August 13, 2021: Pharmaceutical Interview Questions and Answers
#SterileManufacturingAreaGrade #GradeVsISO #SterileAreaGowning
1. What are the sterile manufacturing area grades? What are the operations to be carried out in each area?
For the manufacture of sterile medicinal products 4 grades 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 laminar air flow work station. Laminar air flow systems should provide a homogeneous air speed in a range of 0.36–0.54 m/s (guidance value) at the working position in open clean room applications. The maintenance of laminarity should be demonstrated and validated. A uni-directional air flow and lower velocities may be used in closed isolators and glove boxes.
Grade B: For aseptic preparation and filling, this is the background environment for the grade A zone.
Grade C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products.
2. Explain correlation between Area Grades, Area Class and ISO Classification “At Rest” and “In Operation”.
| Grade | ISO Class number (At rest) | Class (At rest) | ISO Class number (At rest) | Class (At rest) |
| A | 4.8 | 100 | 4.8 | 100 |
| B | 5 | 100 | 7 | 10,000 |
| C | 7 | 10,000 | 8 | 100,000 |
| D | 8 | 100,000 | Not defined | Not defined |
Note:
For Grade A the airborne particle classification is ISO 4.8 dictated by the limit for particles ≥ 5.0 μm.
For Grade B (at rest) the airborne particle classification is ISO 5 for both considered particle sizes.
For Grade C (at rest and in operation) the airborne particle classification is ISO 7 and ISO 8 respectively.
For Grade D (at rest) the airborne particle classification is ISO 8. (In operation no classification is defined).
Reference – Rules and Guidance for Pharmaceutical Manufacturers and Distributors (MHRA)
3. Provide example of operations to be carried out in the various grades for sterile manufacturing facility.
Examples of operations to be carried out in the various grades are as follows:
| Grade | Examples of operations for terminally sterilised products. |
| A | Filling of products, when unusually at risk. |
| C | Preparation of solutions, when unusually at risk. Filling of products. |
| D | Preparation of solutions and components for subsequent filling. |
| Grade | Examples of operations for aseptic preparations. |
| A | Aseptic preparation and filling. |
| C | Preparation of solutions to be filtered. |
| D | Handling of components after washing. |
Reference – Rules and Guidance for Pharmaceutical Manufacturers and Distributors (MHRA)
4. Explain clothing requirements for each grade of manufacturing are for sterile manufacturing facility.
Grade A/B: Headgear should totally enclose hair and, where relevant, beard and moustache; it should be tucked into the neck of the suit; a face mask should be worn to prevent the shedding of droplets. Appropriate sterilised, non-powdered rubber or plastic gloves and sterilised or disinfected footwear should be worn. Trouser-legs should be tucked inside the footwear and garment sleeves into the gloves. The protective clothing should shed virtually no fibres or particulate matter and retain particles shed by the body.
Outdoor clothing should not be brought into changing rooms leading to grade B and C rooms. For every worker in a grade A/B area, clean sterile (sterilised or adequately sanitised) protective garments should be provided at each work session. Gloves should be regularly disinfected during operations. Masks and gloves should be changed at least for every working session.
Grade C. Hair and where relevant beard and moustache should be covered. A single or two-piece trouser suit, gathered at the wrists and with high neck and appropriate shoes or overshoes should be worn. They should shed virtually no fibres or particulate matter.
Grade D. Hair and, where relevant, beard should be covered. A general protective suit and appropriate shoes or overshoes should be worn. Appropriate measures should be taken to avoid any contamination coming from outside the clean area.
Reference – Rules and Guidance for Pharmaceutical Manufacturers and Distributors (MHRA)
