There are many steps that pharmaceutical manufacturers must take to grow their lab scale operations to commercial drug production – but there is plenty of room for error along the way. Failure to scale up operations with suitable technologies or efficient processes can result in unnecessary expense and waste. However, pharmaceutical manufacturers are increasingly implementing statistical methods to streamline the pharmaceutical manufacturing process. Advances in materials, measurement and modeling tools are increasingly enabling engineers to design and scale-up operations with greater efficiency.
Apply the scientific method
The scientific method may be familiar from early training in the life sciences, but it applies to even the most complex experiments and can even be mirrored in engineering practices in the development of a pharmaceutical production operation.
A good engineering model should reflect the scientific method. First, engineers must craft an objective statement (Define your objective) and then conduct an engineering review of technology options (Gather the relevant information). Next, they must build a preliminary model of the operation (Form a hypothesis) of which they evaluate for product safety and efficiency among other criteria (Test the hypothesis experimentally). The operation must then be optimized based on key learnings during the process development stage (Refine and repeat) until it is deemed ready for operation in the process model confirmation phase (Confirm).
Know your ratios
A successful scale-up requires a process suited to the product. Pharmaceutical manufacturers must carefully consider the method of product administration and dosage form. In the research and early development stages, products are made in very small batches that can support formulation and package development functions. During the process development and optimization stage, “pilot” batches should represent at least 10 percent of the production-scale batch to support preclinical and mid- to late-stage evaluations and stability studies.
Consider single-use solutions
Once used to support upstream operations, single-use technologies have been increasingly adopted by pharmaceutical manufacturers for use in downstream processes. Valued for their offering of increased flexibility and reduced costs at all life cycle stages, these disposable elements enable faster turnaround by minimizing the cleaning processes – which also require validation – and simplifying the process for changeover.
Several technical advances continue to fuel more widespread adoption of single-use systems in drug production, including material improvements and increased construction quality. The evolving regulatory environment and increasing need to be flexible and agile in a highly competitive market also plays a significant part in driving the demand for single-use solutions.
Find the right suppliers
To streamline the process of scaling up, pharmaceutical manufacturers should work with suppliers that can provide the validated materials and tools required in the quantities they need from initial development through production. Consistency prevents potential product safety issues as well as costly back-tracking to validation. Pharma EXPO 2014 (McCormick Place, Chicago; Nov. 2–5) — co-produced by PMMI, The Association for Packaging and Processing Technologies and the International Society for Pharmaceutical Engineering (ISPE) — will connect manufacturers with suppliers technologies and offer attendees a world-class educational conference program.
For more information or to register for the show, visit pharmaexpo.com.
PMMI, The Association for Packaging and Processing Technologies, is a trade association representing over 650 packaging and processing supply chain companies that provide a full range of packaging and processing machinery, materials, components and containers. PMMI actively brings buyers and sellers together through programs and events such as The PACK EXPO family of trade shows, packexpo.com, PMT Magazine, PACK EXPO Show Daily, networking events and educational programs.
PMMI organizes the PACK EXPO trade shows: PACK EXPO International, Pharma EXPO, co-located with PACK EXPO International and presented jointly with the International Society for Pharmaceutical Engineering (ISPE); PACK EXPO Las Vegas, PACK EXPO East, EXPO PACK México and EXPO PACK Guadalajara, connecting participants in the packaging and processing supply chain with their customers around the world. Coming Up: PACK EXPO International 2014, Nov. 2–5 (McCormick Place, Chicago); Pharma EXPO, co-located with PACK EXPO International 2014; PACK EXPO East, debuting Feb. 16–18, 2015 (Pennsylvania Convention Center, Philadelphia); EXPO PACK Guadalajara 2015, March 10–12, 2015 (Guadalajara, Jalisco, Mexico); EXPO PACK México 2015, June 16–19 (Mexico City, Mexico).
Learn more about PMMI and the PACK EXPO trade shows at PMMI.org and Packexpo.com.
ISPE, the International Society for Pharmaceutical Engineering, is the world’s largest not-for-profit association serving its Members through leading scientific, technical and regulatory advancement throughout the entire pharmaceutical lifecycle. The 20,000 Members of ISPE are building solutions in the development and manufacture of safe and effective pharmaceutical and biologic medicines and medical delivery devices in more than 90 countries around the world. Founded in 1980, ISPE has its worldwide headquarters in Tampa, Florida, USA and offices in Frankfurt, Germany and Shanghai, China and is publisher of Pharmaceutical Engineering Magazine. Visit www.ISPE.org for more information.