# Presentation: 098157

## Implementing New
Process Analytic Technologies:

The underlying challenges

PAT Subcommittee, June 12-13, 2002

**Process Analytic Technologies:**
**The underlying challenges**
**PAT Subcommittee, June 12-13, 2002**

**Justin O. Neway, Ph.D.**
**Executive Vice President, Chief Science Officer**
**Aegis Analytical Corporation**
**http://www.aegiscorp.com**

## Outline

**Background & information sources**
**Perceived benefits of PAT implementation**
**What are the underlying challenges?**
**What can manufacturers do?**
**What can vendors do?**
**What can the FDA do?**

## Background & Information Sources

**~15 Yrs in Process Development & Mfg.**
**Trained in Biochemistry & Microbiology**
**Worked in three Biotech/Pharma companies**
**Intimate with data problems in PD and manufacturing**
**~5 Yrs with Aegis Analytical Corporation**
**Venture funded by GlaxoSmithKline, Merck, Aventis**
**Invited presentations to ~30 top Pharma & Biotech**
**Customer advisory panel & requirements consortia**

## Benefits of PAT Implementation

**Greater control of product uniformity**
**Improved safety, quality compliance**
**Shorter cycle times, batch release times**
**Cost savings, supply chain stability**
**Moves us towards parametric release**
**Cost savings, lower inventory**
**Moves us towards continuous operations**
**Improved control, significant capital adjustment**
**What about today’s failure rates, compliance & yield problems?**

## The Quality Compliance Challenge

**US Drug products are of high quality BUT:**
**Increasing trend towards manufacturing problems**
**Recalls, disruption of operations, drug shortages**
**Negative impact on New Drug Applications (NDA)**
**Low efficiency manufacturing and QA**
**Slow innovation and modernization**
**Why do these problems occur?**
**Janet Woodcock, M.D.**
**FDA Science Board Presentation**
**November 16. 2001**

## Data-intensive Decision-making

**Identify and control Critical Process Parameters**
**Quality & regulatory compliance (GMP):**
**Parameter review for batch release**
**Setting defensible specifications**
**Investigation of atypical batches**
**Manufacturing process validation**
**Production trend analysis**
**Annual Product Reviews (APRs)**
**Process control (stability):**
**Shorten process start-up/scale-up times**
**Shorten trouble-shooting time/adverse trend reversal**
**Improve process stability, productivity & quality**
**Improve Return on Net Assets (RONA)**

## The Real Manufacturing Data Environment

**The necessary data are in many separate locations **

**LIMS**

**SCADA**
**DCS**
**PLCs**

**Batch**
**Records**

**ERP**

**Process yield & quality:**
***discrete & replicate data***

**Process instrument measurements:**
***discrete & continuous data***

**Operators, times, volumes, quantities:**
***discrete & replicate data***

**Material vendors, receive & release dates, equipment:**
***discrete & replicate data***

**PAT**
**Instruments**

**Warehouse**

## Decision-making “Inefficiencies”

**Several weeks of manual data retrieval**
**Not a priority for corporate IT, multiple data sources**
**Spreadsheet madness**
**“****Excel add-ins”, discrete, continuous & replicate data**
**Bewildering choice of inadequate software**
**Too many packages with too little real usability**
**Programming required from non-programmers**
**Antiquated ways to communicate results**
**Tables of highlighted numbers**
**Traditional 2D plots**

## The World Around Us

**Industry trends:**
**New instrumentation**
**Cheap data storage**
**Cheap computing power**
**Increased enforcement of GMP**
**Patent expirations**
**Industry consolidation, globalization**
**The technology already exists to adequately deal with the “inefficiencies”**

## PAT Data Analysis Technology Example

## Batch Release Technology Example - VPS

- Dryer
- Parameter

- API Parameter

- Dissolution Rate

- Coating
- Parameter

- Mixer
- Parameter

## The Advantages of PAT

**A Good Balance - Compliance and Economics**
**FDA:**
**Wants better compliance to ensure safety and efficacy**
**Wants better manufacturing efficiency to lower drug prices**
**Industry:**
**Wants to comply but lacks necessary software capabilities**
**Has been building the cost of failed batches into pricing**
**Wants to shorten cycle times to improve economics**
**For this to work, the realties of the manufacturing data environment must also be dealt with**

## What can we do?

**Industry: **
**Boost **_**manufacturing IT**_** spending**
**Include mfg. users in budget prioritization**
**Implement underlying IT infrastructure needed for PAT**
**Vendors:**
**Make better software systems, work with industry**
**Be honest about software capabilities**
**Provide better training & support**
**FDA:**
**Continue emphasis on GMP compliance, outreach**
**Take opportunities to emphasize positive PAT economics**

## What can we do?

**PAT subcommittee:**
**Continue “safe harbor” policy implementation**
**Account for additional necessary mfg. infrastructure**
**Publicize compelling economic justification**
- Account for hard costs, soft costs and social costs
**Sponsor industry/vendor working groups**
- Define needs, develop requirements, provide feedback

## Conclusions & Recommendations

**PAT implementation, more difficult than expected**
**Requires much more than just new instrumentation**
**Challenges similar to other data-intensive decision-making “inefficiencies”**
**Poor data availability, inappropriate software systems**
**PAT – a unique economic incentive for quality compliance improvement **
**A good balance between compliance and improved economics**
**FDA - a catalyst for vendors, industry to work together**
**Gather data to show real world manufacturing software needs**
**Publicize the positive economics of PAT & quality compliance**
**Provide forums for industry/vendor collaboration**