Automation is the way of increasing quantity and quality of pharmaceutical products. M Damodar, Associate Director (IT & BPE) at Dr. Reddy’s Laboratories highlights the importance of automation in pharma plants and different steps involve
Automation of pharmaceuticals plants is the need of the hour given the increase in productivity and to ensure the supply of high quality products. The generic drug growth and spending patterns in the emerging markets has increased the demand for pharma products. At the same time creating current Good Manufacturing Practices (cGMP) and Federal Drug Authorities (FDA) approved plants which took the trend for plant automation. The debate to automate the manufacturing process began two decades ago, when, in 1990’s, the main focus was to reduce the manpower. This change for automation’s priority triggered heated arguments and negotiations with trade unions. Further, the need of manpower replacement has evolved and both categories of pharmaceutical products – prescription dosage (Rx) and Over-the-Counter (OTC) medicines have shown an increase in demand year-over-year because of the impending patent expiry for Rx and consumer awareness for OTC products. Therefore it became evident that automation would address the increase in productivity and also deliver quality products to the end customer. The pharma companies operating in the highly competitive generic market focus not only on regulatory compliance, quality and traceability but also look for reducing cost and increase inventory turns. The need of quality products is to meet the regulatory requirements of the highly regulated markets which is as per the standards of 21 CFR Part 11 that indicates, every batch produced should have digital signature and have the traceability / audit trail.
Automation in a pharma plant starts from the process of dispensing the raw material from the warehouse to packaging of the product which is the final stage for manufacturing.
Once the raw materials are received in the warehouse, they are unloaded by forklifts or through rolling conveyors which end at weighing machines in a quarantine area. Soft touch display pad recordings of the weighing machines are integrated with a printer and an ERP application so that an automated receipt is created for the material and ‘Under-test’ labels are printed for quality check. Near Infra-Red (NIR) is used for material identification and integrated with Spectrograph. The master specification of every material is maintained so that when NIR is used for identification, automatically it matches the specification, sampling procedure to results recording is managed through Laboratory Information Management System (LIMS) and finally the approved stock is moved to unrestricted use with a Barcode.
In case of tablets or capsules, manufacturing automation starts when a Batch Production Record (BPR) is generated at the initial stage of manufacturing. The material is weighed and dispensed from the raw material warehouse. It begins with an integration of weighing balance to conveyer for material transfers. The material transfers are automated through conveyer, hydraulics or by using gravity. The entire process of shifting, sewing, mixing, wet granulation, dry granulation, to the phase of granule lubrication is through this automated process. During this entire process the materials are stored in production containers which have radio frequency identification (RFID) tagged and sensors fit on to transfer systems. If taken an example of manufacturing or capsules, the next step is either tablet compression or capsule filling where in, using the feeder, this semi-finished mix/granule is loaded into the respective machinery.
The aspect of process control and monitoring these mobile production containers is through RFID technology which prevent the product mix-up between the in process batches. During the compression stage, the machines are equipped with programmable logic controllers (PLC) that can take the command for fixing batch parameters like compression pressure, RPM etc. to avoid capping. The batch parameters are so critical that each tablet compressed should have an equal Active Pharmaceutical Ingredient (API) dose. Similarly capsule filling machines also have PLCs to fix batch parameters. Again the output of this semi-finished goods is stored in mobile production containers for further processing including coating of tablets or packing the capsules. The median process of sorting the defects, capsule polishing is the subsystem of the main process. High end manufacturing suits have integrated these sub systems with the main process and built an automated plant for smooth flow of material during the manufacturing cycle. The next stage for tablets before packing is coating. Tablet coatings must be stable and strong enough to survive the handling of the tablet. It must not make tablets stick together during the coating process, and must follow the fine contours of the embossed characters or logos on tablets. Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish which makes large tablets easier to swallow. Tablet coatings are also useful to extend the shelf-life of components that are sensitive to moisture or oxidation. The coating phase is very critical where the operator has to also ensure the thickness of the tablets do not go beyond the specified limits. At the same time they must also pass the fragile test (FT) and digestion Test (DT). The entire in-process quality control is having a parallel integration with testing instruments, SCADA, Scanners, Sensors, RFID and equipment.
Once the semi-finished goods are ready for packing after going through the in-process quality protocol, they are ready for packing which could be bottle, blister or strip packing depending on the dosage and stability of the drug. Transfer of the semi-finished goods from the manufacturing area to the packing area is automated in manufacturing suits which are linked to feeders of packing machines. Once the Primary level packaging is completed the line conveyor transfers the packed material to Secondary level packaging and further it is integrated to Tertiary level packaging. To make the entire manufacturing process automation, a manufacturer has to invest in manufacturing execution system, laboratory information management system, process analytical technology, advanced process control, electronic batch record system, supply chain security system and finally integrate the entire process with enterprise resource operations management system. Such manufacturing plants will surely create the value chain along with statutory compliance, effective, efficient and show high productivity. The high level and complete automated manufacturing management systems which are typical, shown in the diagram 1.
Pharmaceutical industry will see a great need for further modernizing of its manufacturing plants when Quality by Design (QbD) will be one of the mandatory requirements of the Federal Drug Authorities. As per proposed FDA regulations, the entire process and the products need to be confirmed as per the standards of the ICH (International Conference on Harmonization) guidelines of Q8 (R2) Pharmaceutical Development, Q9 Quality Risk Management, Q10 Pharmaceutical Quality system and Q11 Development and Manufacture of Drug Substances (in progress). Currently Q8, Q9, Q10, and Q11 are the foundation for QbD and are under the regulatory framework.
Pharma Manufacturers taking road towards QbD will have future competitive advantage!