Documentation in API Manufacturing: How to Manage the Tangled Web


Any company involved in the development and manufacture of Active Pharmaceutical Ingredients (APIs) and other chemical entities knows all too well about the paper trail of  documentation required for current Good Manufacturing Practice (cGMP) compliance.

Managing and controlling the extensive web of documentation required by the FDA, as well as sponsoring companies and their Contract Manufacturing Organizations (CMOs) is a job in itself and requires efficient and consistent processes.  So what exactly is required?

Current Good Manufacturing Practices

Even if you’re not going to be directly involved in documentation for and compliance of cGMP, it is a good idea to become familiar with how it works.

cGMP is the Good Housekeeping stamp of approval for quality assurance, and proves that products are consistently produced and controlled to the quality standards appropriate for their intended use. The guidelines were developed to lower the risks of things like cross contamination or false labeling which can occur in any pharmaceutical production.

cGMP regulations require that the pharmaceutical manufacturer or CMO maintains proper documentation and records, which helps to build up a detailed picture of what was done in the past regarding a specific step and what is being doing now, to provide a basis for planning how to proceed in the future.

During manufacturing site inspections, regulators spend a lot of time reviewing a company’s documents and records, so effective documentation confirms its dedication to quality controls.

If It’s Not Documented, It Never Happened

Documentation is the key to cGMP compliance, enabling traceability of all development, and manufacturing activities. Typically the head of each manufacturing department or project is the one ultimately responsible for developing, distributing, maintaining, controlling and archiving all documentation for his/her respective projects.

CMOs and other manufacturers are responsible for ensuring that all cGMP activities are performed according to the company’s clearly defined Standard Operating Procedures (SOP). Any time those SOPs change, they must be reported to management for proper implementation.  When a document has been revised, systems must be in place to ensure proper version control.

Also records must be kept at each stage of the manufacturing process so that all activities within preclinical studies, clinical trials, and the manufacture and control of products are traceable.

Documents, Documents and More Documents

cGMP-labeled manufacturing facilities must adhere to the Quality System’s requirements for design, format and organization. To ensure that this is accomplished, below are some of the most common types of documents that are required:

  1. Quality assurance documents. Outline the company’s own SOPs and regulations.
  2. SOP Documentation.  Provide step-by-step instructions for performing each stage in the manufacturing process.
  3. Batch records. Outline production-related tasks and activities.
  4. Test methods documents. Provide step-by-step instructions for testing supplies, materials and the corresponding tasks and activities.
  5. Specifications listing. Outlines what is required of a product before it can be released.
  6. Logbooks: Document all core activities, such as the operation, maintenance, and calibration of equipment; or the quality of clean rooms, solution preparation, etc.

While it’s clear that documentation is a time-consuming and complex requirement for any cGMP facility, below are key practices CMOs and other manufacturers can take to ensure it happens more smoothly.

  1. Use multiple databases. CMOs need to have a sufficient way to control the complex web of documentation. At PCI Synthesis, we use multiple databases to control, track and cross-reference the company’s SOP, employee training records, material and manufacturing records and data.  They are also used to track Preventative Maintenance (PM), equipment calibration, deviation and quality investigations, Corrective and Preventative Actions (CAPA), change control and employee training records.
  2. Follow written procedures. Document preparation, processing, distribution and obsolescence practices need to be governed by carefully defined written procedures.
  3. Document batch manufacturing reviews. When batch manufacturing is complete, a quality assurance team must review and reconcile all issued documentation to ensure the information is properly recorded.  It also should reconcile all issued documentation to ensure the information is complete, after which they can securely archive the documentation.
  4. Scan documentation. As an added measure, and to allow for rapid retrieval of information, all original data and documentation should be scanned into a digital format, and there are a number of tools available off-the-shelf that support this function.
  5. Conduct ongoing training. Finally, it’s important to conduct ongoing training of staff to ensure continuous proper documentation practices.

Documentation is a necessary evil when it comes to cGMP pharmaceutical manufacturing. Yet sound SOPs and best practices to ensure proper management and control of required documents can go a long way to ensure successful commercialization of safe and effective APIs and other chemical entities – the ultimate goal of any pharmaceutical firm.