Working inside the quality and compliance process
A regulatory document has to satisfy the rules twice over, in what it says and in how it was produced, so the writer follows the sponsor's procedures and keeps the evidence that they were followed, and the document itself can be produced under a quality system modelled on manufacturing's.
Compliance of content and of process
The content of a document must comply with the regulations, so the ethical considerations governing how a trial will be conducted have to be reflected in the protocol. The process must comply too, because good clinical practice requires that specific steps are followed and that following them can be demonstrated. The sponsor's standard operating procedures define beforehand how a document such as a protocol will be written, who reviews it, whether an upper management group needs to be involved, and who approves it. The writer needs to follow these procedures and to have proof of having followed them, because an inspector or auditor, such as an FDA inspector, may later ask for the procedures and check whether they were followed.
Process documentation is therefore very important: it shows who reviewed the document, who approved it and whether all the steps were followed. The writer usually uploads the document to an electronic document management system, whose audit trail shows who reviewed and who approved it and can be shown to an inspector. The procedures sometimes define formal meetings that require documentation, and the minutes may need to be uploaded to a specific system.
What regulatory writing shares with manufacturing
Regulatory writing and manufacturing have many commonalities: like manufactured products, regulatory documents should be produced at a reasonable cost, completed per an agreed timeline, fit for their intended purpose, and should meet a set of corporate, legal and customer standards. Many modern manufacturing processes and principles came from the car manufacturer Toyota, and the four driving principles of the Toyota Way can also be applied to medical writing:
- Long-term philosophy: focusing on the processes used to create products or documents can help improve efficiency over time.
- Add value to the organisation by developing people and partners: in manufacturing and regulatory writing, ensuring that team members have the right skills is essential.
- The right process will produce the right results: a robust process will ensure a high-quality product.
- Continuously solving root problems drives organisational learning: manufacturers and regulatory writers should develop and maintain a system to identify root causes and quickly address issues.
A good regulatory writing practice
Manufacturers of pharmaceutical products must adhere to good manufacturing practice to mitigate risk, and a robust quality system under it includes training people, controlling starting materials and equipment, clearly defining manufacturing, packaging and storage processes, testing for quality, and documenting each step. To produce high-quality documents, the following are necessary: trained people, correct source materials that are up to date and easy to use, defined processes for the writing and review cycles, a quality control review process, and documentation of each step. A theoretical good regulatory writing practice would include the following:
- Developing the team, by ensuring that members have the proper education, relevant experience and knowledge of regulations and company policies, can help to reduce the risk of human error. Specific risks to the team can be evaluated by a gap analysis of critical skills, and cultivating a growth-mindset culture in which employees feel comfortable being noisy in their ignorance helps identify critical training needs.
- Creating a quality document profile, similar to the quality target product profile used in good manufacturing practice, verifies that the correct template, sources, interpretation and team expectations are used for the document. A storage management system prevents errors from incorrect templates, outdated data or irrelevant sources.
- Protecting the data and text by using good data hygiene and limiting review cycles prevents transcription errors, incorrect data interpretation, and inconsistent text or messages within the document. Reviewer fatigue and consistency errors can be reduced by waiting until the last review to write certain sections, such as the executive summary, synopsis, list of abbreviations and summary of changes.
- Using risk-based quality control techniques can improve efficiency and ensure that the most important areas of the document are correct. In good manufacturing practice, critical quality attributes are factors that would impact the overall quality of the product, and identifying their equivalents in a document, such as new data in an investigator's brochure, can help the reviewer prioritise where to start.
- Recording the document development process in a tracker allows the writer to confirm that all the key steps of the practice were followed and to see where improvements can be made.
- Reviewing the document development process periodically allows new risks to be addressed as they are discovered, and efficiency and quality to improve over time. Good manufacturing practice uses corrective and preventive action, a system in which root causes are identified and solutions are proposed, verified and implemented.
Identifying risks throughout regulatory document processes and finding ways to proactively mitigate them are imperative steps to creating high-quality documents. As regulations evolve and processes increase in complexity, implementing elements of a good regulatory writing practice provides a framework for long-term investment in the efficiency and quality of documents by continually improving people and processes.