Sampling in Pharmaceutical Manufacturing: Safety, Strategy, and Best Practices

Pharmaceutical manufacturing requires sampling as an essential procedure which maintains product quality and product consistency. The article provides essential guidelines for performing safe effective sampling which includes safety requirements and different strategies and procedural steps for different product types.

Sampling Safety Considerations:

Health and safety protocols of the company along with COSHH assessments need to guide all sampling operations. All drug substance and excipient sampling requires access to the proper safety assessment which specifies necessary handling procedures.  Diverse materials that present hazardous qualities need both bulk substance protection along with proper sealing of containers and sampling points.

Materials exposed to sampling operations present hazards that endanger samplers by harming their bodies or through fires and explosions.  Any newly discovered substance comes with multiple potential hazards so sampling personnel should treat every substance as hazardous unless validated otherwise. Customers can use Material Safety Data Sheets (MSDS) to find proper guidelines for working with dangerous chemicals.

Sampling Facilities Considerations:

A sampling facility should have measures to stop contamination of opened containers and samples and operators while also avoiding contamination from product or environmental sources. Aerosol valves together with sterile cephalosporin powders need specialized production premises for sampling purposes.

Customarily sampling should take place at contained testing spots designed specifically for the task.  It becomes impractical to implement this approach to sampling when intervention requires direct line extraction of in-process control materials.  The sampling staff needs to have unhindered access across all areas in which sampling takes place. Adequate light and ventilation requirements together with safety standards and sample-specific needs serve as guidelines for arranging the storage space.  The necessary measures need to be implemented to stop stacked containers and bulk solids from collapsing.

The sampled material determines acceptable selection criteria for all sampling equipment together with tools and containers.  The sampling equipment along with its containers must be clean along with being disposable whenever possible.  Reused sampling equipment needs proper cleaning from one use to the next followed by complete drying procedures.

Warning appliances located in the sampling area need to be known along with the operation procedure for fire extinguishers and protective goggles by personnel who sample materials.  The sampler must wear suitable clothing consisting of cotton overalls but should avoid nylon materials to prevent electrostatic charges.  A sampling area must exist without any possible ignition elements.

GMP and Sampling:

The exact collection method matters not but the obtained sample needs to demonstrate that it represents the contents from the vessel or container.  The responsible sampler along with the laboratory supervisor need to establish an approved sampling strategy before execution.  A strategy should include all service provider responsibilities and provide the required documents such as forms for sample requests and results reporting while presentation of sampling points.

The sampling plan should include information regarding sample quantity and numbers while specifying locations and vessel number along with subdivision procedures and selection of sampling devices and proper labeling techniques for containers.  The assessment for API safety needs to have its own section within health protocols. Information regarding storage and shipping should be included when needed together with necessary retention sample provisions and specifications for special reporting requirements.

Medicines must be utilized to decrease factors that cause sample separation specifically affecting non-homogeneous powder mixes and ensure contamination-free sampling occurs in a clean space. The identification process should include proper labeling for all sampling containers while immediate containerizations of both bulk and sample products should occur to avoid contamination between containers. A modification in the sampling plan demands strict adherence to change control procedures which require scientific evidence for approval.

Number of Samples and Sampling Locations:

A proper sampling methodology should consist of enough sample quantities together with enough testing sessions to achieve a sufficient opportunity of finding minor defects with a strong chance to find major defects.  A wrong sample size leads to either unproductive work or more seriously poses the risk of major defect undetectability which threatens patient safety.

The worldwide accepted sampling methods BS6001: Part 1: 1999, ISO2859-1 and ANSI/ASQC Z1.4-1993 provide the foundation for medical device CV validation. A sampling program requires the definition of inspection level and Acceptable Quality Level (AQL) prior to sample collection. Both the sample number and placement must receive documented justification when inspecting any sample type.  Follow these guidelines when documentation of rationale is unavailable since they supplement sampling requirements.

1 Powder Blends and Granules:

A suitable thief should be used for obtaining at least three blend samples from each measurement area.  The sampling plan defines whether you should divide the collected samples because individual portions might produce wrong results due to segregation effects.  Sample preparation should use complete transfer of the sampling container contents because weight errors and powder segregation impairment should be avoided. The weight of one dose unit should range between one time to three times for each individual sample.

Ten relevant points should be selected for sampling across each blender unit and sample retrieval will happen at top and bottom ranges together with the middle and center area and edge position. All chosen sampling points need documentation based on their selection reasoning. Blend sample site selection depends on equipment dimensions as well as geometry and manufacturing process along with formulation requirements and knowledge from existing experience. The worst-case areas where blend uniformity is most likely to be compromised should be included in the selection process.

2 Tablets and Capsules:

For release testing purposes one needs to grab a stratified sample from capsules and uncoated tablets. The batch needs to have sampling procedures conducted at three specified points: beginning, end and periodic intervals throughout production. Samples of coated tablets can directly come from coating pans or bulk containers because the tablet randomization process during coating operations ensures natural distribution.

3 Liquid and Topical Products in Bulk Containers:

Samples for most situations should be obtained as directly centered within the holding receptor but homogeneity investigations require samples at the top and bottom as well as the middle. When taking samples of suspensions mechanical stirring should be preferred and used for movement during the sampling process.

4 In-Process Control Samples:

You should obtain suitable numbers of dosage units from different and equally spaced time intervals to confirm uniformity during manufacturing operations.  The general practice involves collecting at least 20 items as test samples. The storage of samples requires polyethylene bags for immediate testing but amber glass bottles should be used for prolonged storage needs.

5 Release Testing:

The testing protocol for randomized lots requires random selection of at least 20 items while preferably using √(n+1) containers (where n represents the container count) evenly spread across the total area. The testing for complete triplicate analysis requires adequate number of items. Polyethylene bags function well in finished product packaging as the bulk storage requires amber glass bottles.

6 Keeping Samples:

Random sampling of usually 20 items should be conducted properly. The testing requirements need a sufficient number of items that enable triplicates or duplicates. The final packaging of finished products should use polyethylene bags as the main container but bulk product should receive storage within amber glass bottles.

7 Samples from Market Returns:

Take at least 20 items randomly. The experimental unit needs to provide enough samples for triple repetition of all tests. Polyethylene bags serve as appropriate material for storing samples.

8 Active Pharmaceutical Ingredients (APIs):

In case no specific direction exists retrieve the sample from under each container surface. The selected sample container needs to have dimensions that reduce airspace inside the container. For physical testing of particle size analysis there is no valid reason to perform sub-sampling. Most storage purposes benefit from the use of amber glass bottles.

9 Packaging Materials:

Select a random sample number that is adequate. The sampling procedure includes √(n+1) samples from n items within the lot unless the protocol specifically comes with alternative instructions. Storage of samples in polyethylene bags commonly works well under such conditions.## Sampling in Pharmaceutical Manufacturing: Safety, Strategy, and Best Practices

Pharmaceutical manufacturing requires sampling as an essential procedure which maintains product quality and product consistency. The article provides essential guidelines for performing safe effective sampling which includes safety requirements and different strategies and procedural steps for different product types.