seal machine and this paper is a continuation of an earlier published paper by the authors in the PDA journal.

Keyword
Airborne particles, Aseptic filling, Blow-fill-seal
National Category
Civil Engineering
Identifiers
urn:nbn:se:kth:diva-25735 (URN)19455943 (PubMedID)2-s2.0-66349134725 (Scopus ID)
Note
QC 20101029Available from: 2010-10-29 Created: 2010-10-29 Last updated: 2010-12-13Bibliographically approved
3. The use of computational fluid dynamics for the study of particle dispersion routes in the filling area of a blow-fill-seal process
Open this publication in new window or tab >>The use of computational fluid dynamics for the study of particle dispersion routes in the filling area of a blow-fill-seal process
2010 (English)In: European Journal of Parenteral and Pharmaceutical Sciences, ISSN 0964-4679, Vol. 15, no 1, 5-11 p.Article in journal (Refereed) Published
Abstract [en]

An important issue when producing sterile drugs or medicinal products by aseptic processing with blow-fill-seal technology is to achieve an airborne particle cleanliness of ISO Class 5 for particles ≥0.5 micron for US and EU, and ISO Class 4.8 for particles ≥5.0 micron for EU compliance in the critical area, which includes the filling zone. Most blow-fill-seal machines are equipped with a filling shroud in the filling area, above the ampoules. The shrouds are often pressurised using either HEPA-filtered air or sterile filtered air. The pressure inside the shroud results in a downwards directed airflow, which creates a cleaner environment around the open ampoules during the filling process than the immediate surroundings in the bowels of the machine. The clean environment within the shroud also provides protection for the fillingmandrel and nozzles. This paper describes the use of computational fluid dynamics to simulate air velocity magnitudes andmass flow rates as ameans of better understanding particle dispersion routes in the filling area of a blow-fill-seal process and the impact different parameter settings can have on airborne particle concentrations in the filling area. The results show that the movements of the mandrel, together with its nozzles, is the main cause of particles present in the filling shroud during the manufacturing process. The computational fluid dynamics results suggest that particle concentrations can be reduced by changing the mandrel velocity and the mandrel shape. It should be noted that results presented in this paper are limited to one type of BFSmachine.

Keyword
Airborne particles, Blow-fill-seal, CFD, Computational fluid dynamics, Shroud
Identifiers
urn:nbn:se:kth:diva-27389 (URN)2-s2.0-77953339275 (Scopus ID)
Note
QC 20101213Available from: 2010-12-13 Created: 2010-12-13 Last updated: 2010-12-13Bibliographically approved
4. Particle conentrations in small volume parenterals produced by aspectic blow-fill-seal technology
Open this publication in new window or tab >>Particle conentrations in small volume parenterals produced by aspectic blow-fill-seal technology
2010 (English)In: European Journal of Parenteral and Pharmaceutical Sciences, ISSN 0964-4679, Vol. 15, no 3, 87-92 p.Article in journal (Refereed) Published
Keyword
airbone particles, blow-fill-seal, aseptic, small volume parenteral
Identifiers
urn:nbn:se:kth:diva-27390 (URN)
Note
QC 20101213Available from: 2010-12-13 Created: 2010-12-13 Last updated: 2010-12-13Bibliographically approved

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