The Long Paper Trail of Documentation in API Manufacturing

Documentation – and loads of it – is essential in API manufacturing if a company wants to comply with current Good Manufacturing Practice (cGMP), and eventually seek and obtain FDA approval.

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

So why all the paperwork? It’s not only a requirement of the government, to prove that a drug will be safe and effective for patients, but it also provides a trail of best practices and a roadmap for future products for the sponsoring company and its Contract Manufacturing Organization (CMO).

For companies documenting their cGMP compliance, it helps them ensure and prove that products are consistently produced and controlled to the quality standards appropriate for their intended use. 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 product and what is being done now, to provide a basis for planning how to proceed in the future.

The Various Types of Documents Required for cGMP Compliance

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

• Quality assurance documents. Outlines the company’s own Standard Operating Procedures (SOPs) and regulations.
• SOP documentation. Provides step-by-step instructions for performing each stage in a facilities operation.
• Batch records. Outlines all the production-related tasks and activities Test method documents. Provide step-by-step instructions for testing supplies, raw materials, in process samples, final products and their corresponding tasks and activities.
• Specifications listing. Outlines what is required of a product before it can be released.
• Logbooks. Documents all core activities, such as the operation, maintenance, and calibration of equipment; or the quality of clean rooms, solution preparation, etc.

So, who is responsible for developing all of this documentation? 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.

Below are key practices CMOs and other manufacturers can take to ensure that documentation management happens more smoothly.

• Follow written procedures. Document preparation, processing, distribution and obsolescence practices need to be governed by carefully defined written procedures.
• Use multiple databases. CMOs need to have a sufficient way to control complex documentation. They should use multiple databases to control, track and cross-reference the company’s SOP, employee training records, material and manufacturing records and data. They can also be used to track Preventative Maintenance (PM), equipment calibration, deviation and quality investigations, Corrective and Preventative Actions (CAPA), change control and employee training records.
• Document batch manufacturing reviews. When batch manufacturing is complete, a quality assurance team should 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.
• 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 off the shelf tools available to do this.
• Conduct ongoing training. Finally, it’s important to conduct ongoing training of all staff to ensure continuous proper documentation practices.

Documentation is a complex and time-consuming process, but a critical element in the discovery, manufacture and delivery of drug products. The key is establishing sound processes each step of the way to meet all the regulatory requirements, cGMP guidelines and your own defined internal controls.

About the Author

Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).

Do you have questions? Talk to Ed.