Raw Material Sampling

Sampling of raw materials is essential in the bioprocessing and pharmaceutical industries for several critical reasons:

• Verification and accuracy: Determines whether the supplier's data is accurate and reliable, meeting required specifications and quality standards
• Contaminant detection: Identifies impurities or contaminants not reported in the supplier's CoA, maintaining product purity and safety
• Industry standards: Sampling is conducted in ISO Class 8 cleanrooms and samples are provided to customer for further independent testing
• Quality assurance: Maintains consistent raw material quality, reducing variability in the final product's efficacy and safety
• Risk management: Identifies and mitigates risks associated with raw material quality, particularly for critical materials
• Supplier qualification: Supports ongoing assessment and qualification of suppliers for consistent standard and supply chain reliability
• Traceability and documentation: Provides essential documentation for audits and investigations in case of quality issues or recalls
• Process optimization: Enhances understanding of raw material quality, allowing for better process control and optimization

In summary, while supplier CoAs are useful, independent sampling and testing are vital for quality, compliance, and risk management in bioprocessing.

Definition: Representative sampling involves selecting a subset of raw materials that accurately reflects the entire batch's characteristics and quality.
 

Importance:

• Accurate quality assessment: Helps ensure the sample reflects the entire batch, leading to reliable quality decisions
• Regulatory compliance: Unless otherwise specified by customer requirements, lots are sampled using ANSI Z1.4 statistical sampling techniques
• Risk mitigation: Customer receives a representative samples to verify prior to bringing on site
• Consistency: Supports uniform quality in raw materials, leading to consistent final product quality
• Efficiency: Reduces the need for extensive testing, saving time and resources

ISO 8 cleanrooms: PCS conducts raw material sampling in certified ISO 8 cleanrooms, creating a controlled environment that adheres to stringent cleanliness standards
 

Documented procedures: Sampling processes follow fully documented procedures, including gowning, cleaning, environmental monitoring, and specific customer requirements, in compliance with regulatory standards
 

Quality control and inspection: PCS employs a rigorous inspection process for raw materials, including verification against specifications, integrity checks, and contamination assessments
 

Sampling plans: Quality Control creates detailed sampling plans, specifying storage requirements, material identity information, and testing protocols
 

Reduced testing programs: For qualified raw materials, PCS adopts a risk-based approach through Reduced Testing Programs, minimizing the number of tests required for release, thus optimizing efficiency while maintaining compliance
 

Labeling: Sampled material containers are labeled to indicate sample removal, supporting traceability and proper documentation
 

Testing and release: Samples are tested either internally or by external laboratories, with results reviewed to determine if materials meet acceptance criteria. Materials are released for production based on testing outcomes and are labeled accordingly.

In summary, PCS adheres to key regulatory requirements through controlled environments, documented procedures, thorough quality control, detailed sampling plans, risk-based testing programs, and comprehensive labeling and testing protocols. These practices promote compliance, quality, and efficiency in raw material sampling.

Composite sampling: Composite sampling involves combining samples from multiple containers into a single sample for testing. This method is allowed under certain conditions:

• Homogeneous materials: Composite sampling is typically allowed when the raw materials are homogeneous, meaning they have uniform composition and characteristics throughout the batch
• Non-critical materials: It is often used for non-critical materials where slight variations between containers are not expected to impact the final product's quality
• Regulatory approval: Composite sampling must be justified and approved by regulatory authorities, so that it does not compromise the quality assessment
• Documented procedures: There must be documented procedures outlining the conditions and methods for composite sampling, enabling consistency and reliability

Individual container sampling: Individual container sampling involves taking samples from each container independently. This method is required under the following conditions:

• Critical materials: For critical materials that directly impact the final product's quality, individual container sampling is mandatory to help ensure each container meets the required specifications.
• Heterogeneous materials: When raw materials are heterogeneous, meaning they have variable composition and characteristics, individual container sampling is necessary to accurately assess the quality of each container
• Regulatory requirements: Regulatory guidelines often mandate individual container sampling for certain materials to facilitate compliance with quality and safety standards
• High-risk materials: For high-risk materials, where contamination or variability could have significant consequences, individual container sampling is required to mitigate risks

When composite sampling is disallowed:

• Non-homogeneous batches: Composite sampling is disallowed when materials are not homogeneous, as it may mask the variability between containers
• Critical and high-risk materials: For materials that are critical to the manufacturing process or pose high risks if not properly controlled, composite sampling is not permitted
• Regulatory restrictions: If regulatory guidelines specify individual container sampling for certain materials, composite sampling is not allowed

When a prior sample fails:

• Immediate re-sampling: If a prior sample fails to meet the required specifications, immediate re-sampling is necessary to confirm the initial results. This helps determine if the failure was due to sampling error, testing error, or an actual issue with the raw material.
• Root cause analysis: Conduct a root cause analysis to identify the reason for the failure. Depending on the findings, additional sampling and testing may be required to resolve the issue.
• Regulatory guidance: Follow specific regulatory guidelines and standard operating procedures (SOPs) for re-sampling in case of a failed sample to stay compliant and consistent.

Long storage periods:

• Periodic re-sampling: For materials stored over extended periods, periodic re-sampling is recommended to check for quality, potency, and safety. The frequency of re-sampling should be based on the material’s stability profile and storage conditions.
• Stability studies: Conduct stability studies to determine the appropriate re-sampling intervals. These studies assess how the material’s quality attributes change over time under specific storage conditions.
• Defined intervals: Re-sampling intervals should be clearly defined in the material’s stability protocol. Common intervals include every 6 months, annually, or as specified by the stability data.
• Environmental monitoring: Regularly monitor storage conditions (e.g., temperature, humidity) to help ensure they remain within acceptable limits. If deviations occur, re-sampling may be necessary to assess the impact on material quality.

General considerations:

• Regulatory requirements: Adhere to regulatory requirements for re-sampling frequency as specified by agencies like the FDA, EMA, WHO, and ICH.
• Material type: Consider the type of material and its susceptibility to degradation. For example, biological materials may require more frequent re-sampling compared to chemical raw materials.
• Risk management: Implement a risk-based approach to determine re-sampling frequency, considering factors such as the material’s criticality, stability, and previous quality issues.

In summary, re-sampling should occur immediately when a prior sample fails to confirm results and address potential issues. For materials in long-term storage, periodic re-sampling based on stability studies and defined intervals is essential to support ongoing quality. Adherence to regulatory requirements and a risk-based approach are critical in determining appropriate re-sampling frequencies.

Traceability:

• Unique identification: Each sample is assigned a unique identifier (e.g., barcode or QR code) that links it to the specific batch or lot of raw materials. This identifier is used throughout the sampling, testing, and storage processes.
• Comprehensive documentation: Detailed records are maintained for each sample, including information on the source batch, sampling date, personnel involved, and testing results. This documentation helps ensure that the history of each sample can be traced back to its origin.
• Electronic systems: PCS utilizes electronic systems such as Laboratory Information Management Systems (LIMS) to track samples, store data, and manage workflows. These systems provide real-time access to sample information and facilitate accurate record-keeping.

Chain-of-Custody:

• Controlled access: Access to samples is restricted to authorized personnel only. This is managed through controlled access systems and secure storage areas to prevent unauthorized handling.
• Documented transfers: Every transfer of a sample, whether for testing, storage, or further processing, is documented. This includes recording the personnel involved, date and time of transfer, and purpose of the transfer.
• Tamper-evident seals: Samples are often stored in containers with tamper-evident seals so that any unauthorized access or tampering is immediately detectable.
• Audit trails: PCS maintains audit trails that record every action taken on a sample, including who accessed it, when, and for what purpose. This promotes accountability and transparency throughout the sample’s lifecycle.

Data integrity:

• Secure data storage: Data related to samples, including test results and documentation, is stored securely in electronic systems with backup protocols to prevent data loss.
• Data validation: Regular data validation processes are in place to support the accuracy and completeness of the information recorded. This includes cross-checking data entries and automated validation checks within electronic systems.
• Access controls: Access to data is restricted based on user roles and responsibilities. Only authorized personnel can view, edit, or approve data, supporting the maintenance of data integrity.
• Compliance with guidelines: PCS adheres to regulatory guidelines such as FDA’s 21 CFR Part 11, which sets requirements for electronic records and signatures, enabling data integrity to be maintained to the highest standards.
• Training and SOPs: Personnel involved in sampling, testing, and data management are trained on standard operating procedures (SOPs) that emphasize the importance of data integrity and the correct handling of samples.

PCS maintains traceability, chain-of-custody, and data integrity for samples through the use of unique identifiers, comprehensive documentation, electronic systems, controlled access, documented transfers, tamper-evident seals, audit trails, secure data storage, data validation, access controls, compliance with regulatory guidelines, and thorough training of personnel. We follow these practices so that samples can be tracked, securely handled, and reliably documented throughout their lifecycle.