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Best practices help mitigate generic drug shortages.
Drug shortages have been an ongoing challenge that FDA and pharmaceutical manufacturers have been struggling to mitigate. The COVID-19 pandemic exacerbated the problem, with shutdowns and global trade disruptions combined with sudden demand for critical drug products. FDA’s report on drug shortages for calendar year 2020, however, says that the US government and manufacturers worked together to prevent 199 shortages (1). The Agency said that the requirements for early notification helped reduce problems (1).
Supply challenges in 2020 were global in nature, says Vincent Colicchio, vice-president, Supply Chain and External Manufacturing, at generic drug supplier Dr. Reddy's Laboratories. Consistent supply of APIs and some of the key starting materials for manufacturing APIs were particularly challenging for many pharma companies during the pandemic, he notes. Having adequate staffing for manufacturing operations, laboratories, and facility maintenance has been a challenge as well. Pharmaceutical Technology spoke with Colicchio about best practices regarding supply chain and workforce training and retention.
PharmTech: From your perspective, what are the important aspects to preventing drug shortages?
Colicchio (Reddy’s): One key priority of the supply chain is to minimize drug shortages by procuring a higher volume of raw materials and packaging components to ensure that you always have sufficient safety stock to produce the required finished dosage form inventory. The recommendation—especially after applying the lessons learned from operating during the pandemic—is to procure three to four months of supply for 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 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 [third-party logistics provider]. With key products, that inventory level may increase to three to four months on hand. And that is 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 strive towards fulfilling the incremental 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 (QC) unit needs to also ensure that 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 QC unit requires the proper number of analysts and materials available at all times.
In addition, the regulatory affairs group needs 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.
PharmTech: Do you see any concerns in the pharmaceutical industry for having enough trained employees, in the QC lab or elsewhere? What are some best practices in ensuring that existing or new employees have the skills they need?
Colicchio (Reddy’s): Having enough trained QC personnel was a challenge even before the pandemic. It’s essential to ensure that the QC units are staffed with a sufficient workforce to test the normal production demand as well as being able to take on spikes in demand. In addition, there is a current shortage of skilled production operators. Pharma companies need to train operators to be proficient on the shop floor with the latest equipment and technologies. Traditional oral solid-dosage drug manufacturing requires conventional skill sets, but sterile injectable, transdermal, and inhalation drugs are more difficult to manufacture drug products due to the more complex production technologies. These types of products are produced with complicated equipment and require different kinds of skill sets.
Other challenges include recruiting and retaining capable facilities engineers and maintenance staff that are able to maintain the facilities, utilities, production equipment, and the grounds. There is a significant amount of competition for engineers and maintenance staff. The competition comes from other pharma companies as well as the growth of e-commerce businesses and the establishment of fulfillment centers.
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. Workforce training is a dynamic requirement that impacts several groups to support or perform generic drug manufacturing, including manufacturing operations as well as cross-functional groups that play key roles, including packaging, engineering, technical services, maintenance, metrology, facilities, quality assurance, quality control, warehouse, distribution, etc.
Training in current good manufacturing practices (CGMP) is fundamental for all pharma manufacturing, including generic drug manufacturing. Other key training elements are in good documentation practices and in adherence to standard operating procedures (SOPs). Steadfast adherence to the SOPs and batch records will ensure consistency in execution of the manufacturing processes to ensure the patient’s safety and avoid product recalls in the market. Other workforce training areas include safety, health, and environmental 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 would be training in Drug Enforcement Administration (DEA) [protocols] for controlled substance production, materials management, and inventory control. There are specific procedures and restrictions in doing business with controlled substance products. In addition, it is particularly important that warehouse and logistics teams can warehouse and transport products utilizing proper warehousing procedures and good distribution practices to fulfill their responsibilities in the supply chain operation.
PharmTech: What do you see as challenges in maintaining and improving facilities?
Colicchio (Reddy’s): One key challenge in maintaining and improving production facilities and processes is allocating the necessary level of capital expenditure investment for new or upgraded facilities and new production/process/analytical/utility equipment. A critical requirement is 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 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. In addition, these investments should ideally help the site remain ‘audit-ready’ at all times.
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.
PharmTech: Do you see tangible benefits for digitalization in generic drug manufacturing?
Colicchio (Reddy’s): Yes, we have invested in digitalization for the overall business, particularly for integrated business planning systems. We aim to integrate supply data with business and operations systems to have ‘one version of the truth’ in place for demand forecasting and supply planning. From there we can digitize sales and operations planning, which offers benefits for long-term planning and capacity planning. Integrated digital systems are powerful in all aspects of supply and finance, and they can drive manufacturing activities, which can help prevent drug shortages. Ideally, we can identify potential supply gaps and plan to improve product supply to meet the needs of our customers and improve patient access for our products. Data analytics systems can also help improve process efficiency and operational agility.
1. FDA, Drug Shortages for Calendar Year 2020, www.fda.gov/drugs/drug-safety-and-availability/drug-shortages.
Jennifer Markarian is manufacturing editor at Pharmaceutical Technology.
Vol. 45, No. 11
When referring to this article, please cite it as J. Markarian, “Meeting Supply and Training Challenges,”Pharmaceutical Technology 45 (11) 2021.