Clinical Researcher—October 2023 (Volume 37, Issue 5)
CULTIVATING QUALITY
Olena Chervonenko, MS
Standard operating procedures (SOPs) play a vital role in ensuring quality, compliance, and safety across a pharmaceutical company’s operations. SOPs are key to ensuring users follow current requirements and best practices and perform tasks consistently and uniformly.
An SOP is a documented set of step-by-step instructions that outline the approved methods and practices for carrying out specific tasks or processes within an organization.
When writing SOPs, it’s important to strike the right balance between providing enough detail and avoiding excessive complexity. Insufficient detail increases the likelihood of users improvising on the spot or following widely used, but perhaps inadequate, methods. On the other hand, excessive information can lead to confusion, errors, and mistakes.
In the pharmaceutical industry, improvising or deviating from established methods can have serious consequences and may result in the company becoming noncompliant with one or more of the internationally agreed-upon “Good x Practices,” where “x” may stand for Clinical,{1} Manufacturing,{2} Laboratory,{3} etc.
SOPs must ensure the robustness, traceability, and integrity of a Pharmaceutical Quality System (PQS) of an organization and contribute to maintaining quality, safety, and compliance standards within the organization.
Robustness of the PQS
SOPs provide a systematic and documented approach to performing critical tasks and processes within an organization. By outlining specific procedures, controls, and requirements, SOPs help ensure the robustness of the PQS. They establish a framework that promotes consistency, traceability, and accountability in all operations.
SOPs incorporate safety considerations and guidelines to mitigate risks and protect personnel, patients, and the environment. They outline business workflows, safety protocols, personal protective equipment requirements, handling procedures for hazardous substances, and emergency response measures. By adhering to SOPs, organizations promote a culture of safety and minimize the potential for accidents or incidents.
In short, SOPs are essential tools in assuring the robustness of the PQS.
Traceability
Ensuring the traceability of the PQS is a critical aspect of SOPs within the pharmaceutical industry. Traceability provides a clear and documented path that demonstrates the implementation and effectiveness of the PQS. Here are some key considerations to incorporate traceability into your SOPs:
Documented References: SOPs should reference the relevant sections of the PQS documentation, such as quality manuals, policies, and guidelines. This ensures that SOPs are aligned with the overall quality system and current edition of guides.
Version Control: SOPs should have a version control system in place, indicating the specific version number, date of revision, and any relevant updates. This allows for easy identification of the most current version and facilitates traceability.
Cross-Referencing: SOPs should cross-reference other related SOPs or documents within the PQS. This ensures that interdependencies between procedures are clearly identified and maintained.
Change Control Process: The revision history of an SOP should clearly outline the specific changes that were made, accompanied by a linked change control document. This document should include thorough documentation of any modifications to the SOPs, along with justification and, if applicable, a risk assessment. This facilitates traceability and identification of the chronology of changes.
By incorporating these traceability elements into your SOPs, you establish a clear link between the procedures outlined in the SOPs and the overall PQS, ensuring transparency, compliance, and effective quality management.
Data Integrity
Data integrity is a critical aspect of SOPs within the pharmaceutical industry. It ensures that data generated, recorded, and reported during operations are accurate, complete, and reliable. SOPs must declare data integrity principles to prevent data manipulation, fraud, and errors. Key considerations for maintaining data integrity via SOPs include:
Data Recording: SOPs should outline the proper methods for recording data accurately, including clear instructions on data entry, identification, and verification.
Audit Trails: SOPs should define procedures for creating and maintaining audit trails, which provide a chronological record of data changes, ensuring data integrity and traceability.
Data Security: SOPs should incorporate measures to protect data integrity, such as access controls, data encryption, and regular data backups.
Bringing in the Right People
It is important to involve quality assurance (QA) and senior management in all stages of SOP creation—from ideation to assessing the effectiveness of implemented SOPs.
The QA department plays a crucial role in ensuring the effectiveness of SOPs within the pharmaceutical industry. QA staff are responsible for overseeing the development, implementation, and maintenance of SOPs to guarantee compliance with industry regulations and standards. Chiefly, they are responsible for SOP review, collaborating with subject matter experts to ensure SOPs are accurate, comprehensive, and aligned with regulatory requirements.
Senior management plays a key role in supporting and driving the effective implementation of SOPs. Their responsibilities include:
Policy and Strategy: Establishing clear policies and strategies that emphasize the importance of SOPs in ensuring quality, safety, and compliance throughout the organization.
Leadership and Communication: Promoting a culture of quality and compliance, fostering a shared understanding of the significance of SOPs at all levels of the organization. Senior management also communicates expectations, provides guidance, and encourages employee engagement.
Continuous Improvement: Supporting a continuous improvement mindset by encouraging feedback, monitoring of performance metrics, and implementing initiatives to enhance SOP effectiveness.
Focus of Inspection
During inspections, regulatory authorities and auditors focus on evaluating the implementation and effectiveness of SOPs. They assess whether the organization has well-documented and controlled SOPs, that these SOPs are followed, and that they are in compliance with regulatory requirements. Key areas of inspections related to SOPs include:
Process Description: Inspectors assess whether the organization has cohesively documented all GxP relevant activities.
SOP Availability: Inspectors verify that SOPs are readily available to personnel and accessible in relevant areas where tasks are performed.
Adherence to SOPs: Inspectors assess whether employees follow SOPs consistently, ensuring that documented procedures are being executed as specified.
Further Considerations
When creating or updating SOPs, it is important to keep in mind the following points to avoid unnecessary complexity:
Author and Reviewer: The author of the procedure should be someone who performs the task or possesses a deep understanding of it. They should strike a balance between providing adequate detail and avoiding excessive elaboration. The reviewer’s role is to ensure that the SOP achieves the appropriate level of detail.
Ask Why: Simplify and improve the workflow by questioning the necessity of each step in the SOP. This technique involves creating a comprehensive list of all the steps in a work process and critically evaluating their purpose.
Field Testing: Red line the procedure in the field to assess its relevance and coherence. This practice involves documenting and accurately recording the process while onsite, often accompanied by clear photos that can be included in the SOP.
Embrace Simplicity: Lengthy and intricate SOPs are challenging to follow. Strive to keep SOPs simple and user-friendly while ensuring that all important steps are included. Complex tasks can be broken down into smaller sub-steps. Sentences should generally be kept short to ensure clarity.
Visual Aids: Humans process visual information more easily than text. Improve the understandability of SOPs by incorporating photos, drawings, and flowcharts. Visual aids can significantly assist in conveying complex information.
Minimize Involvement: Involving fewer individuals in a task reduces the likelihood of human error. Streamlining the number of people involved in a task enhances efficiency and accuracy.
Audience Consideration: SOPs should be tailored to the education, experience, knowledge, and abilities of the personnel who will use them.
Language: SOPs should be written using vocabulary relevant to the area of use, experience, knowledge, and abilities of the personnel who will use them.
Testing and Verification: Before finalizing an SOP, conduct tests with individuals who will use it regularly. Their feedback can help identify unclear information, missing steps, or incorrect sequencing. It can also be beneficial to have someone with limited knowledge of the process test the SOP to ensure its accessibility to a broader audience.
Preserve Simplification Efforts: During the review process, carefully evaluate any additional or removed steps. Justification should be provided before incorporating any changes, being cautious to maintain the simplified nature of the SOP. This approach ensures that deviations are properly identified through root cause analysis.
Regular Review and Revision: Seek feedback from those who have direct experience using the SOP after several weeks of implementation. Evaluate clarity, effectiveness, readability, and ease of use. Revise the SOP based on the feedback received.
Keep SOPs Updated: Regularly review and update SOPs to align with current practices and requirements. Failure to periodically review and update SOPs can quickly render them obsolete. A recommended review frequency is every two to three years. The review frequency should be justified.
Conclusion
By following these guidelines and incorporating the necessary elements, SOPs can effectively guide pharmaceutical industry professionals, promote efficiency, support compliance and data integrity, and contribute to the overall success of an organization.
References
- Good clinical practice (GCP) E6(R3), ICH. https://database.ich.org/sites/default/files/ICH_E6%28R3%29_DraftGuideline_2023_0519.pdf
- Good manufacturing practice, EMA. https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-manufacturing-practice
- OECD Series on Principles of Good Laboratory Practice (GLP) and Compliance Monitoring, OECD. https://www.oecd.org/chemicalsafety/testing/oecdseriesonprinciplesofgoodlaboratorypracticeglpandcompliancemonitoring.htm
Resources
A list of SOPs required by the U.S. Food and Drug Administration, the European Union Guideline to Good Manufacturing Practice (GMP), and the World Health Organization for GMP activities can be found at http://www.gmp-compliance.org/gmp-news/which-sops-are-required-by-gmp.
For Good Documentation Practice (GDP), the Health Products Regulatory Authority in Ireland has published a guidance document that includes the SOPs that are needed for compliance with GDP and details the general framework for each SOP at https://www.hpra.ie/docs/default-source/publications-forms/guidance-documents/ia-g0038-guide-to-quality-system-for-general-sale-wholesale-distributors-v2.pdf?sfvrsn=14.
European Medicines Agency Procedures, EMA: https://www.ema.europa.eu/en/procedures
Manual of Policies and Procedures, FDA: https://www.fda.gov/media/90280/download
The contents of this article are solely the opinion of the author and do not represent the opinions of PharmaLex GmbH or its parent Cencora Inc. PharmaLex and Cencora strongly encourage readers to review the references provided with this article and all available information related to the topics mentioned herein and to rely on their own experience and expertise in making decisions related thereto.
Olena Chervonenko, MS, (Olena.Chervonenko@pharmalex.com) is Associate Director of Quality Management and Compliance for PharmaLex. She has a strong background in pharmaceutical chemistry and quality management.
