GOWNING PHILOSOPHIES : HIGH POTENT OSD FACILITIES

Suitable gowning in pharmaceutical facilities act as a shield protecting both product and person. Operator being a source of contamination should be covered suitably and also should be protected properly for exposure against potent and toxic products. Generally, gowning approach is directly or indirectly related to the product and process requirements. More Personnel Protective Equipment (PPE) are required as a part of gowning, while operating in a High Potent Oral Solid Dosage (HPOSD) facility. Whereas, sterilized wear is a requirement for aseptic manufacturing areas.

Gowning is performed in  separate rooms or airlocks adjacent to operation area, where  personnel put on protective clothing after leaving the first area and before entering the second area. These airlocks can be more than one depending on procedural and HVAC requirements. The de-gowning operation should not violate the cross contamination control condition achieved in common areas. Procedures also should address employee movement during the course of the day to toilet facilities, and areas such as the cafeteria and offices. Mirrors, signage for instructions on gowning procedures, storage of gowns, trash for gowns, and benches are typical components of a gowning/de-gowning area. Gowning room should have same area classification to which person is entering.

*  High Potent  may include OEL 3,  depending on STTWA calculations.

Gowning procedures differ for different cultures around the world. In Asia, unlike west, street shoe removal happens in a separate room prior to primary gowning. In Europe, gowning starts from top. Some procedures insist on having cross over bench and some simply follow the demarcation for clean and unclean. Some facilities have attached cubicle for complete dress change and some perform that in open locker hall.

Gowning Qualification should be established initially and periodically for the capability of an individual to don the complete gown. For sterile gown in an aseptic manner in aseptic manufacturing. And PPE in protective manner for hazardous(potent or toxic) areas.

Gown Integrity Tests :

1.      Gelbo Lint Test: Determines the relative number of lint particles released from a fabric

2.      Martindale Abrasion Test (ASTM D4966): A visual test of the abrasion resistance of fabric using a standard abrasive surface and specified force to assess fabric integrity and lint production.

3.      Fluid & Bacteriophage Barrier (ASTM F1671): Measures resistance of materials used in protective clothing to blood borne pathogens using viral penetration 2psi and ambient pressure.

Gowning Philosophies for OSD Facilities:

Over gowning for classified areas

For OSD Facilities there are typically three levels of product exposure: general, protected, and controlled. Generally, the division of levels is directly related to the product or product component exposure, as well as to the physical environment and function within the facility. The highest level of risk for product exposure is a controlled space, compared to a general space which has the least stringent protective parameters due to virtually zero product exposure.

Example of a “general” space would be a shipping  and loading area for manufacturing, which is adjacent to a GMP warehouse. The product, material, or components are typically protected by an additional packaging layer surrounding the primary packaging or container with little to no risk of product exposure to the environment. An area, such as secondary packaging, could be considered a “protected” space because, while the product is not exposed, the primary package’s handling and physical environment can have an effect on the finished product. Finally, a “controlled” space would include weigh and dispensing rooms where product is directly exposed to the environment. The amount of contact with a product has a direct correlation to gowning procedures within an OSD manufacturing and packaging facility.

Areas with higher risk assessments will require more and varied levels of gown changes. As one moves from common areas to process operation areas the level of product protection and personnel protection will increase. The more interaction that the personnel have with the product will increase the Level of Protection. Minimizing the level of interaction that personnel will have with the product, through closed or semi-closed operations will decrease the level of gowning required.

In Multi-product High Potent Oral Solid Dosage (HPOSD) facility, unit operations are performed inside the dedicated suites for different products (running simultaneously). Operator gowns, if used as common for all the suites, are potential source of contamination. GMP suggest additional over gowning for each suite to avoid contamination. It reduces the chances of contamination between the two running suites with different product attached with the common clean corridor.

Gowning philosophy to be applied for Multi-product High Potent Pharmaceutical Facilities considers the high risks involved with product contamination and operator safety. Handling hazardous product in a form of powder is the crucial aspect of any HPOSD Facility. Highly potent material can cause critical health hazard due to exposure, if not handled properly with proper gowning and personnel protection equipment.

For every hazardous product substance, occupational exposure limit(OEL) is identified for its upper limit on the acceptable concentration  in particular room. Short Term Time Weighted Average (STTWA) studies are performed considering Occupational Hazard Limit (OHC), dust potential and exposure time in order to decide the exposure potency level for containment design.

There are three levels of protection for product and operator. First level of protection is at the equipment level, where product gets isolated from the environment. Depending on process design, product transfer philosophy is defined. It can be closed transfer or open. Equipment like isolators with split valves can be used. Exposure cannot be 100% prevented by equipment alone but it’s the primary layer of protection where potential risks can be minimized substantially. Second level of protection is at the room environment, where particle count is controlled with the help of HVAC system. The production suite is kept under negative pressure in comparison to the connected airlocks and adjoining corridor. Depending on risk assessment, Bag-in-Bag-out (BIBO) type air filters can be used at terminals and at the plenum and sometimes at the exhaust. Third level of protection is at the Operator level, where person is isolated with the help of Personnel Protective Equipment (PPE). Connecting airlock rooms are provided for gowning and de-gowning to avoid contamination. Entry airlock is considered cleaner than the exit airlock.

Gown and PPE worn in a manufacturing suite can become contaminated with highly potent materials. Facilities should be provided and established procedures should be used which allow operators an appropriate safe means to remove contaminated PPE. During de-gowning, operators should be prevented from breathing in contaminants and contaminants dislodged from the PPE should be prevented from spreading over a wide area. Mist showers may be used to hold dusty contaminants to the full body coveralls. The water volume should be minimized to avoid exposing operators through a non-waterproof coverall. Minimizing water spray also reduces the opportunity for overspray and the amount of liquid waste from showering. Where PPE components, such as Respiratory Protective Equipment(RPE), are to be reused, facilities for cleaning and maintenance should be part of the de-gowning area. After de-gowning, gowns and PPE are collected in double polybags  with in the de-gowning room and are taken for decontamination and washing. 

Various level of gowning for high potent OSD manufacturing:

Ideally, operator should enter in a multiproduct facility after taking a factory dress change in the controlled environment. Donning Clean factory dress after striping street cloths is recommended practice for Non-Classified GMP areas like warehouse and secondary packing halls. Donning of Secondary dress over the clean factory dress in secondary gowning rooms is required for classified areas common for different manufacturing suites. And for entering various potent manufacturing suites, secondary dress is removed and tertiary dress with PPE are donned in tertiary gowning rooms (fig.1).

Figure 1: Gowning Sequence for Multi-Product Facility

Option of wearing Grade D dress after removing street dress(directly) is also there to reduce weight of cloths. In this particular option, separate street dress/primary change rooms for classified areas are required to be designed from different direct entry point (fig.2). This saves time and avoids complications of changing dress three times.

Figure 2: Gowning Sequence for Multi-Product Facility (with slim suit)

For single product manufacturing facility, it is again less complicated, where PPE and potent suit donning can be done in secondary change entry room (fig.3) .

Figure 3: Gowning Sequence for Single-Product Facility 

Figure 4

High potent Manufacturing Suite gowning procedure:

Some fraction of product leakage is assumed from the equipment/isolator. Some particles are supposed to shed over the gown while working inside the suite. Below are some practices being followed by different manufacturing groups to attend this issue.

In some of the concepts, person exits through entry airlock after de-gowning inside the exit airlock, this allows person to take back secondary gown which he was wearing before entering (fig.4). Whereas in one of the preferred option, two way dynamic pass box is provided between entry and exit airlock, this allows the passage for garment & PPE from one airlock to another, this maintains proper segregation between the two airlocks (fig.5).

1.      Air shower

2.      Mist Shower

3.      Vacuum System

Figure 5

While exiting manufacturing suite, operator enters the air shower cubical to remove particles from his gown. In such case, air shower should have supply & return air systems and it should also be evaluated for BIBO filter grade requirement. Some manufacturing groups prefer vacuum systems over air showers.  Air showers are turbulent and pressurized system and they do not ensures removal of particles. On the other side, it is difficult to devise a vacuum cabin, which can suck potent particles effectively. So, a piped apparatus with a brush nozzle can be used which can run over the dress  over the dress. Air shower can be replaced with Mist shower with a drain trap if the dust potential and chances of containment breech are more.

In some of the concepts, person exits through entry airlock after de-gowning inside the exit airlock, this allows person to take back secondary gown which he was wearing before entering (fig.4). 

Figure 6

Whereas in one of the preferred option, two way dynamic pass box is provided between entry and exit airlock, this allows the passage for garment & PPE from one airlock to another, this maintains proper segregation between the two airlocks (fig.5).

Some fraction of product leakage is assumed from the equipment/isolator. Some particles are supposed to shed over the gown while working inside the suite. Below are some practices being followed by different manufacturing groups to attend this issue. 

Emergency provisions:

Usage of mist/water shower during emergency (breach of containment) is common philosophy being used. It is better to provide it inside the exit airlock to contain the spillage. Breathing air system is another system which can be provided in the suite, which can be hooked to the breathing apparatus or with the PAPR (Powered Air Purifier Respirators) during any emergency.

Bibliography:

Baseline Guide Volume 2: Oral Solid Dosage Forms,

Baseline Guide: Volume 1 - Active Pharmaceutical Ingredients;

Guidance for Industry : Sterile Drug Products Produced by Aseptic Processing —

Current Good Manufacturing Practice