Opportunities in pharmaceutical manufacture occur at interfaces. The interfaces are not physical borders of cells or product surfaces, but rather conceptual areas where ideas and/or technologies must be blended. Pharmaceutical manufacture has the advantage of having well-established standards and best practices.
Change can be gradual, and it is easy to assume that the cleaning and monitoring protocols that worked before will still be successful. Because cleaning protocols and monitoring protocols are well-established, cleaning may be viewed as a commoditized activity. In some companies, if a new product line is established, the selection of cleaning agent may be made based on a competition between product supplied by the top two or three vendors — all have been acceptable, and so all are considered equivalent. The final decision may be made solely on cost, because performance is expected to be equivalent for the old and new product. Sometimes, equivalence is not perfect– we hear many comments about unexpected residue in newer pharmaceutical formulations. Such residue may be detected because it forms a visible precipitate. Is it the active pharmaceutical ingredient (API), or a derivative of the API?
Dazzling new products are inherently scientifically interesting, potentially profitable, and disruptive. The leader of a recent workshop concerned with global QMS (Quality Management Systems) for combination devices1 explained that it is essential to understand the landscape of the quality systems. Wabby pointed out that manufacturers must consider the impact of both the pharmaceutical cGMP2 and the medical device QSR3. There may also be specific concerns related to other regulations. The challenge, if there are conflicts, is to determine and comply with the regulation that is pertinent to the specific part under consideration.
Stepping up to the plate
The final assembler is the responsible group. Unfortunately, this can lead to a cavalier attitude on the part of suppliers, especially in terms of cleaning and contamination control. For specialized pharmaceuticals and combination devices, assuring quality has to be a life-cycle issue. It has to start during R&D, to be cast in concrete prior to validation and to continue in the form of monitoring and audits4.
FDA and globalization
The FDA is addressing the issue of complex, global supply chains. The FDA regulates the final product; they do not “approve” materials used in the product. The FDA is taking steps to address the challenges of the global supply chain through the FDASIA (FDA Safety and Innovation Act). The act takes a risk-based approach and includes a registration system for both domestic and foreign manufacturers as well as enhanced inspection. While stepped up inspections are possible, the system is also data and document driven. The interfaces associated with new products, new business plans, and new requirements challenge our assumptions about critical cleaning and contamination control. Such challenges are crucial to maintaining state-of-the-
1. James Wabby, “The Importance of a Global Quality Management System: Drug Device Combination product case study and workshop,” MD&M, Anaheim, Calif., Feb. 11, 2015.
2. “Drug Applications and Current Good Manufacturing Practice (CGMP) Regulations,” http://1.usa.gov/1HfqVvS
3. “Quality System (QS) Regulation/Medical Device Good Manufacturing Practices,” http://www.fda.gov/medicaldevices/deviceregulationandguidance/postmarketrequirements/qualitysystemsregulations/ (accessed 3/16/2015).
4. B. Kanegsberg and E. Kanegsberg, “2020 Pharma,” Controlled Environments Magazine, March 2014
Barbara Kanegsberg and Ed Kanegsberg (the Cleaning Lady and the Rocket Scientist) are experienced consultants and educators in critical and precision cleaning, surface preparation, and contamination control. Their diverse projects include medical device manufacturing, microelectronics, optics, and aerospace. Contact: firstname.lastname@example.org
This article appeared in the April 2015 issue of Controlled Environments.