SOP for Sampling of Raw Material in Pharmaceutical Industry

Sampling of raw materials is an important part of pharmaceutical quality control. Proper sampling helps ensure that the material tested by the Quality Control (QC) laboratory is representative of the received batch and suitable for the required analysis.
Good Manufacturing Practice (GMP) principles emphasize scientifically sound sampling procedures, prevention of contamination and cross-contamination, proper identification of sampled containers, and complete documentation.
This article provides a general Standard Operating Procedure (SOP) for sampling of raw materials. The actual procedure used at a pharmaceutical manufacturing site should always be approved by the organization's Quality Assurance (QA) and Quality Control departments and aligned with applicable regulatory requirements.

1.0 Purpose

To establish a standardized procedure for sampling raw materials so that samples are collected, handled, identified, documented, and transferred to the Quality Control (Q.C.) laboratory in a consistent and controlled manner.

Proper sampling is important because laboratory results are meaningful only when the collected sample is representative of the material being evaluated. FDA guidance states that sampling procedures should specify the number of containers, sampling location, and quantity of material to be collected, based on an appropriate sampling plan.

2.0 Scope

This SOP applies to the sampling of raw materials at:

(Name and Address of the Company)

It covers the sampling of Active Pharmaceutical Ingredients (APIs), excipients, solvents, and other applicable raw materials received by the facility.

The procedure should be applied together with the approved material specifications, sampling plan, testing procedures, cleaning procedures, and applicable GMP requirements.

3.0 Responsibilities

3.1 Q.C. Executive/Designee

The Q.C. Executive/Designee shall:

Understand and follow this SOP.
Perform sampling according to the approved sampling plan.
Use appropriate sampling equipment and containers.
Prevent contamination and cross-contamination.
Record sampling activities accurately.
Transfer collected samples to the QC laboratory under appropriate conditions.

3.2 Q.C. Head/Designee

The Q.C. Head/Designee shall:

Review this SOP and its implementation.
Ensure that authorized personnel perform sampling.
Ensure that sampling plans are appropriate for the material and intended testing.
Review sampling records and deviations where applicable.

3.3 QA Manager/Designee

The QA Manager/Designee shall:

Review and approve the SOP.
Ensure that the procedure is consistent with the site's quality system.
Ensure that applicable GMP and documentation requirements are addressed.

4.0 Materials and Equipment

Depending on the material and sampling activity, the following may be required:

Clean and dry sampling devices
Stainless-steel liquid sampler
Solid sampling device
Clean poly bags
Amber glass bottles with screw caps
Transparent stoppered containers
Light-protective containers
Airtight containers
Sterile containers for microbiological samples
Clean sampling spoon
Appropriate labels
70% IPA or another approved disinfectant
Required personal protective equipment (PPE)

The equipment selected should be suitable for the material being sampled and should not introduce contamination or alter the sample.

5.0 Sampling of Raw Materials

5.1 Precautions

5.1.1 Clean Sampling Materials

Always use clean and dry sampling containers and sampling devices appropriate for the material.

5.1.2 Cleaning and Sanitization

Clean the sampling device according to the approved cleaning procedure before use.

For samples intended for microbiological testing, use appropriately sanitized equipment and containers and follow the site's approved microbiological sampling procedure.

5.1.3 One Consignment at a Time

Only one consignment of material should be sampled at a time to minimize the possibility of mix-ups and cross-contamination.

5.1.4 Sampling Devices

Use suitable and dedicated or appropriately cleaned sampling devices for different materials.

Sampling equipment should be compatible with the material and should not adversely affect the sample.

5.1.5 Personal Protective Equipment

Wear the PPE specified by the facility, such as:

Mask
Gloves
Cap
Appropriate protective clothing
Appropriate footwear

5.1.6 Sampling Booth Cleaning Status

Before starting sampling, verify that the sampling booth has an appropriate and valid cleaning-status label.

Do not begin sampling if the required cleaning status cannot be confirmed.

5.1.7 Use of Sampling Booth

The designated sampling booth should be used for sampling Active and Excipient Raw Materials according to the site's approved environmental and facility requirements.

5.1.8 Hygroscopic and Light-Sensitive Materials

Sampling of hygroscopic or light-sensitive raw materials should be performed under the environmental conditions specified in the approved procedure.

Where a dedicated sodium-lamp arrangement and dehumidification facility are provided, use them according to the approved equipment and sampling procedures.

5.1.9 Light-Sensitive Materials

Where required by the approved procedure, switch on the sodium lamp before sampling light-sensitive material for the specified period.

5.1.10 Sampling Booth Differential Pressure

Before sampling, verify and record the differential pressure/manometer reading of the sampling booth or LAF unit.

Where the approved site procedure specifies a range of 7–15 mm of water, ensure that the reading is within that specified range before sampling.

Do not assume that this range is universally applicable to every sampling booth; the equipment's qualified operating range and approved SOP should be followed.

5.1.11 Sequence of Sampling

All applicable solid and liquid materials should be sampled in the designated sampling area according to the approved sampling procedure.

Where microbiological testing is required, collect the microbiological sample using the approved aseptic or hygienic sampling procedure before other sampling activities, where specified by the site's procedure.

5.1.12 Material Receiving Documentation

Receive the Material Receiving Intimation, duly signed by the Store In-Charge, together with the applicable physical verification report.

Enter the relevant information into the Raw Material Sampling Register maintained by the QC Department.

Typical information includes:

Name of material
Date of receipt
Supplier name
Batch/Lot number
Manufacturing date
Expiry date or retest date
A.R. number
Quantity received
Number of containers
Other applicable information

5.1.13 Assignment of Sampling

The Q.C. Head/Designee shall assign sampling activities to an authorized and trained Q.C. Officer/Executive.

5.1.14 Approved Vendor Verification

Before sampling, verify that the material has been supplied by an approved vendor according to the company's current Approved Vendor/Supplier List.

If the supplier is not approved, sampling should not proceed unless the applicable quality procedure specifically permits otherwise.

5.2 Sampling Containers

5.2.1 Selection of Container

Select the sample container according to the nature, characteristics, and testing requirements of the material.

The selection should follow the current approved sampling-container list.

5.2.2 Solid Materials

For solid materials, use clean and suitable poly bags or other approved sampling containers.

5.2.3 Liquid Materials

Use clean and dry amber glass bottles with suitable screw caps for liquids when protection from light is required.

For solvents, use an appropriate clean container compatible with the solvent and approved by the site procedure.

5.2.4 Light-Sensitive Samples

Collect light-sensitive materials in suitable light-protective containers, such as approved black polyethylene bags or other validated/properly specified containers.

5.2.5 Moisture-Sensitive Materials

Collect moisture-sensitive materials in suitable clean, dry, airtight containers.

5.2.6 Microbiological Samples

Use sterile sampling containers for samples intended for microbiological examination.

The sampling process should be designed to prevent contamination of the sample and maintain sample integrity.

5.3 Sampling Preparation

5.3.1 Verification of Material Details

Before sampling, compare the information on the Material Receiving Intimation with:

Supplier label
Material label
Batch/Lot number
Container number
Quantity
Manufacturing date
Expiry/retest date
Other relevant information

5.3.2 External Inspection

Before transferring containers to the sampling area, check that:

Containers are externally clean.
Containers are properly closed.
Labels are legible.
Seals are intact where applicable.
There is no leakage.
There is no visible damage.
The physical condition is satisfactory.

5.3.3 Approved Supplier Check

Confirm that the material has been received from an approved supplier.

If the supplier is not approved, do not proceed with routine sampling until the discrepancy has been evaluated according to the applicable quality procedure.

5.3.4 Environmental Conditions

Record the applicable sampling booth environmental parameters, such as:

Differential pressure
Temperature
Relative humidity

The specified limits should be based on the qualified operating range and approved site procedure.

5.3.5 Handling of Discrepancies

Immediately report discrepancies such as:

Damaged containers
Broken seals
Incorrect labels
Missing information
Leakage
Unapproved supplier
Evidence of contamination
Any other abnormal condition

The issue should be communicated to the Store In-Charge and appropriate QC/QA personnel and handled through the applicable deviation or non-conformance procedure.

5.4 Selection of Containers for Sampling

5.4.1 Active Raw Materials

For Active Raw Materials, collect samples from all containers where individual container identification testing is required by the approved specification, regulatory requirement, or sampling plan.

FDA guidance states that representative samples and scientifically sound sampling plans should be used for raw materials and APIs.

5.4.2 Excipient Raw Materials

For Excipient Raw Materials, select containers according to the approved sampling plan.

Where the site-approved procedure uses a √N + 1 approach, apply it as specified by that approved procedure.

The √N + 1 approach should not be presented as a universal regulatory requirement because the appropriate sampling plan depends on factors such as material variability, supplier history, criticality, and quantity required for testing.

5.4.3 Container Numbering

Identify selected containers clearly.

For example, if 30 containers are received, the containers may be identified as:

1/30
2/30
3/30
4/30

and so on.

5.4.4 Sampling from Different Levels

Where appropriate and practical, collect samples from different levels of the material, such as:

Top
Middle
Bottom

The quantity collected should be based on the approved sampling plan and the testing requirements.

WHO sampling guidance emphasizes representative and, where appropriate, random sampling across a consignment and consideration of container condition and material uniformity.

5.5 Sampling Procedure

5.5.1 Bring the selected container into the designated sampling area according to the approved material-handling procedure.

5.5.2 Verify the material identity and container number before opening the container.

5.5.3 Open the container carefully to avoid contamination, spillage, or damage to the packaging.

5.5.4 Collect the required quantity of sample using the appropriate sampling device.

5.5.5 Avoid unnecessary exposure of the material to environmental conditions.

5.5.6 Transfer the sample into the appropriate labeled sample container.

5.5.7 Close the sample container immediately after collection.

5.5.8 Close and reseal the original material container properly after sampling.

5.5.9 Mark sampled containers appropriately to indicate that a sample has been withdrawn.

FDA guidance specifically recommends that containers from which samples are taken be carefully reopened, reclosed, and marked to indicate that sampling has occurred.

5.5.10 Sample Quantity

The sample quantity should be sufficient for:

Required analysis
Repeat testing, where justified and permitted
Retention sample requirements
Other approved testing requirements

The quantity should be defined in the approved sampling plan or relevant specification.

5.5.11 Sample Transfer

Transfer the collected samples to the QC laboratory under appropriate supervision and storage/handling conditions.

Ensure that sample identity and traceability are maintained throughout the process.

5.6 Preparation of Composite Samples

5.6.1 Excipient Raw Materials

Where composite sampling is permitted by the approved sampling plan, collect an equal or specified quantity from each selected container.

Transfer the portions into a clean, suitable polyethylene bag or approved container.

Mix the material thoroughly using a clean and suitable sampling spoon or approved mixing method.

Where required, prepare separate samples for:

Testing
Retention

The preparation of composite samples should follow the approved sampling plan and should not compromise the ability to identify individual-container problems where individual testing is required.

5.6.2 Active Raw Materials

For Active Raw Materials, collect the required quantity from each applicable container according to the approved sampling plan.

Where individual identification testing is required, maintain the individual samples separately and identify them with the corresponding container number.

Where a composite sample is permitted for assay or other testing, combine appropriate equal quantities from the applicable individual samples.

Mix the combined sample thoroughly using an appropriate clean sampling/mixing device.

Prepare the required testing and retention samples according to the approved sampling plan.

5.7 Labeling of Samples

Each sample container should be appropriately labeled.

The label should include, as applicable:

Name of material
Batch/Lot number
A.R. number
Supplier name
Sample number
Container number
Date of sampling
Sample type
Quantity
Storage condition
Sampler's initials/signature

Proper identification and documentation are essential elements of GMP and quality control.

5.8 Cleaning of Sampling Equipment

After completion of sampling:

Clean the sampling device according to the approved cleaning procedure.
Inspect the device for cleanliness.
Allow it to dry where applicable.
Affix or update the appropriate cleaning-status label.
Store the device in its designated location.

Cleaning should be adequate to prevent contamination and cross-contamination between materials.

5.9 Sampling Records

Record completion of sampling in the Raw Material Sampling Register.

The record should include, as applicable:

Name of material
Batch/Lot number
A.R. number
Supplier name
Date of receipt
Date of sampling
Number of containers received
Number of containers sampled
Sample quantity
Sample type
Container numbers sampled
Name/signature of sampler
Reviewer details, where applicable
Observations
Deviations, if any

All entries should be clear, accurate, legible, contemporaneous, and traceable.

Regulatory GMP guidance emphasizes documented sampling procedures and records as part of pharmaceutical quality control.

6.0 General Precautions

6.1 Prevent cross-contamination throughout the sampling operation.

6.2 Use only clean and suitable sampling devices.

6.3 Use appropriate sampling containers based on material characteristics.

6.4 Do not sample damaged, leaking, unidentified, or improperly labeled containers until the discrepancy has been evaluated.

6.5 Maintain complete traceability between the original material container and the collected sample.

6.6 Do not return excess sample material to the original container unless specifically permitted by an approved procedure.

6.7 Keep the material exposed for the shortest practical time during sampling.

6.8 Follow appropriate environmental requirements for hygroscopic, moisture-sensitive, temperature-sensitive, or light-sensitive materials.

6.9 Clean the sampling area after completion of sampling.

6.10 Dispose of waste and disposable sampling materials according to the applicable waste-management procedure.

7.0 Why Proper Raw Material Sampling Is Important

Raw material sampling is not simply a laboratory activity. It is an important part of the pharmaceutical quality system.

A poor sampling procedure can produce a laboratory sample that does not accurately represent the batch. This can result in incorrect conclusions about the quality of the raw material.

WHO describes GMP as a quality-assurance system intended to ensure that medicinal products are consistently produced and controlled according to appropriate quality standards. GMP also aims to reduce risks such as contamination, cross-contamination, mix-ups, and incorrect labeling.

For this reason, sampling should be:

Scientifically justified
Representative
Controlled
Properly documented
Performed by trained personnel
Performed using suitable equipment
Designed to prevent contamination and cross-contamination

8.0 References

8.1 WHO – Good Manufacturing Practices

The World Health Organization provides GMP principles covering pharmaceutical production, quality control, documentation, personnel, premises, materials, and related quality systems.

Official reference:
WHO – Good Manufacturing Practices

8.2 WHO – Guidelines for Sampling of Pharmaceutical Products and Related Materials

WHO provides guidance on representative sampling, sampling plans, container selection, and sampling considerations for pharmaceutical materials.

Official reference:
WHO – Guidelines for Sampling of Pharmaceutical Products and Related Materials

8.3 FDA – Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients

FDA guidance states that samples should be representative of the batch and that sampling procedures should specify the number of containers, sampling location, and sample quantity. It also emphasizes scientifically sound sampling plans and prevention of contamination.

Official reference:
FDA – Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients

8.4 FDA – Control of Components and Drug Product Containers and Closures

FDA information concerning CGMP requirements for component/raw-material sampling and testing is available through its official guidance resources.

Official reference:
FDA – CGMP Requirements for Control of Components and Drug Product Containers and Closures

8.5 Health Canada – Good Manufacturing Practices Guide

Health Canada's GMP guidance describes quality control activities including sampling, specifications, testing, documentation, and release procedures.

Official reference:
Health Canada – Good Manufacturing Practices Guide for Drug Products

9.0 Abbreviations

SOP – Standard Operating Procedure
GMP – Good Manufacturing Practice
QC/Q.C. – Quality Control
QA – Quality Assurance
API – Active Pharmaceutical Ingredient
PPE – Personal Protective Equipment
IPA – Isopropyl Alcohol
A.R. No. – Analytical Report Number
LAF – Laminar Air Flow
GDP – Good Documentation Practices

10.0 Revision History

Revision No.	Effective Date	Description of Change
00	__________	New SOP

Conclusion

A well-defined raw material sampling procedure helps maintain sample integrity, traceability, and reliable laboratory testing. The procedure should be based on an approved and scientifically justified sampling plan and should include appropriate precautions for material identity, contamination control, container selection, sample handling, labeling, and documentation.

For pharmaceutical manufacturers, sampling procedures should be integrated into the overall GMP quality system rather than treated as an isolated laboratory activity. WHO, FDA, and other regulatory authorities emphasize the importance of representative sampling, contamination control, appropriate documentation, and scientifically sound procedures.

Important: This is a general educational SOP template. It should not be adopted directly as a GMP procedure without review, site-specific risk assessment, validation/qualification requirements, and approval by the responsible QA/QC personnel.