## [Quality Control Review of Regulatory Clinical Documents: The Tools of Trade and Best Practices](/blog/quality-control-review-of-regulatory-clinical-documents-the-tools-of-trade-and-best-practices) January 10, 2025 ![Quality Control Review of Regulatory Clinical Documents: The Tools of Trade and Best Practices]() 6 min read - [Medicinal Products](/blog-main-categories/medicinal-products) - [Medical Writing](/blog-main-categories/medical-writing) Quality control (QC) in the pharmaceutical industry is crucial in reviewing regulatory clinical documents to ensure the accuracy, consistency, and compliance of documents submitted to regulatory authorities for approval. ## What is a QC review? In medical writing, QC means ensuring the document’s content, style and format are of high quality. This does not just ‘happen’ but because of systematic quality control review following client-specified checklists and standard operating procedures (SOPs) to ensure a thorough and consistent review. Even well-written documents may have “Errors”, but the QC experts can spot them with a “fresh set” of eyes that a writer might overlook. Hence, a quality control check is essential before submission, because a good quality review takes time but is well worth the effort. ## Who should perform the QC review? Ideally, the QC review should be performed by somebody other than the author or medical writer of the document can be called a QC reviewer/editor, who may have less, equal, or greater experience than the author. The type of documents they might receive include: - Investigator’s brochures (IBs) - Briefing books (BBs) - Clinical study reports (CSRs)/addendums - Protocol and protocol amendments - Module 2 documents/summaries - Safety narratives - Regulatory authority responses and - Paediatric study plans etc. ## The “Tools of the Trade”: The Best practices to perform the QC  Many pharmaceutical companies or CROs have their own set of standards for producing their documents. They may be described in company-specified templates, document-specified guidelines (e.g., QC Process guideline for Clinical submission documents: Protocol, IB’s and CSR, etc), style guides, SOPs, etc. Apart from that, one must have a QC checklist to ensure that a review's quality and level of detail are consistent. A detailed QC checklist is an important tool to help the QC reviewer cover all the aspects of a review which will keep them on track of what they have checked and what’s left to do. Also, it will help them manage time efficiently. The entire QC review/editing process will follow the below sequencing steps: **1. Receiving the workflow notification from the Medical Writer:** The QC reviewer/editor will receive the request from the author (Medical Writer) with the scope of the review mentioned and the link (**to navigate the working document**) through the workflow notification generated from the respective electronic data management system’s (EDMS) eg, **MEDIVA**, **PleaseReview** or **InteliNotion,** etc. along with the source documents/links and authoring instructions (if any). **2. Confirming the required/source documents:** Get confirm the required/source documents with the Medical Writer that are available through the links shared through annotations in the document that may include: - Document current template - Source documents (Data Tables such as TLFs, Protocol and its amendments, CSR and SAP results), etc depending on the document to be reviewed. - Style guide (covering text styles, punctuation, abbreviations, capitalization, number and date formats, preferred word choice, etc). - Authoring instructions if any (covering use of company-specific authoring toolbars, cross-referencing and in-text referencing etc). - SOPs - QC checklists and attestation forms **3. Start editing the document:** Start editing the documents by “TRACK changes” ON with the below points in mind as main points of “standard QC checks” with the examples: **i. Formatting:** - Page layout - Pagination - Headers and footers **ii. Consistency:** - Synopsis/summary/conclusion versus the main body of the document: eg, Protocols - Text: study endpoints, and results eg, CSRs - Tabular data quoted in text: especially for protocols, the schedule of assessments, and study schema versus the text **iii. Tables/Figures:** - Formatting and layout - Consistency in the style of tables throughout the document (eg, Heading and Caption styles) - Clarity of presentation/legends - Ensuring the sources in the footnotes (correctly cited) and their designators have corresponding footnotes etc. **iv. References:** - Correct citations - Format of in-text citations (insert EndNote to the Reference list) - Confirming the reference list completeness **v. Internal**/**External Links:** - Internal links-confirms the internal links for the sections, In-text tables, and or figures. - External links are referenced accurately and consistently throughout the document and the blue text has been applied to the source sections/citations to external documents where a link will be created during the publishing phase of the document. **vi. General:** - Data accuracy check versus source documents/and their content - Spell check and grammar - Sentence construction - Abbreviations (client-specific if any) - Check for TOC, List of Tables/Figures and Appendices, etc. for completeness - Template verification etc. **vii. Flagging** **to the Medical Writer:** Flagging (comment alerts) issues to Medical Writer is a crucial step for maintaining document standards: Here are some of the best tips to do it effectively: 1. Tag Online to Medical Writer: Tag all comments to the Medical Writer online, which will enable them to receive mail alerts/notifications, and if you are working in a document editor like MS Word, use the track changes features or comments to highlight issues directly in the text. 2. Be Specific (easy navigation): Identify the issue. Instead of saying “There’s a mistake”, specify what the mistake is and where it’s the location (Include the section number in the source document, eg: SAP section 7.1.1). 3. Provide Context: Explain why it’s an issue. For example, “This section contradicts the data presented in the synopsis/or per the source documents like protocol”. 4. Provide Evidence-based comments: backed by relevant data, studies, or guidelines and a style guide to address the comments effectively. 5. Suggest Solutions: If possible, offer a way to fix the problem. This can help the Medical Writer understand the issue better and correct it more efficiently. 6. Be Professional and Polite: Use a respectful tone. For example, “I noticed a potential inconsistency in the text/Tables against its source documents on Page 56. Could you please review it?” 7. Prioritization of Comments: Address the critical comments first that can affect the data consistency (major), followed by less urgent ones, to manage time efficiently. 8. Summarize major issues: If there are multiple issues, provide a summary at the end of your feedback to ensure the Medical Writer understands the key areas that need further attention. 9. **Compliance Tips/Comment resolution:** Here are some tips for resolving the comments during the QC check: 1. Clarification Requests/Seek for additional information: The Medical Writer can approach the QC reviewer to seek additional information or clarification on the comment to ensure resolution. 2. Consistency Checks: Ensure that the resolution aligns with the overall document’s tone, style, and content. 3. Documentation of Changes: Document the changes made in response to comments for transparency and reference. 4. Provide Feedback loop: Implement a feedback loop where the QC reviewer/editor reviews the resolution to “confirm” satisfaction. 5. Complete the comment resolution during the QC period: Follow the client specification rules to ensure the comment resolution happens during the QC timeline provided. 6. Use automated tools: Utilize automated tools or software to track and manage comments and their resolutions for future tracking. 10. **Checklist filling and Uploading:** Ensure to fill the QC checklist (specific to each type of document) to confirm its contents like text, tables/figures appendices, etc. by ticking the boxes where the QC reviewer/editor can check off that each item in the list has been checked (**Yes**, **No** or **NA**). Also, include a comment box where the QC reviewer/editor can explain why an item is not checked and in which specific findings can be described. In addition, the checklist also has a space box that includes the version number of the document and the date of the reviewed document together with its title, project code/EDMS link, and a space to sign (**Electronic Signature)** and date the form to record that the QC has been completed. **6. Checklist Sign through DocuSign/ Adobe Acrobat** **Signature**: Once the checklist is filled, the QC reviewer will use the tools (DocuSign/Adobe Acrobat Signature) to sign the documents electronically. It helps eliminate the need for printing, signing, and scanning physical copies. Also, sending, and managing the documents digitally. **7. Check the documents back to EDMS:** After, the QC review/editing of the document is completed, **“Save”** the document with all the comments and changes **Check it** back into the respective EDMS and attach/upload the signed QC checklist (PDF) along with it. **8. In Closing:** In conclusion, when we return the reviewed copy of the document and checklist to the Medical Writer, ensure that our comments/edits are clear and easy to understand. More than just a quick read-through, QC reviews/edits are comprehensive and detailed exercises that can also be a learning experience for both the reviewer and the Medical Writer. So, overall, the regulatory agency/authority as a reader, will expect high-quality documents, but this requires an organized review process. As well as QC guidance documents, a good QC checklist will also contribute towards a review that is performed well and will improve the standard of the reviewed documents.