Process Control System
Basic Guidelines for Process Control System Validation
For instance, some time back, Ranbaxy received Form 483 with certain observations as a result of the US FDA inspection at its active pharmaceutical ingredients plant at Toansa in Punjab. The FDA Form 483 is issued when an investigator observes conditions that might constitute a violation of the FDA’s rules or standards. The US FDA had issued an import alert on drugs produced by Ranbaxy Laboratories at its Mohali plant in Punjab for violation of cGMP.
And against this backdrop, the drug maker remains fully committed to upholding the highest standards that patients, prescribers, regulators and all other stakeholders expect from the company by undertaking continuous improvement of its systems and processes. A company statement had admitted to past ‘shortcomings’ but stated it has rectified those and asserted that its drugs were safe and efficacious. It had also offered to co-operate fully with any regulator from anywhere in the world wanting to investigate its manufacturing practices. From these observations, it is evident that lack of proper documentation is a major cause for the issuance of Form FDA 483.
How to Deal with the FDA
A recipient of 483 should respond to the FDA, addressing each item, indicating agreement and either providing a timeline for correction or requesting clarification of what the FDA requires. This response must be submitted within 15 business days regardless of the number of observations. A good response can usually help a company avoid receiving a warning letter from the FDA, withholding of product approval, or plant shut down.
Most experts warn that responses should be comprehensive, well-reasoned, well-documented and timely, and that each observation should be addressed individually. Compliance policy guides are in place making it clear that PLC code is an electronic record. The following example of FDA warning letter explains the position that the FDA is taking on this issue – ‘Failure to establish and maintain documented procedures to control and verify the quality of product to ensure that specified design requirements are met as specified in 21CFR 820(a) (1)’. This procedure forms an integral part of process validation, which is the first step in the validation to cGMP procedure that is documented in the master validation plan.
Documentation for Validation to GMP
Procedures to control and verify the design process from PLC-based control systems to firmware to the PLC application source code must be addressed and specified clearly. Supervisory Control and Data Acquisition (SCADA) packages that often connect to PLCs count as configurable software packages. Thus, the system integrator or system supplier, in both cases, should undergo auditing in conjunction with their application of GxPs and GAMPs relative to the entire PLC/ SCADA system.