The cleaning and disinfection of GMP production area’s is a tricky subject when you’re setting up your GMP Quality Management System. Each company has it’s own level of detail. We’ve seen SOP’s with thirty pages and SOPs with five pages.
There is no right or wrong. If your SOP is unidirectional, well-written and follows Good Writing Practices, it may very well be thirty pages. If you have to go back-and-forth between five pages all the time and the SOP is too ambigious, it may be much more difficult too review than the thirty page SOP.
This post attempts to introduce some principles which will help you in reviewing/creating your own SOP for cleaning of GMP controlled area’s.
The starting point for the establishment of a cleaning SOP for production area’s is the establishment of requirements to avoid contamination of products and related manufacturing processes. The exclusion / reduction of any kind of contaminants are thus the prime objective.
Contaminants may originate from:
- materials used in the manufacturing process,
- surfaces of contact,
- products themselves (drug substances, intermediates or raw materials),
- the manufacturing environment,
- utilities (water, steam, nitrogen, compressed air, heating/cooling systems, etc.),
- persons intervening in the process.
Contaminations are differentiated as follows:
- cross contamination (of a product/material with another product/material)
- non-microbial particulate contamination (non-viable particles)
- biological/microbiological contamination (viable particles/micro-organisms)
To achieve the appropriate cleanliness levels in the relevant manufacturing processes the following factors are to be scrutinized:
- air cleanliness,
- personnel hygiene and clothing,
- personnel interference (working practice),
- material design (material of construction, surface finishes, room finishes, equipment, open system/enclosed system, utensils, etc.),
- material cleanliness,
- material flow,
- waste flow,
- cleaning and disinfection procedures etc.
Required sections in a gmp cleaning and disinfection sop
Different regulatory requirements may have different requirements. But if we take a look at the “worldwide standards”, meaning;
- The European Union EudraLex Volume 4
- The WHO TRS’s
- The U.S. FDA CFR’s
Then you should have (at least) the following sections in your GMP cleaning and disinfection SOP of Production Area’s;
- Roles & Responsibilities
- Definitions and Abbreviations
- Required Resources
- Removing leftover dirt (if applicable)
- Cleaning the area
- Disinfecting the X (clean steam/water/etc.) system (if applicable)
- Disinfecting the area
- Finalization / rounding-up
- Attachments (if any)
- Revision History
Level of Detail
The level of detail should be commensurate with the criticality of the area. Cleaning non-classified hallways won’t be that detailed. Cleaning your aseptic production area will be a lot more detailed.
When you’re writing the SOP always take your audience into account. Your cleaning staff may not be up-to-date with the latest abbreviations/developments in the pharmaceutical industry.
We will illustrate the level of detail using two examples; 1 SOP for the cleaning of the raw materials dispensing area and 1 SOP for the cleaning of the microbiology laboratory.
Level of detail – raw material dispensing area
These are some sections from a raw material dispensing area cleaning SOP. These are for illustrative purposes only; showing the level of detail at a particular company. This level of detail may not be applicable to your situation.
- Sweeper : To clean the area.
- Workman : To follow the SOP.
MATERIALS AND EQUIPMENT :
- Liquid soap
- Vacuum cleaner
- First mop the weighing balance and platform with a dry cloth.
- Clean the floor of the dispensing room with the liquid soap solution .
- Ensure that the walls are cleaned properly with a wet cloth. Followed by a dry cloth.
- Clean the area once a dispensing activity for a product is over. Clean the dispensing table with the help of vacuum cleaner or clean duster. Clean the area with a wet cloth.
- Mopping is to be done for all the area if dispensing of different product is performed.
LEVEL OF DETAIL – microbiology lab
These are some sections from a microbiology laboratory cleaning SOP. These are for illustrative purposes only; showing the level of detail at a particular company. This level of detail may not be applicable to your situation.
- Microbiologist: To follow this procedure
- Assistant Manager Q.C.: Ensure this procedure is followed.
MATERIALS AND EQUIPMENT :
- Approved disinfectant solution.
- 70 % Isopropyl Alcohol.
- Clean lint free duster.
- Nylon broom.
- Water for Injection (Bulk)
- Dust bin
- *some materials have been omitted from this list
- S.S.- Stainless steel
- P.P.- Poly propylene
- IPA – Isopropyl Alcohol
- Prepare disinfectant solutions as per SOP PCS-SOP-001A.
- Remove all used material such as; dilution tubes, pipette tips, disposable pipettes, glassware, contaminated agar plates, cotton swabs, syringes etc. from the laboratory working benches and from the laminar air flow benches. Separate the material with culture and without culture and keep them in the trolley for washing.
- Keep the media tubes, plates and dilution sets with culture to be discarded in S.S. buckets. Pour the disinfectant solution in tubes, plates in container and cover it with aluminum foil or PP caps for an hour.
- Clean the floor with a dry nylon broom. Start this activity from the farthest point in lab/room incubators and proceed towards the entrance of lab/room incubators i.e. from inside out. Collect accumulated debris, put into the covered dustbin.
- Then clean the laminar bench/working table with a clean dry lint free cloth.
- Spray 70 % IPA over the laminar bench and allow the contact time of 5.0 minutes to complete. Then mop all parts of both laminar benches with disinfectant solution. Spray 70% IPA on working table and clean it after contact time with lint free duster.
The level of detail for a cleaning SOP depends on a number of factors. Where the most important factor is the criticality of the activity that occurs in the area. Subsequently you will have to consider the audience, the opinions of Subject Matter Experts and what cleaning materials can/may be used on the surfaces for example.