Practical Risk-based Guide for Managing Data Integrity in APIs manufacturing
After defining which business processes are cGxP relevant the next phase is to map them in detail. The following steps are performed:
A. Identify the systems (both paper and electronic) involved in the processing of cGxP data
B. Define individual cGxP data elements
C. Identify cGxP data elements that can be modified, deleted, or re-processed after creation
Data Severity Assessment
A proposed approach is to use the stage of manufacturing as the primary determinant for severity classification (high-medium-low), following the principle of increasing CGxP requirements outlined in ICH Q7.
1. High / very high severity data: CGxP Data generated during and directly associated with the final stage of API synthesis
Examples:
- Temperature of final crystallisation
- Analytical testing records of API
2. Medium / medium high severity data: cGxP Data generated during and directly associated with the production of API intermediates and raw materials testing; configuration data that control the correct execution of the process, as defined in SOP or manufacturing and testing directions.
Examples:
- Reaction conditions during API intermediate production
- Records of in-process controls for API intermediate manufacture
3. Low severity data: cGxP Data that is cGxP relevant but is not directly associated with raw material testing, API intermediate production or testing or API final stage production or testing.
Examples:
- Autoclave CGxP data for waste media disposal o Operator access to production area
- cGxP data generated during the development of process or systems or equipment, prior to the validation or qualification
System Profiling
Once the system is identified, it can be further categorised based upon the cGxP data that is generated in and by the system.
Remark: please note that these categories are different from categories as defined in GAMP guide since the focus here is on the data lifecycle instead of on the system.
Category 1: A non-electronic system. No CGxP data are stored.
Category 2: An electronic system and the generated CGxP data is not stored and manually transferred on paper.
Category 3: An electronic system with some limited manual adjustable input data and the generated CGxP data is not stored but printed out.
Category 4: An electronic system with some limited manual adjustable input data and the generated CGxP data is not stored but sent via an interface to another system, e.g., a cat 5 or 6.
Category 5: An electronic system where CGxP data are permanently stored, and these CGxP data are not modified by the user to generate results (static CGxP data).
Category 6: An electronic system where CGxP data are permanently stored, and the CGxP data can be processed by the user to generate results.
Read also: GxP Topics in Pharmaceutical Industry
