To fast-track the time to market and gain a competitive edge, pharmaceutical development companies are increasingly implementing single-use technologies (SUT).  Single-use technologies are built using an array of components, including sampling bottles, tubing, filters, clamps, check valves, sterile connectors, Luer locks and fittings, seals and gaskets, and dispensing tips/nozzles. The technology can be as simple as a single assembly, or an entire system made up of multiple complex assemblies that are utilized across the entire manufacturing process including formulation, upstream/downstream processing, and final product filling.
 
SUT offers many benefits compared to traditional stainless-steel systems such as the elimination of clean-in-place or steam-in-place (CIP/SIP) requirements, faster changeovers between batches resulting in reduced production time, more flexible infrastructure, and a decreased risk of cross-contamination.  
 
Although standard, off-the-shelf SUT assemblies are currently available, most are narrowly focused on upstream processes using kit components like bottles, tubing, connectors, and filters likely supporting research applications. There are, however, a few companies leading the innovation of single-use systems for fill/finish.  In addition, novel biologics and synthetic compounds often have unique manufacturing processes that require custom assemblies that are more advanced than standard off-the-shelf options.
 
Given the increasing adoption of single-use technology for both small and large molecule drug development, one area of emphasis to speed time to market is outsourcing the design, development, production, and validation of the SUT assemblies and systems.  
 
Invest Upfront and Focus on the Science
By outsourcing, companies can keep the scientists and engineers focused solely on new product development.  As product development progresses, scientists should not be spending their time designing and putting together bottles, caps, and tubing system, but instead maintain focus on the product.  Unfortunately, off-the-shelf components may not meet the requirement.
 
Single-use systems comprised of various components can quickly become a complex system that requires expertise in choice of materials, biocompatibility, connection strength and integrity.
 
“Research into the development of single-use systems can be a major distraction to the product development process.  With a qualified supplier that can integrate phase appropriate manufacturing solutions, companies can focus on the science and new product development,” said Meghan Elizabeth, Manufacturing Operations Manager at Intellitech, Inc., a manufacturer of single-use process components and assemblies, cell transfer bottles and manifolds for the pharmaceutical, life sciences and specialty chemical industries.
 
Develop SUT in Parallel with Drug Product
As a product moves out of R&D into clinical trials and then into commercial manufacturing the requirements become more stringent and the SUT development should build concurrently. This type of approach focuses on specific requirements at each phase rather than a one-size-fits-all approach.
 
“Phase appropriate implementation of SUT into the manufacturing process can be integral to accelerating the speed to market,” said Elizabeth.  “When small batches of product are being manufactured at the bench, the focus is on consistency and repeatability to increase the likelihood of successful scale-up.”
 
As a product progresses from the bench into clinical trials, the next phase of SUT development is to conduct validation studies and provide documentation that can support the customer’s Investigational New Drug (IND) Application and Good Manufacturing Practices (GMP) required by the FDA.  GMPs assure proper design, monitoring, and control of manufacturing processes and facilities.  This includes establishing quality management systems, obtaining appropriate quality raw materials, detecting product quality deviations, and collaborating with third party, accredited testing laboratories for method feasibility and validation studies.
 
“Instead of investing the time required for the design and management of validation studies, a company can partner with a SUT supplier that can aid in risk-based solutions and manage the project directly with the lab,” said Elizabeth, adding that because SUT assemblies are typically custom designs with unique components, the validation process is considerably more complex than in the past.
 
As a result of this complexity, many pharmaceutical and specialty chemical developers and manufacturers are finding their unique requirements better served by outsourcing to a qualified and experienced SUT supplier that can provide phase-appropriate solutions along with the necessary validation and documentation to navigate each product development phase from R&D through to commercial manufacturing.
 
Partner with an Experienced SUT Design Firm
To facilitate the transition from R&D to commercial manufacturing and increase speed to market, an experienced SUT supplier has:
–       An established supply chain of research and GMP compliant components
–       A design library of proven, leak proof connection
–       Validated manufacturing, assembly, testing and packaging processes, and a registered quality management system
 
Additionally, if a component is not commercially available, the supplier can design and print 3D parts that are compliant with the customer quality and regulatory requirements such as biocompatibility and non-animal origin.
 
“A knowledgeable supplier tailors the SUT design and development to align and grow with the customer’s product development based on phase appropriate requirements, manufacturing strategy and risk-assessment,” explains Elizabeth.

BPI Labs, LLC, a subsidiary of Belcher Pharmaceuticals, is a current Intellitech customer that focuses onthe development and manufacturing ofinjectable medicines. According to Brian Neuman, a Principal Engineer at BPI Labs, the company has approximately 50 injectables in various phases from early R&D to commercial manufacturing and packaging. With so many products in development, single-use technology is particularly suited to their operation.
 
“There are companies that just manufacture a product nonstop and never have to make a change,” said Neuman.  “But that is not the goal of our company.  We are always trying to expand what we produce here, and that just inherently means we will have different requirements along the way.”
 
Given their unique and constantly changing requirements, BPI Labs decided to outsource the non-proprietary SUT assemblies and systems to an experienced company that could provide more flexibility.
 
“We were able to have meetings with them to bring up all the specific requirements we have for our facility and our process,” said Neuman.

According to Elizabeth, Intellitech works with customers to validate processes and define acceptable operating ranges, critical quality attributes, and acceptance criteria of the intended system.  The company also partners with accredited labs for testing seal strength, integrity, bioburden, sterility, and shelf life.

The company also creates, approves, releases, and maintains the required documentation to support GMP requirements.  This includes drawings, bill of materials, work instructions, data collection forms, batch records, and Certificate of Conformance.