SOP For cleaning validation of injection filling machine is described in this post which you can follow in the section of the Quality Assurance Department.

INTRODUCTION:

The Validation of Machine/ Equipment Cleaning Procedures is to prevent cross-contamination or Adulteration of drug products. The Cleaning Validation is not only ensuring the compliance of the regulatory requirements, but a  more important benefit for performing cleaning procedure validation is the identification and the correction of the potential problems which could compromise the safety, efficacy or quality of the subsequent batches of drug product. Several serious problems can be prevented by performing Cleaning Validation, all these problems are related to the adulteration, therapeutic safety and efficacy or overall quality of the product over its shelf life.

OBJECTIVE

The main objective of Cleaning Validation is to prove that the product contact parts of machine/equipment or production area has been cleaned and that the contamination level has been reduced below to an acceptable level. To achieve these acceptable levels, cleaning procedures need to be established and validated, sampling and analysis will be carried out for this purpose to assure that the machine/equipment or area of interest complies with specified limits. Cleaning Validation will also verify the effectiveness of cleaning procedure.

SCOPE

This document on cleaning validation is intended to address special consideration and issues pertaining to validation of cleaning procedures for machine/equipment or area used in manufacturing of Pharmaceutical. This document is also intended to establish inspection consistency and uniformity with respect to equipment cleaning procedures. This document is intended to cover validation of equipment cleaning for the removal of   contaminants associated to the previous product, residues of cleaning agents as well as the control   of potential microbial contaminants.

RESPONSIBILITY

Production Officer 

Q.A Officer

Microbiologist

Q.C Analyst

ACCOUNTABILITY

Manager Production

Manager Quality Assurance

Manager Quality Control

VALIDATION PROGRAM

A validation program generally comprises of three consecutive successful replicates to establish that the procedure is reproducibly effective. If the equipment of the similar size, design and construction is cleaned by the same procedure, studies need not to be conducted on each unit as long as a total of three successful replicates are done on similar piece of equipment; this concept is known as equipment grouping.

Acceptance Criteria

Sr #

Testing Parameter

Acceptance Criteria

1

Physical determination

The visual examination of the equipment verifying that no visible residues or particulate matter present on the equipment

2.

Chemical Determination

NMT 0.1 % of the normal therapeutic dose of any product to appear in the maximum daily dose of the subsequent product. OR NMT 10 ppm of any product to appear in the next product.

3.

Microbiological Determination

Active/Passive Air Sampling

F-DAB Test

Swab Test (Area/Equipment)
















PROCEDURE

There are following sampling procedures that are considered to be acceptable.

Direct Surface Sampling (Swab Method): 

Area difficult to clean and which are reasonably clean can be evaluated by direct surface sampling method (Swab Method), leading to establish a level of contamination or residue per given area. The residue that are dried out or are insoluble can be sampled by Swab Method.

Physical Testing:

Along with taking any type of the samples, it is important to use visual inspection as well to ensure the process acceptability.

Chemical Testing:

The specificity and sensitivity of the analytical methods should be determined. If levels of contamination or residue are not detected, it does not mean that there is no residual contaminant present after cleaning. It only means that the level of contaminant is lower than the sensitivity or detection limit of the analytical method.

Test the samples i.e. Swab Sample, Rinse Sample for detection of active or inactive impurity according to relevant testing procedure of the ingredient to be detected and provide quantitative results.    

Microbiological Testing:

Passive Air Sampling:

Disinfect the media filled plates externally with an approved disinfectant.

Transfer the plates to the desired location in a clean sealed container.

Expose the media filled plates by taking off the lid aseptically and place it besides the open plate facing downwards. Do not reach over the exposed plate.

Allow the plate to remain open for one hour.

After completion of exposure time, place the lid on the plate taking care such that the plate does not get contaminated.

Label the plate with site, date and area.

Transfer the plates into the plate box and return to Q.C. Micro Lab. for incubation.

After receiving the plates from production, incubate them in the incubator at 37°C for 48 – 72 hours.

After incubation count the number of CFU on each plate and report the record.

Incubate one media filled plate along with the exposed plates to serve as negative media control.

F-DAB Test:

Disinfect the plates with an approved disinfectant and allow to dry for 10 – 15 minutes.

Transfer the plates in a sealed container from Q.C. Micro Lab. to the production area.

Divide the plate into two halves on the backside of media filled plate using a Marker, label it as right and left.

Ask the operator to press his finger tips on to the agar surface. Close the plate.

Label with the name of the operator, date and area.

Transfer the plates to Q.C. Micro Lab. for incubation.

Incubate the plates at 37°C for 48 hours in an incubator

After incubation count the colonies on the colony counter and report as No. of CFU per hand.

Swab Test

The Sterilized Cotton Swabs prepared on S.S sticks.

Material is transferred into sterile area for swab test after disinfection.

Remove the sterilized swab, soak in phosphate buffer and touch to the surface to be checked.

25cmarea is touched against each soaked swab.

Place back the swab into the tube containing phosphate buffer and label.

Transfer the tested swab to micro lab for microbiological test.

Pour plate method is used to check the contaminants.

Plates are incubated for 48 hours, the result are declared as number of CFU per part or surface.

Inspection Criteria:

After receiving intimation for cleaning of machine/equipment or area, witness the cleaning according to    

the predetermined cleaning procedure.

During cleaning, check and note down the following points.

Description of machine/equipment/area:____________________________

Major Product contact components:________________________________

Product Contact Area:___________________________________________

Previous product:_______________________________________________

Batch No.:_____________________________________________________

Previous Batch completed on:______________________________________

Equipment cleaned on:____________________________________________

After cleaning the Equipment used on:________________________________

Subsequent Product:______________________________________________

Name of API:____________________________________________________

Batch Size of the subsequent product: ________________________________

Maximum daily dose of the subsequent Product:_________________________

Detergent / Solvent used:___________________________________________

Composition of the detergent used:____________________________________

Cleaning Tools:____________________________________________________

Ancillary Utilities:__________________________________________________

Cleaning Cycles:___________________________________________________

Cleaned by:_______________________________________________________ 

Supervised by:_____________________________________________________

After cleaning, take sample either by direct surface sample (Swab Method) or rinse sample depending upon the nature of machine/equipment and product.

Send the sample to QCD along with technical information sheet for analysis.

QCD analyzes the sample according to written procedure and gives the results to validation department.

Validation team analyzes the results, if the results comply with the specified limit, then the    

machine/equipment is considered as cleaned and is allowed for further process.

If the results do not comply with the specified limit, then test until it is cleaned. This concept involves

Cleaning, sampling & testing until an acceptable residue limit is obtained. Also record the following.

Sampling Method followed:___________________________________________

Cleaning Procedure:_________________________________________________

Follow the procedure for cleaning of vial filling machine.

Facilities/Responsible Personnel/Equipment/Material & Documentation

Facilities:

 

 

 

 

Identification of Responsible Personnel:

 


Name

Job Title

Signature

 

Microbiologist

 

 

Q.C. Analyst

 

 

QA inspector

 

 

Production Officer