The Paper Trail of API Manufacturing Can Be a Long and Winding Road

Good Manufacturing Practices (GMP) is central to quality assurance in API manufacturing, ensuring that products are consistently manufactured to the quality standards relevant to their intended use. GMP can help to reduce much of the risk involved with drug development and ensures proof of all development, manufacturing, and testing activities. The GMP guidelines were developed to lower the risks of things like cross contamination or false labeling which can occur in any pharmaceutical production and the results can be devastating.

Documentation is the key to GMP 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.

When inspecting a plant, FDA inspectors spend a lot of time reviewing an API manufacturer’s documents. For this reason, 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. Yet, not only is it a requirement to have up-to-date documentation, but it also can help to inform future projects, by providing a paper trail of previous related activities.

But maintaining proper documentation is not easy. Contract development & Manufacturing Organizations (CDMOs) and other manufacturers are responsible for ensuring that all GMP activities are performed according to the company’s clearly defined Standard Operating Procedures (SOPs). Any time those SOPs change, they must be reported to management for documentation.  And when a document has been revised, systems must be in place to ensure proper version control. And, it’s not just for a handful of document types, but many.

The Many Types of API Manufacturing Documentation

Documentation involves more than you think in API manufacturing. Basically, for every step in the process, a type of documentation is required.  Below are six of the key types of documentation required in API manufacturing, and the list could go on further:

• Quality Assurance (QA) documents. Which outline the company’s own SOPs and regulations.
• Standard Operating Procedures. To provide step-by-step instructions for performing each stage in the manufacturing process.
• Batch records. Identifying all production-related tasks and activities
• Test methods documents. Providing step-by-step instructions for testing supplies, materials and the corresponding tasks and activities. 
• Specifications listing. Establishing the criteria to which a substance should conform to be considered acceptable Specifications can includes a list of tests, references to analytical procedures and acceptance criteria for the tests described.
• Log books. Documenting all core activities, such as the operation, maintenance, and calibration of equipment; or the quality of clean rooms.

Best Practices for Documentation Management and Control

Documentation can be an arduous process, but without it, all of your achievements could be for nothing. Below are six best practices that can go a long way to helping you meet your documentation objectives.

1. Cross-reference SOPs with multiple databases. At Seqens CDMO NA, we use multiple databases to control, track and cross-reference our Standard Operating Procedures,  employee training records, material and manufacturing records and data and other documents. 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. Clearly outline documentation procedures. Document preparation, processing, and distribution procedures need to be carefully standardized and articulated to ensure consistency across departments.
3. Provide oversight of batch manufacturing reviews. When batch manufacturing is complete, a quality assurance team member 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.
4. Digitize the 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, if not originally created in that form.There are a number of tools available off-the-shelf that support this function.  
5. Establish the importance of documentation. Effectively documenting critical actions, processes and results can sound less than exciting after creating a revolutionary API. It’s important, however, that the importance of accurate and consistent documentation be communicated from the leadership on down.
6. Provide ongoing training. Once successful documentation SOPs and processes are put in place, there should be ongoing training provided to staff to keep pace with changing regulations and shifting company strategies.

The importance of effective documentation in API manufacturing can’t be stressed enough. Having effectives processes in place to ensure that vital data is protected can help to avoid any setbacks in the approval process, as well as miscommunication among the team and sponsor. There’s a famous quote that reads, “if it is not documented, it did not happen.” Documentation validates your hard work and efforts.

For more insights, check out Passing the Baton in API Development; The Many Reasons to Choose an Integrated CDMO; or Scaling UP API Manufacturing.