PDA于2003年首次发布了“Points to Consider for Aseptic Processing“，并于2015年和2016年分别发布了Points to Consider for Aseptic Processing parts 1和2。2023年10月，PDA更新了“Points to Consider No.1 Aseptic Processing”，本次修订取代了2015和2016文件中讨论的话题。
4.30 The speed of air supplied by unidirectional airflow systems should be clearly justified in the qualification protocol including the location for air speed measurement. Air speed should be designed, measured and maintained to ensure that appropriate unidirectional air movement provides protection of the product and open components at the working position (e.g. where high-risk operations occur and where product and/or components are exposed). Unidirectional airflow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value) at the working position, unless otherwise scientifically justified in the CCS. Airflow visualization studies should correlate with the air speed measurement.
5.3 For the manufacture of sterile medicinal products 4 grades of clean room can be distinguished.
Grade A: The local zone for high risk operations, e.g. filling zone, stopper bowls, open ampoules and vials, making aseptic connections. Normally, such conditions are provided by a localised air flow protection, such as laminar air flow work stations or isolators. Unidirectional air flow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value), the point at which the air speed measurement is taken should be clearly justified in the protocol. During initial qualification and requalification air speeds may be measured either close to the terminal air filter face or at the working height, Where ever the measurement is taken it is important to note that the key objective is to ensure that air visualization studies should correlate with the airspeed measurement to demonstrate air movement that supports protection of the product and open components with unidirectional air at the working height, where high risk operations and product and components are exposed. The maintenance of unidirectional airflow should be demonstrated and validated across the whole of the grade A area. Entry into the grade A area by operators should be minimized by facility, process and procedural design.
PDA对2017版的反馈意见如下：
Comment: Section 5.3 states prescriptive guidance for air speed as well as an expectation for justification of sampling distance. Air velocity guidance may or may not be appropriate for unidirectional flow in all cases and at all points within the Grade A zone. ISO 14644-3 clearly indicates that the test for unidirectional air flow and referencing 0.4 – 0.6 m/s should be taken within 150-300 mm of the filter face. While using the ISO guidance for qualification or re-qualification may be suitable, implication that the guidance velocity values have any validity elsewhere in the Grade A zone is not accurate. The prescription of a standard velocity is not necessary, and should depend on line and process configuration. The requirement for individual determination of standard measuring distance is not necessary, if a standard distance is already available.
Proposed change: Remove recommended velocity, but add guidance recommendation for measurement distance. "Unidirectional air flow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value), the point at which the air speed measurement is taken should be clearly justified in the protocol. During initial qualification and requalification air speeds may be measured either close to the terminal air filter face or at the working height, Airflow systems that are designed to be unidirectional should provide a homogeneous air velocity as measured within 150 – 300mm of the filter face that is adequate to prevent the ingress of particulate from the less-clean surrounding environment into the working area.
4.32 The speed of air supplied by unidirectional airflow systems should be clearly justified in the qualification protocol including the location for air speed measurement. Air speed should be designed, measured and maintained to ensure that appropriate unidirectional air movement provides protection of the product and open components at the working height (e.g. where high risk operations and product and/or components are exposed). Unidirectional airflow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value) at the working position, unless otherwise scientifically justified in the CCS. Airflow visualization studies should correlate with the air speed measurement.
PDA对2020版的反馈意见如下：
Comments: As currently written, the section may be mis-interpreted as requiring the prescribed guidance value. In addition, as currently written, the section may be misinterpreted as requiring air velocity measurement for non-Grade A zones. In addition, some of the language referring to air speed requires clarification.
Suggested text: The speed acceptable range for velocity of air supplied by Grade A unidirectional airflow systems should be clearly justified in the qualification protocol including the location for air speed measurement. Airflow speed velocity should be designed, measured and maintained to ensure that appropriate unidirectional air movement provides protection of the product and open components at the working height (e.g. where high risk operations and product and/or components are exposed). Unidirectional airflow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value) at the working position, unless otherwise scientifically justified in the CCS. Airflow visualization studies should correlate with the air speed measurement. Grade A Unidirectional airflow velocity should be correlated to airflow visualization studies.
Justification: "Speed" has been replaced with "velocity" or velocity related terms, because it refers to a vector quality including both speed and direction. "Grade A" has been inserted in the section, because unidirectional flow may pertain to other than Grade A areas; therefore, it should be clear that these requirements are meant for Grade A and not necessarily for any and all unidirectional airflow system. The section stating the guidance range has been removed, because it may be considered by some to be a prescribed range and limit. Airflow velocity should be designed, measured and maintained to ensure that, where it is specified, appropriate unidirectional air movement provides protection of the product and open components at the working height. However, the most suitable velocity range is highly dependent on several factors other than airflow velocity. These include:
o the individual production equipment calling for Grade A protection
o the individual Unidirectional Air Flow Device, UDAF, supplying air
o the geometries of the room in which the equipment and UDAF is situated
Prescribing air flow velocity ranges changes focus from the importance of understanding and evaluating the effectiveness of the flow in terms of protecting the product and critical surfaces. Note that the target interval is a historic one that does not align with current ISO guidance. The proof of concept for the airflow velocity is in the air flow visualization. The correlation between velocity measurements and visualization is key when velocity is used to verify continued compliance with the visualized airflow.
