Standard Operating Procedure for Sampling of Raw Materials in Pharmaceuticals
Standard Operating Procedure for Sampling of Raw Materials in Pharmaceuticals
1. Purpose:
To provide a standard operating procedure for Sampling of Raw Materials in Pharmaceuticals.
2. Scope:
The scope of this SOP is applicable Sampling of Raw Materials in Pharmaceuticals at [company name].
3. Responsibility:
3.1 Quality Control Laboratory Personnel: Sampling of Raw Materials, Cleaning of sampling devices and equipment
3.2 Quality Control Laboratory Supervisor: Supervision of the activities.
3.3 Head Quality Control Laboratory: Ensure the compliance of the SOP.
4. Definitions:
Not applicable
5. Procedure:
• On receipt of Raw Material in the warehouse, the warehouse enters details of received material in the material management software. As soon as the Goods Inward Note (GRN) is prepared, the Laboratory Information Management System (LIMS) database for Raw Material awaiting sampling is updated.
• Daily, Quality Control laboratory personnel responsible for the raw material section (Raw Material section head) will check the list of material populated in the system displays as material to be tested.
• Raw material section head will also inquire about the priority of the manufacturing department before planning Raw Material Testing or Refer Monthly Production Planning Schedule.
• Raw material section head will allocate the material to be sampled to the Quality Control Laboratory Person responsible for sampling Raw Material (Sampler) in the LIMS.
• The sampler will log in to the LIMS and print the Raw Material sampling worksheet.
• The sampler0, will reach the warehouse department and request warehouse staff to take the material to be sampled inside the sampling area through the Material Movement airlock.
• The sampler shall enter the sampling area through a man airlock with appropriate gowning.
• The sampler shall verify the cleanliness of the sampling area before bringing the material inside the sampling area and starting the sampling activity.
• On arrival of Raw Material inside the sampling area, sampler will verify the material label, manufacturers’ batch number, control number/ A.R. No./ unique identification number of material (generated by material management software of the organization), and ensure that material arrived in the room is the same material that is supposed to be sampled as per sampling worksheet.
• The sampler will also ensure that the Raw Material is free from external damages. If the container is found damaged, it shall be marked separately and informed to the warehouse person, Raw material section head, and Quality Assurance Person.
• The sampler will verify the Raw Material container using a sampling worksheet to ensure the following:
• Raw Materials shall have the label as “Quarantine” to each container with details of Material Name, Material Code, Control No./ A.R. No., Material Manufacturer’s name/ Vendor name, Manufacturer Batch No., Manufacturing Date, Expiry Date, Quantity of material received, Number of containers received, Pack Size, and Warehouse document serial number.
• Materials shall not be accepted when the material name is not listed in the approved vendor list, if foreign particles are observed during sampling, Certificate of Analysis (CoA) not received with the material, or any other abnormal observation.
• The raw material section head shall verify the CoA received from the material manufacturer and compare it against the specification implemented in the organization. The raw material section head will ensure that the analysis results of the material manufacturer are within the organization’s specification limit. In case of any deviation noted, it shall be informed to the Quality Control laboratory head and Quality Assurance head to take a call on whether material shall be accepted or rejected.
• Before starting the sampling, ensure that the Sampling Room’s environmental condition, such as Temperature, Relative Humidity, and Differential Air Pressure, is within the defined and acceptable range.
• Only one material shall be sampled at a time in Sampling Area.
• Ensure that Reverse Laminar Airflow (RLAF) is switched “ON” at least before [specify the time which is established through recovery study, it vary from 10 minutes to half an hour]. Record the pressure differential across the pre-filter, intermediate, and HEPA filter and ensure that readings are within the defined range. In case of any abnormality, sampling shall not be started. Instead, inform to the engineering department to rectify before beginning the sampling activity.
• Containers to be sampled shall be taken within the safe zone of RLAF. A sampling of volatile materials shall be done at solvent sampling and dispensing area.
• Before starting the sampling of material, the sampler shall follow safety precautions. Sampler needs to use required Personal Protective Equipment (PPE) during sampling. Example, Nose Mask, Hand Gloves, Safety Goggles, etc.
• Material Safety Data Sheet [MSDS] should be handy in the area.
• Sampler needs to ensure the availability of cleaned and dry sampling tools prior to sampling activity. In addition, it shall be ensured that the validity of the clean sampling tool is within the defined period as per the clean sampling tool hold time to study.
• For Active Pharmaceutical ingredients, material dedicated sampling tools shall be used to prevent any potential for cross-contamination. [Shared sampling tools can be used when a scientific sound cleaning validation program is in place for sampling tools].
• Materials for which the identification library is created in the material identification modules such as FT-NIR, Raman Spectroscopy, the identification test of the raw material container shall be done using validated and calibrated instruments for each container. Enter the details of analysis in FT-NIR/ Raman Spectrophotometer logbook.
• Results of identification shall be recorded in the Raw Material Sampling worksheet, and system-generated results’ print shall be attached along with the worksheet.
• Before starting the sampling activity, make an entry in the RLAF logbook for sampling activity, such as material name, control number, RLAF start time, and sampling start time.
• Once the sampling activity is completed, enter the sampling end time.
• Samples quantity for the sample to be collected shall be as per sampling worksheet. Sample quantity shall be the sum of sample for analysis (Chemical and Microbiology Sampling), and Control/ Reference sample.
• Identification using FT-NIR/ Raman Spectrophotometer shall be made separately for each container.
• A sampling of material shall be done from each container. Quantity of sample to be collected from each container shall be calculated by dividing the total required quantity by the number of containers to be sampled.
• Sample for Microbiology Testing shall be collected in the sterile sampling bag, and remaining samples [for chemical analysis as well as control/ reference sample] shall be collected in a separate sampling bag.
• Sample from each container to be collected in sampling bag, and the composite sample shall be prepared.
• For the particle size distribution analysis, the sample shall be collected in a separate container and kept in closed condition, and opened immediately before analysis. The process will help prevent any moisture absorption in the sample, which could impact the results.
• While sampling the each container, affix the label on each container indicating that the container has been sampled. Also, affix the “under test” label on each container over the quarantine label. The total under test label to be generated will be the sum of a number of containers sampled, plush one for raw material report.
• Under test label shall have following details on it:
Material Name
Material Code
Control No. / A.R. No.
Manufacturer Name
Manufacturer Batch No.
Manufacturing Date
Expiry Date
Quantity
Number of packs
Pack size
Sampled By
Date
• In the case, the Sampling Worksheet needs to be reprinted; it can be done with prior authorization and justification.
• Ensure that sampling tools such as Stainless Steel Scoop, Spatula, Measuring Cylinder, Pipette, etc., are cleaned before use.
• After completion of sampling activity, the sampling area will be cleaned as per respective SOP for Cleaning of Sampling Room.
• Record the cleaning activity in the logbook, which consists of cleaning start time, cleaning end time, the person who did cleaning activity and checked by.
• Material with the category of OEB (Occupational Exposure Band) 3 or higher shall be sampled in the isolator/ sampling chamber with glove port.
• The sampler shall perform sampling activity under RLAF; however, it shall be ensured that only material to be sampled remain inside the safe zone of RLAF and the sampler remain outside the safe zone.
• The sampler shall wear hand gloves while sampling activity. If the sampler touches the corrugated box or any outer part of the container that can contaminate the raw material, the sampler should immediately change the hand glove.
• The sampler should not lean on the open container to avoid the potential for contamination.
• The sampler should ensure that there should not be any spillage of material inside the area to minimize the potential for the area and environmental contamination.
• The sampler shall repack the material container adequately after sampling to ensure adequate raw material storage after sampling.
• Moisture-sensitive materials shall be stored in a polyethylene bag lined with an aluminum bag with an airtight seal.
• In case of the specific requirement described in the Raw Material specification/ Method of analysis, for sampling, sample packing or any other instruction for sample maintenance, it shall be followed to ensure the adequate sample is available for analysis.
• Sampling procedure for solid material:
• The sample shall be collected from the container to get the representative sample. Sample shall be collected from Top, Middle, and Bottom of the material container.
• To achieve this, a sampling rod can be used. In case of container size is smaller, a spatula can be used to collect the sample from a different height of the container.
• A sampling of material shall be done from each container. The quantity of sample to be collected from each container shall be calculated by dividing the total required quantity by a number of containers to be sampled.
• In case of 100% container identification is to be done in the quality control laboratory, a sample for identification shall be collected in a separate container.
• Once the sampling is done, mix the sample and divide it for composite analysis and control sample/ reference sample as per Sampling Plan.
• Invert and rotate the sample container/ polybag for approximately 10-15 times to homogenize the sample.
• Label the composite and control sample appropriately for identification. The control sample shall be stored in a simulated smaller container similar to its original pack.
• In case of material is received in 14 or fewer containers, sub-composite sample preparation is not required. However, if the material is received in more than 14 containers, the sub-composite sample shall be prepared using the formula 0.4√N as per p-plan (N is number of containers received).
• Example of sub-composite sample preparation:
• If 200 containers are received for one material, sub-composite sample preparation will be 0.4√200 = 6 sub-composite samples. 1st sub composite sample shall be prepared from 1 to 33, second from 33 to 66, and so on. Each sub-composite sample shall be homogeneously blended in the selected sub-container.
• Prepare the final composite sample by mixing approximately equal quantities from each sub-composite sample and homogenizing it.
• Record the preparation of sub-composite and final composite sample preparation in the sampling worksheet.
• Sample for Microbiology testing shall be collected in a sterile polybag. Sample for particle size distribution analysis shall be collected separately. Depyrogenated sampling tool shall be sued for sample for Bacterial endotoxin test (BET) and it shall be collected in sterile polybag.
• Sampling procedure for liquid and semi-solid raw material:
• Sampling for liquid material shall be done under RLAF. The liquid solvent shall be sampled under a fuming hood.
• The liquid sample shall be stirred with a sampling tool prior to sampling.
• The sample shall be withdrawn from the container’s top, middle, and bottom.
• The sample shall be collected in the sampling bottle, and then it shall be closed adequately.
• Semi-solid or viscous material shall be sampled with the help of stainless steel spatula suitable to collect the sample.
• For identification purpose, sample shall be collected in separate container. The composite sample shall be collected in a single bigger bottle and divided into two parts, sufficient for sample for analysis and control/ reference sample.
• Sample for Microbiology testing shall be collected in a sterile container. Depyrogenated sampling tool shall be used for the Bacterial endotoxin test (BET) sample, and it shall be collected in a sterile polybag.
• Sample storage of light-sensitive materials:
• Light sensitive materials sampling shall be done under sodium vapor lamp/ monochromatic light to prevent photo degradation of material as well as sample.
• Amber color glass bottle/ suitable bottle shall be used for liquid samples. The solid material sample shall be collected in a polyethylene bag and then stored in a black polyethylene bag or aluminum bag.
• A sampling of protein and peptide material:
• In case of material is too sensitive to handle multiple times, sampling of material can be done along with the material dispensing activity. In case potency value is required to be used during material dispensing to adjust the quantity of material for production, results of potency can be used from material manufacture’s CoA.
• Sampling of cold chain material:
• Before sampling cold chain material, the material shall be thawed to bring the temperature to controlled room temperature. The process and requirement of thawing shall be done as per material specification and method of analysis of respective raw materials.
• Once the sampling is completed, the sample for analysis and control/ reference samples shall be labeled for their respective purpose.
• The material container shall be affixed with an “Under test” label on each container.
• Transfer the material to its respective location in the warehouse with the help of a warehouse person.
• Send the sampling tools for the cleaning. In case of tool cleaning to be done in a different area, wrap the tools in the polybag to prevent the spillage of residue to prevent the contamination of other areas. Affix the label on the to be cleaned tool as “To be cleaned”.
• Clean the sampling tool as per the validated cleaning procedure.
• Once the cleaning of the sampling tool is done, affix the appropriate label as “Cleaned tool” with the validity of cleaning.
• The sampler shall hand over the sample to the raw material section head. Raw material section head shall receive the sample by making an entry in sample inward register and placing the sample in respective storage cabinet as per required storage condition.
• In the case of cold chain material, the material is to be placed in respective storage conditions within the stipulated time suggested for the respective material.
• Control sample/ reference sample shall be stored in the respective storage location for control sample as per defined storage condition of the material.
• If the FT-NIR or Raman identification system is out of order, 100 % sample identification shall be done in the quality control laboratory using the FTIR instrument. The sample shall be collected for 100% identification from each container in addition to the composite sample.
• Sampling procedure for Gaseous sample:
• When compressed gas needs to be sampled, ensure that the cylinder is correctly placed at its location so that is does not dislocate.
• Ensure that the required minimum pressure is available in the gas cylinder. Operate the valve carefully to prevent any damage to the valve as well as ensure the entire gas would not escape from the cylinder
• Ensure that sampling of the gaseous sample is done in an open environment to prevent any potential health hazard.
• Ensure that the cylinders are supplied as per standard color coding standards for respective gas. If color-coding is not as standard, the cylinder shall not be sampled, and it shall be rejected by making an entry in the material sampling worksheet.
• Attach the regulator to the cylinder and then attach the sample container, such as the ready-to-use balloon, to a regulator. Purge the sample container/ balloon before sampling.
• Open the regulator valve carefully and collect the gas in the sample container/ balloon.
• Close the regulator valve and remove the sample container/ balloon.
6. Frequency
Sampling of raw material for all incoming raw materials
Sampling of material under re-test
7. Formats
7.1 Format for Raw Material sampling worksheet
| Parameters | Observation |
| Material Information verification | |
| Material Name | |
| Material Code | |
| Control No./ A.R No. | |
| Material Manufacturer | |
| Manufacturer’s Batch No. | |
| Manufacture ring Date | |
| Expiry Date | |
| Quantity received | |
| Number of containers received | |
| Pack Size | |
| Pack Profile | |
| Physical Verification | |
| Material appearance | |
| Contamination/ foreign matter | |
| Physical condition of container/ Any signs of damage | |
| Intactness of container seal | |
| Sampling Room environmental condition | |
| Manufacturer’s certificate of analysis availability | |
| Manufacturer’s certificate of analysis parameters compliance against company’s specification | |
| Total quantity sampled | |
| Sample collected from number of containers | |
| Identification FT-NIR/ Raman Spectrophotometer complies for all containers |
7.2 Format for list of Raw Material and sample quantity
| Sr. No | Raw Material Name | Material Code | Quantity for Identification test (per container) | Sample quantity for analysis and Control/ reference Sample | Total sample quantity | Sample quantity for Microbiology analysis |
7.3 Format for Logbook of Raw Material sampling (Content of logbook is as follows)
Date
RLAF/ Fuming Hood Start time
RLAF/ Fuming Hood Equipment Id.
Verification of Sampling Area Cleanliness
RLAF Magnahelic Gauge Pressure reading of Primary, Intermediate and HEPA filter
Material Name
Sampling Start Time
Manufacturer Batch No.
Control Number/ A.R. No.
Material Quantity Received
Quantity Sampled
Sampling Stop Time
Material Sampled By
RLAF/ Fuming Hood and weighing balance Cleaning Start Time and End time
Cleaned By
Checked By
7.4 Logbook for Cleaning Record of Sampling Tools (Content is as follows)
Sr. No.
Date
Material Name
Control No./ A.R. No.
Sampling Device Id. No.
Validity of cleaning
Cleaned By
Checked By
7.5 Logbook for Raw Material Control/ Reference Sample Management
Sr. No.
Date of Sampling
Material Name
Batch No.
Control No./ A.R. No.
Quantity of Control/ Reference Sample
Material manufacturer name
Quantity Withdrawal
Purpose of Withdrawal
Sample withdrawn by
Sign/ Date
Retention period of sample
Due date of sample destruction
Destroyed by (Sign/ Date)
Checked by
7.6 Control sample specimen label
Material Name
Sampled on (date)
Control No.
Retained up to (date)
Sampled by (Sign/ Date)
7.7 Specimen Label for under test label
Material Name
Material Code
Control No. / A.R. No.
Manufacturer Name
Manufacturer Batch No.
Manufacturing Date
Expiry Date
Quantity
Number of packs
Pack size
Sampled By
Date
7.8 Specimen Label for Sample for analysis
Material Name
Material Code
Control No. / A.R. No.
Quantity
Chemical analysis/ Microbiology Analysis/ Particle size distribution analysis/ BET Analysis
Sampled By
Date