During a recent plant visit to Lupin’s Nagpur facility, Swati Rana in an interaction with Rajiv Desai, Executive VP – Corporate Quality, Lupin and Alok Ghosh, President – Technical Operations, Lupin, finds out about the latest technology and innovation implemented in the plant to make it future ready for the generic market
Seeing an immense potential for growth of generic market in India, Lupin’s Nagpur facility is completely ready to compete and cater to the demands of generic drugs globally. The facility will be the largest with highest manufacturing capacity post its commercialisation. The plant manufactures both oral solid dosage (OSD) and injectables. Lupin has invested `753.12 crore in the plant, out of which `488.79 crore has been invested in OSD and `264.33 crore in injectables. The plant has completed four US FDA inspections, three inspections for product approvals and one on GMP compliance with zero observation. It is well equipped with latest technology and has error free documentation. The plant is expected to be fully operational from April 2019. Express Pharma tries to understand from Alok Ghosh, President – Technical Operations, Lupin and Rajiv Desai, Executive VP – Corporate Quality, Lupin, what makes this plant unique and different from its other plants.
The company has looked after three essential parts i.e. compliance, cost and supply chain before designing the plant and made the plant future ready to deal with challenges in the generic market. Ghosh, while explaining the need to focus on these three parts says, “There are three essential parts that I look into, first is the compliance and when I talk about compliance it’s not the FDA alone but also environment safety. Next is cost focus. We are in a generic market and if we are not cost competitive and better than others in the market, we just can’t survive. The third being supply chain which is where we need to maintain our supply chain to deliver the products on time in markets. So, looking at all these things, we have set up this plant. Going forward, the generic market would not be as easy as it looks and we want to keep ourselves ready and we should be able to compete in the market.”
Compliance challenges
The facility aims to meet regulatory expectations and compliance challenges with its latest technologies, automation, innovation and less human intervention. Desai gave a brief understanding on the issues faced during FDA inspection. He says, “Since we are into a highly regulated market, our sites get inspected on a regular basis. All our sites goes through FDA inspection every year. That’s the kind of audit frequency we face. Every year the audit expectation is different. Even if the products are old, the expectation of FDA are changing, so we have to gear up for that. Every couple of years, FDA comes out with new theme, one time it was data integrity, other time it was more of 21 CFR i.e. compliance, etc. so we have being trying to meet the FDA’s expectations.”
Speaking on the current expectations of FDA inspectors, he further says, “The expectation of FDA nowadays is that they want to interact more to the people on site, as they are the one working day in and out on the site, analysing products. If they are the people on the site, they should be able to talk confidently to the inspectors. We give that confidence to our people by allowing them to do their work correctly without being biased or without any apprehensions. The FDA inspectors are trained to inspect, they are trained for understanding body language, and face reading. So if someone is bluffing, it shows up in their gesture, that’s where they get caught. For us there is no issue, we have created a friendly environment in the company and we try to nurture confidence in our employers working at any level in the company.”
To deal with the current expectations of FDA, the company also recruits their employees carefully and train them to maintain the organisational culture and attitude. It has a dedicated technical training cell at Lonavala near Mumbai for organisational induction and other training. Desai says, “We are very careful in recruiting, we see what kind of experience and attitude they carry because that’s how the culture comes in. We have to ensure that the same culture is maintained. We might have nurtured a good culture with the existing set of people, but if somebody comes from outside, if that person influences the way of working, brings in over smartness in work, then we don’t need them. We have a simple way of working and we want to go ahead with that. So, we have to be alert about such kind of people and try to make sure that attritions are low, give them the confidence and space of working. That’s a big challenge.”
About the plant
The Nagpur plant of Lupin is spread over total plot area of 1,073,557 sq. ft with dedicated units for OSD and injectable manufacturing. The facility has two blocks for OSD and one for injectable. The total build up area of block 1 is 1,17,394 sq.ft, block 2 is 4,63,131Sq.ft and injectable unit is 1,30,378 sq. ft. Like any other drug manufacturing plants, all the units of this facility have manufacturing area, packing area (primary + secondary) and quality control area. The plant is large in volume and well equipped with largest available capacity equipment.
OSD
The OSD unit in the facility has closed process materials handling, separate floor for uncleaned/ cleaned equipment with automatic washing to reduce the contamination, dedicated AHU for each process area and automatic weighing and dispensing for all input materials with a total storage capacity of 7080 pallets.
“As this is a formulation plant, we don’t have any effluent generated here. Even if some waste is generated, this is a zero discharge plant. We don’t discharge the waste outside, we recycle them in any possible manner. In terms of the safety to people, we ensure that the safety is maintained and the risk is minimal,” informs Desai. The company has also taken care of environment health and safety by having double door emergency exit for each process area, fire protection systems: dedicated for fire hydrant and sprinkler, fire detection systems: Duct detectors, fire alarms & PAS system and zero waste water discharge.
The manufacturing process operates with PLC / HMI, e.g. for rapid mixer granulator, fluid bed dryer, coating pans, capsule filing machines, bulk filling lines and blister machines. Quality control lab in the OSD unit is equipped with all sophisticated modern analytical instruments such as HPLC, HS-GC and Particle size analyser.
Injectables
The injectable unit manufactures prefilled syringes, injectable vial filling – liquid as well as lyophilised vials. All aseptic filling are handled in isolators. The company has installed an online system for monitoring of viable and non-viable particles and automatic loading and unloading system. The machines in injectable units consist of liquid line of vial washing machine, depyrogenation tunnel, vial filling machine, lyophilizer (10 Sq. Meter) and sealing machine.
Microbiology lab is equipped with sophisticated modern equipment such as sterility test isolator, Vitek 2 compact, steam; steriliser, LAF, biosafety cabinet and incubators. Bioburden testing, water testing, endotoxin testing, sterility testing and all advanced testing available in pharmaceutical industries are tested in the lab here.
Error free documentation
The USP of Nagpur facility that makes it different from the rest of its plant is error-free documentation. Electronic Batch Records Management System, which is being actively implemented in the Nagpur plant, will minimise the manual intervention in the work processes and human errors in the documentation. eBPR: Electronic Batch Records Management System maintains paperless electronic manufacturing records with a minimal manual intervention. The equipment captures process critical data online from sophisticated equipment directly into batch manufacturing record.
The company has installed MODA: a software for paperless QC Micro data collection and management (Environment Monitoring, utility, and product testing). The software easily integrates with commonly used instrumentation and media found in manufacturing facilities, specifically production and laboratory areas. It delivers timely and accurate QC monitoring by utilising location-based scheduling, mobile data collection, and paperless lab processing. It is integrated with Laboratory Information Management Systems (LIMS) to bridge the communication gap between QC and production.
Once the facility is fully operational and the latest technologies works well, the other plants of Lupin might also go through the tech transfer for better productivity.