SOP on Cleaning Program
Objective : To lay down a procedure for cleaning program.
Scope : This procedure is applicable in all departments of formulation plant.
Responsibility :
Officer/ Executive-Concerned department shall be responsible for implementation of this SOP.
Head-QA shall be responsible for compliance of this SOP.
Abbreviations and Definitions
Critical Equipments : Equipments that comes directly in contact of product.
Area : Include Floors, walls, ceilings.
Contaminants : Anything which is not included in the product processing.
SLS : Sodium lauryl sulphate
Procedure :
Aspects of cleaning
All the equipments/vessels and area used during manufacturing shall be cleaned and sanitized at appropriate intervals e.g. at the time of product changeover or after five batches of one product manufactured in campaign basis, as per their respective SOPs.
Cleaning procedure developed / designed for equipment/vessel and area cleaning shall be validated as per Validation Master Plan.
QA shall prepare the protocol for cleaning validation studies and perform the validation studies in co-ordination with other departments.
Cleaning validation studies shall be designed considering ‘worst case’ criteria (chemical limits and microbial limits).
QA shall evaluate the need of validation of cleaning procedures time to time.
Validated cleaning procedure shall include removal of product from area and equipments with approved cleansing agent (0.5%w/w of SLS), removal of residual approved cleansing agent(0.5%w/w of SLS), and confirmation of removal of approved cleansing agent by validated analytical procedure.
Validated cleaning procedure shall be revalidated if there is significant change in product formulation, change or major modification of processing equipment, change in cleaning agent, modification or change in cleaning equipment or cleaning procedure.
Cleaning program shall start with dispensing of raw material as compounding a finished product requires equipment with large product contact surface.
All the scoops, spatulas, funnels, sampling aids, tanks, filter housings, areas, equipments / vessels used during manufacturing including FBD bags etc. shall be validated for cleaning as they are considered as the equipments which may cause contamination.
Effectiveness of sanitization of the process equipment, storage tanks, area (floor, walls) shall be evaluated through validated methodologies.
Cleaning procedure
Cleaning of new equipment:
Equipment shall be passivated (if stainless steel material) as per the passivation protocols/ procedures, (if already not passivated by the vendor).
Removal of residual passivating agent shall be ensured by applying suitable analytical methodologies.
Clean the equipment with water (Potable water and then finally rinse with purified water; before using purified water, drain it minimum for two minutes) and assess the cleaning visually to the level of satisfaction.
Dry the equipment using lint-free dry and clean cloth and/or use compressed air to dry the same.
There are two types of cleaning procedure for equipments used in manufacturing i.e. cleaning procedure type A and type B.
Cleaning Procedure type A shall be followed for product change over and/or after every five consecutive batches of the same product. It includes following steps:
Cleaning of area and equipments with cleansing agent i.e.0.5% w/w SLS in case of product containing Nimesulide and products prepared in Soft gel area using brush or other cleaning aids as per procedure mentioned in their respective SOPs for cleaning of equipment.
A wash water sample can be collected if specified in the respective SOP for cleaning, as per SOP by IPQA and can be verified visually or can be sent to Quality Control along with sample request, for determination of residual drug and cleansing agent.
Cleaning procedure type B shall be performed between batch to batch changes over of same product. It includes following steps:
Vacuum cleaning of the area shall be done.
Equipment shall be mopped with clean moist lint free cloth (moist with purified water) and later with clean dry cloth.
Cleaning of Area
Clean the manufacturing or store areas as per SOP.
Cleaning is valid till product changeover or for five consecutive batches whichever is earlier.
If the area is not to be used immediately after cleaning, then lock the area after displaying the status labels.
Need of re-cleaning after certain time interval of cleaning of area shall be assessed by IPQA, if required re-cleaning shall be undertaken before using that area for carrying manufacturing activities.
Cleaning of equipment
Clean the equipments (as per relevant SOPs for cleaning of equipments) using nylon brush and cleaning agent solution and then removing the cleaning agent solution with potable water and later rinse with purified water.
Use clean dry lint free cloth or compressed air to dry the equipment.
Cleaning checklist for the particular equipment (wherever applicable) shall be filled by the operator performing the cleaning of equipment at the time of cleaning.
Checklist and adequacy of the steps shall be verified by the production supervisor, while IPQA personnel shall verify the cleaning of the equipment visually and then only shall finally approve the checklist.
Similarly “CLEANED” status labels shall be filled by production personnel and shall be verified by IPQA personnel only after inspecting the equipment visually for cleanliness.
If the equipment is not to be used immediately then cover the equipment using clingfilm, so that equipment remains free of contaminants and shall bear the status label.
Before using the equipment, remove the clingfilm, visually examine the equipment if found satisfactory use it otherwise cleaning of the same shall be planned.
For following cases B-type cleaning shall be done:
For same quality of excipients, (Examples Flavors, Colours etc.)
When going from the drug product of lower strength to the drug product of higher strength.
5% w/w solution of SLS shall be used for the equipments of Soft Gel Production area and products containing Nimesulide.
Hold Time for uncleaned equipments/ vessel shall be not more than 72 hours and for cleaned equipments the Hold time shall be 14 days from the date of cleaning of that equipment and after that time period Type “A” cleaning shall be performed.