Vincent Colicchio is vice president of supply chain and external manufacturing for Dr. Reddy’s Laboratories North America. In this interview he discusses optimizing the industry’s workforce, facilities and processes, including measures to avoid drug shortages.
CDR: What do you see as workforce needs and training for generic drug manufacturing?
COLICCHIO: For generic drug manufacturing, there are distinct types of workforce training that need to be factored into the full scope. When you look at the workforce, it’s not only manufacturing operations training, but it’s the different cross-functional groups that play key roles including, but not limited to, packaging, engineering, technical services, maintenance, metrology, facilities, quality assurance, quality control, warehouse, distribution, etc. Universally speaking, workforce training is a dynamic requirement that impacts several groups to support or perform generic drug manufacturing. Let me list these and expand upon them as well.
The key part of pharmaceutical manufacturing training would be training in pharmaceutical technology and unit operations, and this would apply for any type of pharma manufacturing technology. Whether it’s for oral solid dosage, topicals, oral liquids, injectables, transdermals or combination products (e.g., medical device and drug product), the manufacturing teams require a strong understanding of manufacturing technology and unit operations. The technologies are unique, so you need to have extraordinarily strong training and abilities to perform these kinds of production operations.
The next part of this would also be current Good Manufacturing Practices (cGMP). It is the fundamental of any aspect of pharma manufacturing. Also, another key training element would be Good Documentation Practices (GDP). And, with most companies, annual training is conducted for cGMP and GDP. People also need to have a thorough understanding of the manufacturing and packaging batch records so they can accurately perform the process steps during production according to the batch record instructions, document the entries correctly free of errors, and complete product yield reconciliations to close out the batch records. This supports a higher proportion of first-time right results, and it leads towards on-time processing of batch records. GDP training enables this to happen.
Another part of the training is for adherence to Standard Operating Procedures (SOPs) and associated forms. SOPs are fundamental to the training program for any pharma manufacturer. When we look at unit operations, these are specifically tied to the manufacturing, packaging processes and overall production equipment operations. For example, for oral solid dosage production, this would include dispensing; milling; wet and dry granulation; fluid bed drying; coating operations in a fluidized bed; tablet compression, pan coating, encapsulation; and bottle and blister packaging. For topicals, oral liquids and nasal spray production, this would include dispensing; compounding; and filling tubes, bottles, jars and nasal spray containers. For transdermals production, this would include dispensing, compounding or mass preparation, slitting and pouching, and cartoning. Of course, these pharma processes will also require vision system inspections, check weighing and other means of inspection throughout the production processes. Serialization is also included in the packaging operation. So, these are just examples of the some of the types of unit operations that operators, maintenance, engineers, and other pharma professionals need to train on and master over time to meet their job responsibilities. Another aspect of workforce training must be careful attention to production batch records, documentation and labeling in order to control operations to result in first-time right production and to avoid product mix-ups. The key is to follow the SOPs and batch record instructions through the course of the work. Steadfast adherence to the SOPs and batch records will ensure consistency in execution of the manufacturing processes to ensure patient safety and avoid product recalls.
CDR: How important is scientific/medical knowledge?
COLICCHIO: It is critical that there must be a thorough understanding of the product, the process, and the therapy or indications. It is important that pharma professionals understand their product and how the product is manufactured. They need to understand the process since this is critical to ensuring that you conduct first-time right manufacturing operations and then subsequently move the product through the supply chain efficiently to the customers. It is also important that people understand the specific indication that the product is approved for and the area of therapy it serves.
Other workforce training areas include safety, health and environmental training, and OSHA training. We want to ensure that people are performing their jobs in a safe environment, and that they are always going to operate where they are free from potential injury or any physical stress that is created from the environment that they work in. Other items for the workforce would be Drug Enforcement Administration (DEA) for controlled substance production, materials management and inventory control. There are a whole variety of different procedures and restrictions in doing business with controlled substance products. So that is critical for any company that manufactures controlled substance products to carefully train their teams on the management of these processes. In addition, it’s particularly important that warehouse and logistics teams can warehouse and transport products utilizing proper warehousing procedures and Good Distribution Practices (GDP) to fulfill their responsibilities in the supply chain operation.
CDR: What are some of the challenges in maintaining/improving facilities and processes?
COLICCHIO: One key challenge in maintaining/improving production facilities and processes would include allocating the necessary level of capital expenditure (CapEx) investment for new or upgraded facilities and new production/process/analytical/utility equipment. This is a critical requirement that needs to consider the perspective of short-term and long-term benefits in addition to the return on investment. The investment should support the current operation along with meeting the strategic growth plans over the long term. Investments would also include maintaining the upkeep of the facilities and production areas. These CapEx investments need to be targeted to ensure that cGMP compliance requirements are always being met; productivity goals are achieved; and the production site is operating towards a sustainable basis with the growth framework in place. The prioritization of resources is needed to ensure that the facilities are operating in a compliant manner and that any new or improved production processes are fully developed and implemented in a robust manner. These investments will ideally help the site remain “audit ready” at all times for inspections by the Food and Drug Administration or any other regulatory body which will could also include the DEA, OSHA, environmental agencies, etc. that arrive on the site.
Some of the challenges also include recruiting and retaining facilities engineers and maintenance staff that are able to maintain the facilities, utilities, production equipment and the grounds. The utilities would include everything from power, compressed air, steam, HVAC, and related items. The production equipment would pertain to any aspect of manufacturing and packaging and overall production capabilities. So, it is important that you have a strong workforce that is well trained and can maintain the care of the facility for the current state as well as to position it for future growth.
CDR: How important are internal communications to process changes?
COLICCHIO: Process changes would require collaboration between R&D, technical services, production, engineering, quality assurance, regulatory affairs, operations, safety, etc. to review and implement any changes to the process and production equipment or the introduction of new pharma manufacturing technologies. The key concern is making effective changes to the production process to ensure a tangible benefit to business. These changes can result in benefits such as improving economies of scale; increasing batch yields; increasing overall product output; reducing operational cost; automating process equipment; introducing novel process technologies; and improving quality while always maintaining product supply.
While any facility or process changes are made, pharma companies need to always deliver their drug product supplies on time and in full to their customers to optimize patient access.
CDR: With the need for making drugs that are experiencing drug shortages, what, from your perspective, are the important aspects in manufacturing to producing these so they do not experience shortages?
COLICCHIO: One key area of the supply chain to minimize drug shortages is to procure a higher volume of raw materials and packaging components to ensure that you always have sufficient safety stock to produce the required finished dosage from drug product inventory. The recommendation — especially after applying the lessons learned from operating during the pandemic — is to procure three to four months of supply for active pharmaceutical ingredients (APIs), critical excipients, and other key raw materials and packaging materials that carry long lead times. It is also important for the API manufacturers to have sufficient supplies of key starting materials (KSMs) to produce APIs on time for your supply. In addition, pharma companies will look toward producing sufficient finished dosage form products with two to four months of inventory on hand at their warehouse or 3PL. With key products, that inventory level may increase to three to four months on hand. And that’s notable because while other companies may be experiencing drug shortages, with a sufficient finished goods inventory, you will be able to not only serve your core business needs, but also can fulfill the demand of any select product that is experiencing a drug shortage.
Pharma manufacturers also need to maintain sufficient production capacity to produce the required inventory of finished dosage drug products. Production equipment must be maintained and be ready for continuous operation. The Quality Control unit will need to also ensure the on-site and contract laboratories (if utilized) will have sufficient analytical equipment and capacity to meet the increased level of production output from the site. The Quality Control unit needs the proper number of analysts and materials available at all times.
In addition, the recommendation is for regulatory affairs to continue to track drug product shortages on the FDA website and to be in continuous communication with their FDA contacts to evaluate if there are any product shortages coming up on the horizon. Based on the FDA request, timely notification from regulatory affairs to the supply chain management unit is then required to determine which products need to be shipped to the market.
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