The Quality by Design Initiative

By: Gary Miller, CIS Senior Compliance Associate
garymiller@cis-partners.com

In 2005, the Food and Drug Administration (FDA) started a pilot program to allow participating companies to submit chemistry manufacturing and controls (CMC) information demonstrating the application of Quality by Design (QbD). The drug applications to be reviewed during this pilot program are meant to provide examples of how design, space and process knowledge can be captured at an operational level, and how they can relate to normal operating ranges, equipment, and scale. [1] QbD is fundamentally built upon the theory of continuous process, which has been used in chemical manufacturing for quite some time now.

The Center for Drug Evaluation and Research (CDER) Office of New Drug Quality Assessment has stated that “the pharmaceutical industry can only realize the full benefit of QbD by developing and implementing continuous process.”[2] The FDA has a view of QbD as a “systematic approach to product and process design and development.”[3] Lawrence Yu, PhD, director for Science Office of Generic Drugs for the FDA, defines QbD as “designing and developing formulations and manufacturing processes to ensure predefined product quality. This involves the understanding of controlling formulation and manufacturing process variables affecting the quality of a drug.”[4]

In an attempt to reach this necessary understanding, the FDA has granted the National Institute of Pharmaceutical Technology and Education a $1.19 million contract. The FDA has said that “The intention of this award is the development of specifications allowing for the implementation of Quality by Design (QbD) framework to improve product quality through science and technology.”[4] The ultimate goal of this research, along with all principles of QbD, is to improve end product quality. The research is scheduled to end in September of 2010, and “the results of the study will potentially serve as the basis for formulating best practices and developing science based guidance documents that can be used by the FDA to evaluate new and generic drug applications.”[4]

Some of the key elements of QbD have already been identified. Chi-wan Chen, Deputy Director of the Office of New Drug Quality Assessment at the CDER, outlined some of the features of QbD that have already been identified in subsequent studies. The elements include:

• Targeting the product profile
• Determining the Critical Quality Attributes (CQAs)
• Linking raw material attributes and process parameters to CQAs and perform risk assessment
• Developing a design space
• Designing and implementing a control strategy
• Managing product life cycle, including continual improvements [3]

The movement towards a QbD manufacturing system is a challenging one, but it claims that it will be beneficial for business processes and that, ultimately, it will have a positive financial impact on healthcare. QbD can be heavily equated with the Just in Time (JIT) manufacturing methodology. With this, an immense amount of “waste” could potentially be eliminated, lowering costs in all areas of production and processing. Process controls can be applied that will produce consistent quality product, with minimal or no in-process testing. Similar methods and observations can be incorporated in the development of new chemicals so that a QbD process is developed from the outset. If QbD simplifies process development and manufacturing methods for APIs, the Pharma industry may be able to look at “first time quality” as a driving manufacturing force behind drug efficacy. [2]

So where does the implementation stand today? Big Pharma has been able to pursue this avenue with effectiveness, but many mid-tier Pharma companies have fallen back on old habits. It is believed in the industry that the FDA must continue to apply more pressure on the companies to change, or they will not see a need to expel the resources needed to make significant changes. Success also relies on the industry and the FDA moving toward a cohesive methodology, and sending a message explaining the need for these changes. Designing a QbD solution that is both pragmatic from a compliance standpoint, and flexible from a business perspective, will keep the pressure on industry to truly embrace the principles of QbD. [6]

Sources:
1. FDA Promotes QbD for Biotech Therapies - By Jill Wechsler, October 1, 2008
http://biopharminternational.findpharma.com/biopharm/Quality/FDA-Promotes-QbD-for-Biotech-Therapies/ArticleStandard/Article/detail/557244

2. “Quality by Design (QbD): Myth or Reality” - By Girish Malhotra, PE, President EPCOT International
http://www.pharmpro.com/ShowPR.aspx?PUBCODE=021&ACCT=0000100&ISSUE=0702&RELTYPE=PR&ORIGRELTYPE=ATO&PRODCODE=0000&PRODLETT=N&CommonCount=0

3. FDA Perspective on Quality by Design - By Patricia Van Arnum, Dec. 5 2007
http://pharmtech.findpharma.com/pharmtech/Article/A-FDA-Perspective-on-Quality-by-Design/ArticleStandard/Article/detail/469915

4. Implementation of Quality-by-Design: OGD Initiatives - By Lawrence Yu, PhD, Director for Science Office of Generic Drugs, FDA
http://www.fda.gov/ohrms/dockets/AC/06/slides/2006-4241s1_8.ppt

3. FDA Awards NIPTE $1.19 Million Contract to Develop Quality by Design (QbD) Guidance Elements - October 29, 2008
http://www.businesswire.com/portal/site/google/?ndmViewId=news_view&newsId=20081029005227&newsLang=en

6. QbD: An Interim Report Card - By Bikash Chatterjee, Pharmtech Associates, Inc.
http://www.pharmamanufacturing.com/articles/2007/158.html