August 22, 2018 PAO-08-18-CL-002
In pharmaceutical manufacturing, fill-finish operations are critical, since fill-finish is the last step before a product is packaged and ultimately delivered to the patient. By the time a drug reaches this stage, the drug product is highly valuable, as it has already been through labor- and cost-intensive production stages, including upstream processing, cell culture or fermentation and downstream purification. Failures in the integrity of the fill-finish stage can introduce microbial contamination and generate issues with formulation and dosing.1 The result could be loss of valuable product, production delays or even potential health risks to patients if the issues are not identified before the product reaches the market. Because of the potential risks to patients of contamination or drug product degradation that can be introduced at this critical manufacturing stage, as well as their highly technical nature, fill-finish operations are the subject of significant regulatory scrutiny.
As a result, fill-finish requires specialized capabilities and equipment, as well as close coordination and interaction among personnel, equipment and facilities. Aseptic fill-finish operations bear more potential risks than non-sterile processes and as such require yet greater specialization and analysis. Aseptic fill-finish must be performed in a sterile environment, and all equipment and components must themselves be regularly sterilized. Expert oversight is necessary to ensure that the correct method be chosen (e.g., steam, dry heat, fumigants, radiation) to achieve sterilization without impacting the stability or pharmacokinetic properties of the drug product.2 Products that require lyophilization demand further sterile procedures to prevent the introduction of microcontamination during loading and unloading of the sterile dryer.
Additionally, lyophilization, or freeze drying, is often required in the production of stable formulations of sensitive parenteral drugs, particularly biologics. Creating appropriate aseptic conditions for lyophilization is an additional technical challenge for manufacturers, involving complex heat and mass transfer processes. Business consulting firm Roots Analysis predicts that the lyophilization market will grow at 9.5% annually from 2017 to 2027.3 In order to achieve lyophilization, both specialized equipment and expertise are required.
Owing to the technical challenges and corresponding specialized expertise associated with aseptic fill-finish operations, pharmaceutical and biopharmaceutical companies are increasingly relying on contract development and manufacturing operations (CDMOs) to manage this crucial phase of production. Many companies do not possess adequate fill-finish operations for sterile products, but even companies with these capabilities use CDMOs as a backup source or switch from in-house operations at early development stages to an outsourcing partner for commercial manufacturing. In the 2017 Nice Insight CDMO survey of over 700 pharmaceutical industry professionals, the top reason given for engagement with CDMOs was “access to specialized technologies,” and 54% of respondents reported engaging outsourcing providers for clinical- and commercial-scale liquid dose form manufacturing services.4
Sterile fill-finish service providers are clearly responding to the increased demand for capacity and technical expertise, which in many cases exceeds available capacity. In the 12th Annual Report and Survey of Biopharmaceutical Manufacturing conducted by BioPlan Associates, eight out of ten respondents reported that they were planning to add at least one new technology to their fill-finish operations within the next two years. The majority of these respondents were employed by CDMOs.5
Innovations in digitization, integrated IT, automation and environmental conditioning systems are driving this dynamic outsourcing segment. The broader shift in the pharmaceutical market from blockbuster drugs to specialized, targeted therapies intended for small patient populations is creating a need for fill-finish operations with flexible capabilities. These small-batch aseptic products not only create a new set of sterilization, handling and filling challenges, they require faster speeds to market.
The transition to flexible and multi-product fill-finish operations has been facilitated by advances in cleanroom technology, including isolators and restricted access barrier systems (RABS). Single-use technologies have been a driving force in fill-finish operation innovations, although it appears unlikely that single-use systems will ever entirely replace stainless steel equipment in these settings.6 Increased automation in fill-finish equipment and facilities is reducing many of the past sources of contamination risk. Wider industry trends, such as increased digitization, the push toward Industry 4.0 manufacturing models and serialization, are transforming both fill-finish operations themselves and the perception of the operations in broader development and manufacturing strategies. Fill-finish operations also need to remain flexible to keep up with changing, patient-centric demands for new drug-delivery systems that can better fit patient lifestyles and increase convenience and adherence.6
For pharmaceutical companies maintaining their own in-house fill-finish operations for early development, clinical trials or commercialization and CDMOs providing those services to their customers, it is essential to make the best decisions when procuring equipment. The diverse considerations related to sterile fill-finish manufacturing ––from maintaining the sterility of the cleanroom and the equipment itself to assuring that the finished product is free of contamination without any degradation to the drug product itself –– make it especially critical to install the best and most appropriate equipment and to understand the capabilities and specifications of any equipment purchases from the planning stages.
A strategic partnership with an equipment supplier like Federal Equipment Company –– with strong experience with a wide range of equipment manufacturers and with clients experienced in specialized services like sterile fill-finish –– is a crucial asset for any company looking to build or expand their fill-finish operations. Federal Equipment Company offers competitive prices on thousands of pieces of used pharmaceutical processing equipment from top equipment manufacturers. This includes aseptic fill-finish equipment, such as aseptic processing and filling machines, sterilizers and lyophilizers, for a range of packaging types (e.g. vials, ampoules, prefilled syringes), offering customers cost savings as well as reduced lead times for installation.
Federal Equipment Company offers additional relevant value-added services, such as operator training and equipment and bio-decontamination, to assist customers beyond just their equipment needs. Federal Equipment Company offers a validated three-step decontamination process that assures that equipment is free from β-lactam antibiotics and 99.9999% of potentially harmful pathogens and contaminates.
Justin Kadis works in marketing and business development for Federal Equipment Company, a major supplier of used manufacturing equipment for a wide variety of industries. He graduated from Boston University with a Bachelor of Science in Business Administration degree with a concentration in marketing.