Guest Blogger

	Guest blog written by Walter Morris, Director of Publishing, Parenteral Drug Association, on behalf of the PDA Quality Metrics Task Force

	The US FDA Center for Drug Evaluation and Research (CDER) reached out earlier this year to industry and the public for input into plans to implement parts of the 2012 Food Drug Administration Safety and Innovation Act (FDASIA).

 Quality manufacturing leaders in the industry must now seize this opportunity to help bring about real changes to a system of regulatory inspection and enforcement that, in spite of reasonable attempts at reform over the last decade, is struggling with new challenges. Continued high-cost enforcement actions, plant closures, drug shortages and, regrettably, real harm to patients have pushed everyone involved with this industry to recognize, finally, that a new regulatory and quality paradigm is needed.

	FDASIA is the potential game-changer. Section 705 of the Act requires FDA to implement a risk-based inspection regime. FDA has been moving in that direction anyway, but with it now codified, the agency must reorient its inspection program to comply with the law. Section 706 of the Act allows FDA to request, and firms to provide, records in advance of or in lieu of inspections.

	Neither 705 nor 706 provide any kind of detail on implementation, and FDA is reaching out to industry to help fill in the details before they issue formal guidance.  CDER officials are exploring Quality Metrics as records they would request and needs help defining what Quality Metrics should be used as inputs into an Inspectional Risk Model, which helps determine inspection frequency.

	PDA supports this endeavor and has launched an initiative to draft a “Points to Consider” (PtC) report to share with FDA. The PtC will express PDA’s general support for the use of Quality Metrics in the FDA Inspectional Risk Model, with some caveats. There exists no single set of metrics that can act as a surrogate to reliably predict quality or compliance across different sites, products, and companies. Secondly, use of Quality Metrics will create even more challenges for industry.

	PDA, however, recognizes the many benefits of metrics. These include potentially enhancing visibility/transparency between industry and regulatory, prioritizing and focusing on the most important issues, elevating (finally) an organization’s focus on quality and driving continuous improvement.

	For these reasons, PDA’s “Points to Consider” paper on Quality Metrics will discuss the importance of both manufacturing quality performance metrics that can be used in FDA’s Inspectional Risk Model, and continuous improvement metrics that industry should embrace to ensure continuous improvement of quality internally.

	Both types of metrics present challenges to define. Manufacturing quality performance metrics will be grounded in GMPs, with few shared definitions across the industry. Still, PDA believes that many commonalities can be fleshed out as objective metrics. For instance, the PDA task force has already identified several groupings of common metrics with respect to manufacturing quality performance for products and sites. These should be quantitative and focus on GMP requirements that would be discussed during a GMP inspection.

	Continuous Improvement Metrics, on the other hand, might offer the best path forward to real improvements in manufacturing quality, but they will be more subjective and much harder to define and measure across the industry.

	To help PDA provide the FDA with a meaningful and impactful PtC report, the Association is inviting industry leaders and regulators to participate in its upcoming 

Pharmaceutical Quality Metrics Conference,

 December 9–10, which will be co-chaired by FDA officials and include strong participation from FDA personnel. Discussion of Product Quality Metrics, Site Quality Metrics, Continuous Improvement Metrics, and Comparing Metric Outcomes will occur in four interactive sessions.

	References
	1. Department of Health and Human Services, Food and Drug Administration. Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments; 

Articles

Guest blog written by Walter Morris, Director of Publishing, Parenteral Drug Association, on behalf of the PDA Quality Metrics Task Force.

Industry Needs to Drive the Dialogue Regarding FDA’s Quality Metrics Initiative

	More than a year has passed since the FDA issued its guidance, “

Process Validation: General  Principles and Practices

,” which describes process validation in three stages – Process Design, Process Qualification and Continued Process Verification. Companies are making progress with how to incorporate these guidelines cost effectively for science-based decision making that improves quality–the consequences of poor quality are too costly.

	The guideline for Stage 3 – Continued Process Verification – states, “An ongoing program to collect and analyze product and process data that relate to product quality must be established (§ 211.180(e))…The data should be statistically trended and reviewed by trained personnel. The information collected should verify that the quality attributes are being appropriately controlled throughout the process.”

	In reality, manufacturers have to balance available resources (i.e., “trained personnel”) with tasks such as accessing and aggregating data from multiple sources, including paper records. This can be especially challenging without proper IT systems in place to effectively manage process validation data throughout the tech transfer and manufacturing process.  When evaluating technology options, manufacturing teams should look for tools that can help them more easily monitor product and process data as outlined by the FDA.

	Companies that adopt QbD and implement best practices for data analysis to achieve a culture of process understanding will reap greater rewards, including:

		Lower final product testing and release costs and reduced operating costs from fewer deviations and investigations

		Reduced raw material and finished product inventory costs

		Faster tech transfer and regulatory approval of new products and process changes

		Fewer and shorter regulatory inspections of manufacturing sites.

More than a year has passed since the FDA issued its guidance, “Process Validation: General Principles and Practices,”.

Putting FDA’s “Process Validation” Guidance into Action

	Gartner has developed a body of research around the convergence of IT and Operational Technology (OT) and the implications for organizations (1). Much of the research speaks to the opportunities and challenges this convergence presents to organizations. By way of definition operational technology, according to Gartner, refers to “physical-equipment-oriented technology” (e.g., manufacturing equipment) that is shifting from proprietary, hardware-based to open, software-based technology. Thus the lines are becoming blurred as to who “owns” and supports the infrastructure, integration, upgrades, security and analyses of OT software systems.

 Gartner contends that companies which align IT-OT strategies and tactics stand to gain cost savings, better decision making, better business and process intelligence, and more efficient project and resource management. The analyst firm identifies the challenges of integrating and supporting people, processes and technologies across organizations.

Why CIOs Are Aligning Operational Technology and IT

,” says: “Kristian Steenstrup, research vice president and Gartner fellow, says IT leaders should be interested in the IT-OT alignment question. ‘There’s only so many incremental improvements you’re going to get in the IT systems to improve the systems performance … You can get transformational change in the organization by combining the IT-OT alignments.’”

	Most organizations are just beginning to see the business benefits of aligning the planning, processes and support between IT and OT to avoid islands of technology. The CIO and IT organization need to adopt a leadership and consultative role to the business operations groups while allowing operational areas to implement and customize the software and applications that best meets business users’ needs.

	The pharma industry is faced with downward price pressures, drug shortages, and manufacturing and quality challenges. To address these obstacles, companies need to collaborate across business groups, IT and throughout the supply chain to optimize information sharing across systems that enable better business decision making. There are several examples of pharma companies bridging IT and OT for greater manufacturing process intelligence through a common data sharing platform.

	Current IT systems such as transactional systems (LIMS, MES, CAPA, etc.) and traditional data warehouses support the data reporting and analysis needs of many key areas within an organization including finance, sales and marketing.  Current specialized OT software provides views of what is happening (and has happened) with devices on the factory floor.   Manufacturing Intelligence (MI) systems either focus on the IT systems, or provide rudimentary capabilities for tying together IT- and OT- produced data, and focus on high-level views of “what happened” via dashboards and portals.

	What are emerging are Process Intelligence solutions that provide user-centric access (e.g., Manufacturing, Quality, Tech Transfer) to the different types of data found in traditional IT and OT systems – including discrete, replicate, event-based and continuous – for powerful process understanding across geographically dispersed manufacturing networks. In essence, these systems provide powerful, easy-to-use functionality to go beyond MI’s “what happened?” to answer the question “why did it happen?”   For example, a pharma manufacturer can leverage data from multiple systems while leveraging existing IT and OT investments for faster incident resolution, reduced time spent on regulatory reporting, and site-to-site comparisons for best practices at multiple sites. Greater process understanding increases predictability and decreases variability.

	For the enterprise, this type of bridge across the existing IT and OT boundaries requires less infrastructure, fewer staff and resources and provides more flexibility and responsiveness to business end users.  These benefits stack up nicely with the other cost and efficiency-related business results Gartner mentions – and justifies investment in OT-IT alignment.

	1.     Kristian Steenstrup, “IT and Operational Technology: Convergence, Alignment and Integration,” Gartner, Feb. 15, 2011.

This blog post was written by Joe Rothman, Chief Technology Officer, Aegis Analytical. 

Gartner has developed a body of research around the convergence of IT and Operational Technology (OT) and the implications for organizations (1).