GMP API Process Validation


If you have questions about GMP API Process Validation, please contact us

These regulations, which have the force of law, require that manufacturers, processors, and packagers of drugs, medical devices, food, and blood products take proactive steps to ensure that their products are safe, pure, and effective. GMP regulations require a quality approach to manufacturing, enabling companies to minimize or eliminate instances of contamination, mix ups, and errors. This, in turn, protects the consumer from purchasing a product that is not effective or even worse, dangerous.

GMP is also sometimes referred to as “cGMP.” The “c” stands for “current,” reminding manufacturers that they must employ technologies and systems which are up-to-date in order to comply with the regulation. Systems and equipment used to prevent contamination, mix-ups, and errors, which may have been “top-of-the-line” 20 years ago, may be less than adequate or considered obsolete by today’s standards.

At PCI Synthesis, we strive to be “top-of-the-line” today and into the future by following all cGMP Regulations as documented in 21CFR211 which require facilities to perform rigorous IQ (installation qualifications), OQ (operational qualifications), and PQ (performance qualifications) on all their manufacturing equipment and facilities. Our commercial manufacturing suite (reactor suite pictured above) where we produce our API’s has gone through the IQ, OQ, PQ qualification process by following and complying with all FDA cGMP standards. The equipment in this suite includes an Inconel 1400 gallon reactor, a Hastelloy 1000 gallon reactor, and a Guedu 2 m2, Hastalloy Pressure Neutsche Filter.

During the IQ, each piece of plant equipment as well as all critical instruments are listed and calibrated. The equipment is checked for proper process and utility piping connections and material of construction. Electrical hook ups are checked to ensure proper and correct connections. Reactor specifications including materials of construction, piping and gasket types are all verified. Each condenser is checked and verified to ensure that the proper installation of process, utility piping connections, materials of construction and gasket types have properly taken place.

During the OQ, each piece of equipment is cycled through two heating and cooling cycles. The heat up and cool down time will be documented as the baseline. Operational checks of the pressure and temperature recording instrumentation are then conducted. Response time of the instrumentation will also be documented. Reactor agitators are cycled through their range of operation to ensure proper operation and repeatability.

SOP’s (standard operating procedures) are written for the proper operation of the equipment, including location of valves, and their normal operating positions. The sequence of valve operations to perform various operations such as filtering, back flushing, venting, etc. will be documented, verified and executed.

For each product to be produced/handled in a particular reactor, a PQ protocol is first written and then validated. This protocol will include all the procedures to be used to ensure the reactor is clean and able to perform the processes required.

During the PQ, all equipment cleaning procedures and process procedures are validated and documented. The results of the protocol are used to prepare the SOPs for operating the equipment. Additionally, the PQ protocol and results are incorporated into cleaning SOP’s to ensure validated cleaning takes place between batches of different production campaigns. Special attention to cleaning procedures takes place between product changeovers for obvious reasons.

The entire IQ,OQ, and PQ process is time consuming and requires significant internal resources. Engineering, maintenance, and production personnel all work together to generate and execute all the necessary protocols. The result of all this effort is the reduction of processing upsets, product impurities (cross contamination) from process to process, and ultimately consistent manufacturing from batch to batch. This is all a fundamental part of being a cGMP, FDA inspected and compliant facility. Following these protocols and all the other cGMP guidelines ensures that we can reliably produce all of our API products. Our valued customers can be assured that their API material – whether it is a commercial product or a developmental material, is being produced to the highest standards possible.