biovia-informatics-biopharma

To deliver safe, life-saving medicines and compete globally, life science companies are facing enormous challenges. Not only does the globalized Pharma industry mean more competition from players around the world, it also means fielding operations in strategically important regions to compete in local markets with similar local players. For example, today, 80 percent of APIs are manufactured in India and China.

Compliance pressure is steadily growing, and com-panies are challenged by increased scrutiny from the U.S. FDA and other regulatory agencies. According to one source, foreign inspections by the FDA are expected to increase 17 percent this year. To put that in perspective, compliance with global standards typically means 35 percent higher manufacturing and maintenance costs. Meanwhile, governments are putting pressure on the price. Margins are decreasing and governments have been successful at negotiating discounts of between 27 and 49 percent off the list price of drugs.

The patent cliff still presents a challenge for all the industry to bear and many patents have expired or are about to expire. Some $66 billion worth of sales were from drugs that had their patents expire in 2015. The average cost to develop a new drug ranges from $1.2 billion for smaller companies, up to $4 billion for larger companies and takes an average of 12 years.

Because it takes longer to discover, develop and market new drugs, productivity in R&D is declining and

the costs for developing new products are increasing exponentially. Generics have left their mark on Pharmas competitive landscape as well. More than 85 percent of prescriptions written today are for a generic form of some once patent-protected medicine, and while Generic Pharma has taken trillions out of the cost of drugs over the last three decades, competition in this sector is fierce with former patent holders and generic companies vying to capture lucrative portions of popular medications.

Industry observers also point out that Pharmas own shortcomings challenge itself to a great degree likely the result of its many years as a closed, insular sci-ence-driven industry, ignoring or diminishing the best practices associated with the other more streamlined and leaner manufacturing and processing environments. Many recognize that in contrast to other industries, pharmaceutical manufacturers are not very efficient at making drugs and continue to support high-variability practices from the laboratory to the shop floor. Fortu-nately, the industry is paying attention, with 50 percent of multinational companies implementing improvement initiatives like Lean Six Sigma programs to improve operational excellence and manufacturing efficiency. Bristol-Myer Squibb (BMS), for example, was able to reduce cycle times by 80 percent through its recent Lean Six Sigma initiative (see sidebar).

Most organizations in the industry share four common

Informatics Role in Biopharmaceutical Product & Process Development

WHITE PAPER Biopharmaceutical Informatics

BIOVIA INFORMATICS ROLE IN BIOPHARMACEUTICAL 1

Development Informatics

Discovery Informatics

Target Identification and Validation Predictive Analytics Cloning and

Expression Assay Development

Lead Identification Characterization and Optimization Safety

and PreclinicalManufacturing and Regulatory

Sequence Analysis Activity Analysis Developability

Calculations

Biophysical/ -chemical

Affinity Maturation Humanization Validated

Monoclonality

Cell Culture, Recovery/Purification Formulation/Delivery Process Development Stability

Scale-up Process Optimization

and Monitoring Product Optimization Regulatory

Compliance

Manufacturing Informatics

Information Management

Biologics Product Development Life CycleInformation Management Throughout the Product Life Cycle

Wednesday, July 15, 15

goals: improve quality, reduce cost, boost operational efficiency and improve innovation. Addressing quality includes reducing variability in processes and hence, products which the FDA embraced by introducing cGMP standards to the industry. For example, the adop-tion of Quality by Design principles leads to better, high quality process design. Efficiency initiatives like harmo-nization, standardization, integration and externalization support better manufacturing outcomes. Innovation in the sector will come from many sources, but companies are fostering it through a number of ways, including R&D collaborations, engineering new technologies and highly integrated knowledge management programs.

The Increasing Importance of BiologicsAdvances in drug development are driving industry inno-vation, especially in biopharmaceuticals and biologics. And even though some of those drugs are losing patent protection, they dont face imminent competition from generics because of the regulatory climate (biosimilars are only now being approved by U.S. regulators) and the operational difficulties associated with biopharmaceuti-cal processing. By most measures, the Biopharmaceuti-cal category has great potential to continue its mon-ey-creating ways, so in an effort to improve innovation

many organizations have shifted their drug discovery and development efforts toward biologics and other protein-based therapies and away from small-molecule compounds. Similarly, established Biopharma compa-nies are investing a great deal of capital in increasing processing capability. Baxter, for example, is making the biggest capital investment in its history spending some $1 billion on a new Albumen processing plant in Georgia.

This shift shows real promise. Recently there has been amazing growth in this sector. BCC Research (Biologic Therapeutic Drugs: Technologies and Global Markets Jan. 2015) reported in 2013 that the global biologics market reached $200.6 billion and that it was expected to grow to nearly $234 billion in 2014. By the end of 2019 the total market is expected to grow to $386.7 billion at compound annual growth rate (CAGR) of 10.6 percent. This growth can be attributed to:

Superior efficacy Premium pricing 12 year exclusivity (U.S.) Biosimilars being difficult and expensive to develop

and approve Satisfying previously unmet clinical needs



Biologics Product Development LifecycleInformation Management Throughout the Product Lifecycle

Development Informatics

Information Systems Wanted and NeededWhen it comes to the biologics product development lifecycle, information management is an imperative that cannot be ignored. Product development is comprised of five primary segments including target identification and validation, lead identification, characterization and optimization, safety and preclinical, and manufacturing and regulatory. Underlying these segments are R&D tasks, activities associated with clinical elements, data gathering and analytical activities, as well as tasks associated with the processing and commercial production of the drug.

Development Informatics systems need to support all these areas and activities and at the same time link to the applications of the other areas upstream and down-stream in the process. Development Informatics is also part of the unique overall BIOVIA Biologics solution that covers Discovery, Development and Manufacturing. To explore the uptake and efficacy of information technolo-gies in support of biopharmaceutical operations, BIOVIA partnered with Pharmaceutical Manufacturing magazine (PhM) to survey leading biopharmaceutical manufac-turers to better understand current biopharmaceutical product and process development challenges.

The Most Challenging Given that in biopharmaceutical manufacturing the process is the product, the 111 surveyed R&D, QA/QC, manufacturing, operational and compliance executives rightly ranked Bioproduction Optimization as the num-ber one challenge when it comes to biologic development processes. Among the other choices (Regulatory, Quality and Compliance, Document and Data Management and Sample Management) all were ranked similarly with no particular challenge a clear leader.

BIOVIA interprets this to mean that as an organiza-tion, it is important to focus on supporting all of the challenge areas equally.

From a process perspective, the survey participants made it very clear that bioproduction optimization and quality and compliance do have the highest need of improvement and support. Documentation, data and sample management are perceived as less challenging to study respondents, but only as a matter of degree because all the areas are important.

Development Data Delayed? It DependsDo respondents believe that It takes too long to inter-pret data critical to biopharmaceutical product devel-opment? Here, responding executives are split nearly 50/50, something that is notable because in BIOVIAs experience, the delay in obtaining critical data has been identified as a real bottleneck by many, but the studys next query and its results may explain why half this group thinks it gets its data in a timely fashion and the other half does not.



9.2%0-24%

21.5%100%

23.1%75-99%

24.6%50-74%

21.5%25-49%

No59.3%

Yes40.7%

No49.1

Yes50.9%

No38% Yes

62%

No30%

Yes70%

Not VeryImportant 3.7%

SomewhatImportant 5.6%

Not Applicable1.9%

01020304050607080

0

10

20

30

40

50

60

23.1%75-99%

Very Important

48.2%

CriticallyImportant

17.6%

Important23.2%

67.4% 41.9% 39.5% 34.9% 60.5% 34.9%53.5%

Regulartory, quality, and compliance

management

Process and quality data aggregation and

analysis

Documentation and data management

Registration and sample workflow

Bioprocess workflowPredictive analysticsAnalysis ofbiology data

54.2% 53.3% 58.9% 55.1% 29% 43%

Support teams of the above

Leaders in information technology

Leaders in manufacturing &

operations

Leader in process development

Leaders in quality and regulartory

Leaders in research & development

Do you believe that it takes too long to interpret data critical to biopharmaceutical product devel-opment within your organization?

Process Development Rank Weighted Score

Bioproduction Optimization 1 304Regulatory, Quality and Compliance Management

2 278

Document and Data Management 3 197Sample Management 4 179Product Development

Formulation Development 1 265Process Development 2 259Drug Substance Identification/Characterization

3 240

Preformulation Characterization 4 204

Please rank the areas of your biologic development process that are the most challenging for your organization?(1 is the most challenging; 4 is the least challenging)

Study participants were asked are you using manual methods (like pen and paper and/or Excel) to support all of or part of your biopharmaceutical development process? The majority (62 percent) responded their organizations are indeed slaves to the pen or the spread-sheet as they accumulate and transmit data across the enterprise. Regarding the percentage of manual methods, almost half of the respondents indicated at least 75 percent of their biologic development process is supported by manual methods; 21 percent said 100 percent of their methods are manualand all the others, to a small percentage, rely on manual processes. According to survey respondents, about 60 percent indicated they are not us-ing informatics solutions at all to support their processes, something BIOVIA confirms from its experience introduc-ing informatics technologies to the Pharma universe.



Are you using manual methods (like pen and paper and/or Excel) to support all of or part of your biopharmaceutical development process?

9.2%0-24%

21.5%100%

23.1%75-99%

24.6%50-74%

21.5%25-49%

No59.3%

Yes40.7%

No49.1

Yes50.9%

No38% Yes

62%

No30%

Yes70%



Not Applicable1.9%

01020304050607080

0

10

20

30

40

50

60

23.1%75-99%

Very Important

48.2%

CriticallyImportant

17.6%

Important23.2%

67.4% 41.9% 39.5% 34.9% 60.5% 34.9%53.5%


management


analysis




54.2% 53.3% 58.9% 55.1% 29% 43%




operations




Are you using informatics solutions to support all or part of your biopharmaceutical develop-ment process?

9.2%0-24%

21.5%100%

23.1%75-99%

24.6%50-74%

21.5%25-49%

No59.3%

Yes40.7%

No49.1

Yes50.9%

No38% Yes

62%

No30%

Yes70%



Not Applicable1.9%

01020304050607080

0

10

20

30

40

50

60

23.1%75-99%

Very Important

48.2%

CriticallyImportant

17.6%

Important23.2%

67.4% 41.9% 39.5% 34.9% 60.5% 34.9%53.5%


management


analysis




54.2% 53.3% 58.9% 55.1% 29% 43%




operations




Approximately what percentage of your bio-pharmaceutical development process is being supported with manual methods like pen/paper and/or Excel spreadsheets?

9.2%0-24%

21.5%100%

23.1%75-99%

24.6%50-74%

21.5%25-49%

No59.3%

Yes40.7%

No49.1

Yes50.9%

No38% Yes

62%

No30%

Yes70%



Not Applicable1.9%

01020304050607080

0

10

20

30

40

50

60

23.1%75-99%

Very Important

48.2%

CriticallyImportant

17.6%

Important23.2%

67.4% 41.9% 39.5% 34.9% 60.5% 34.9%53.5%


management


analysis




54.2% 53.3% 58.9% 55.1% 29% 43%




operations




Which areas of your biopharmaceutical development process are currently supported by informatics solutions? (multiple answers permitted)

9.2%0-24%

21.5%100%

23.1%75-99%

24.6%50-74%

21.5%25-49%

No59.3%

Yes40.7%

No49.1

Yes50.9%

No38% Yes

62%

No30%

Yes70%



Not Applicable1.9%

01020304050607080

0

10

20

30

40

50

60

23.1%75-99%

Very Important

48.2%

CriticallyImportant

17.6%

Important23.2%

67.4% 41.9% 39.5% 34.9% 60.5% 34.9%53.5%


management


analysis




54.2% 53.3% 58.9% 55.1% 29% 43%




operations




Enter InformaticsOf those companies that do use informatics to sup-port biopharmaceutical development processes, some 67 percent say they use the technology to analyze biology data. Documentation and Data Management (60.5 percent) and Process and Quality Data Aggre-gation and Analysis (53.5 percent) followed, reveal-ing that the analysis and management of data and documentation are most supported by informatics solutions. This result helps explain why data interpre-tation is not perceived as a challenge by half of the studys respondents. Interestingly, Sample Workflow and Regulatory, Quality and Compliance Management garnered lower usage scores, even though quality is considered one of the key goals for many life science organizations and a challenge on the biologics devel-opment level as demonstrated by the responses to the survey. This may reveal that an informatics solution for this area might serve a companys compliance strategy. At the very least these key activities are supported by an electronic system.

Project Tracking in Real TimeHow important is it to your organization to be able to deliver Real Time Project Tracking and Collabora-tion with various groups involved in the development process? Respondents generally agreed this function-ality is key for almost everybody (about 90 percent).

This is no surprise as both are basic for efficiency and innovation two major goals of the life science industry.

Responses to the question: Who do you feel would benefit from a comprehensive software suite to help manage the complex process of developing and commercializing biologic drug therapies? indicated, interestingly enough, that Supporting Teams and IT leaders would benefit least. This was a bit surprising



How important is it to your organization to access real-time project tracking and col-laboration with various groups involved in the development process?

9.2%0-24%

21.5%100%

23.1%75-99%

24.6%50-74%

21.5%25-49%

No59.3%

Yes40.7%

No49.1

Yes50.9%

No38% Yes

62%

No30%

Yes70%



Not Applicable1.9%

01020304050607080

0

10

20

30

40

50

60

23.1%75-99%

Very Important

48.2%

CriticallyImportant

17.6%

Important23.2%

67.4% 41.9% 39.5% 34.9% 60.5% 34.9%53.5%


management


analysis




54.2% 53.3% 58.9% 55.1% 29% 43%




operations




Who do you feel would benefit from a comprehensive software suite to help manage the complex process of developing and commercializing biologic drug therapies? (Please check all that apply)

9.2%0-24%

21.5%100%

23.1%75-99%

24.6%50-74%

21.5%25-49%

No59.3%

Yes40.7%

No49.1

Yes50.9%

No38% Yes

62%

No30%

Yes70%



Not Applicable1.9%

01020304050607080

0

10

20

30

40

50

60

23.1%75-99%

Very Important

48.2%

CriticallyImportant

17.6%

Important23.2%

67.4% 41.9% 39.5% 34.9% 60.5% 34.9%53.5%


management


analysis




54.2% 53.3% 58.9% 55.1% 29% 43%




operations




because in BIOVIAs experience, IT and supporting teams do benefit, and to a large degree. Ultimately, the leadership in R&D, Quality/Regulatory, Process Development and Manufacturing & Operations, as well as Support Teams and Information Technology, all can benefit from a comprehensive solution.

Process Challenges Have Business ImpactWhen informatics arent applied well or integrated to serve the entire enterprise, biologics process chal-lenges can have a real impact on business. Difficulty understanding high volume sequencing data or creat-ing collaboration among groups could be an innova-tion killer. Inefficient paper-based workflows, manual data transcription and tedious manual data manage-ment often lead to low productivity. Ponderous data

access and difficulties sharing it often limits col-laboration, and the compliance risks associated with being unable to demonstrate the quality and reliabil-ity of data are also well known. When an organization cant track projects in real time or lack insight into scale-up, cycle times will suffer, constraining opera-tions and impacting speed-to-market.

BIOVIAs Biologics Development solution can benefit any biopharmaceutical enterprise. BIOVIAs dedicated solution supports all aspects of the experiment work-flow. (As a true multi-discipline system, it can even go beyond covering the requirements for chemistry too.). The solution integrates BIOVIAs Electronic Lab Notebook capabilities with a Bioregistration system, an inventory management solution for materials and con-sumables, and an instrument inventory management



Biologics Process Challenges and Business Impact

Challenges Business Impact

Understand high-volume antibody sequence data, genealogy and link of data entities

Hindered collaboration

Innovation barrier

Inefficient, paper-based workflows

Non-value add manual data transcription

Manual data management with tedious policies

Low productivity and efficiency

Difficult data access and sharingLittle collaboration

No reliable, provable data quality and integrity

No consistent and comparable processesHigh compliance risk

No real-time project tracking

Insight into bioprocess scale-upLong cycle times

solution that includes metrology. BIOVIAs end-to-end solution covers Discovery, Development and Manufac-turing and the Quality aspects of Biologic processing. Heres how:

Faster, better innovation through easier and bet-ter understanding of processes and enabled tech transfer between the different domains upstream and downstream.

Increased productivity and efficiency by removing non-value-added activities inherent in inefficient paper-based workflows, automating the manage-ment of the scientific data and by streamlining the experiment creation and reporting.

Improved collaboration through easy retrieval of data from different sources and data silos with-

out having to move the data from their original location and by the access to data from different groups within the organization as well as exter-nally with collaborators like Contract Research Organizations or Contract Manufacturing Organi-zations.

Regulatory compliance improvement through standard work practices and processes and improved data quality and integrity as well as reduced errors.

Real-time project tracking and faster decision making by better insight on data allows for reduced cycle times.

Ultimately, the solution helps to drive innovation and bring products to market faster.



Capabilities and Business Value

Capabilities Business Value

Easier and better understanding of processes

Enabled tech transferFaster & better innovation

Removed inefficient paper-based workflows

Automated data management

Streamline experiment creation and reporting

Increased productivity and efficiency

Easy retrieval of data from different sources

Access to data internally and externallyImproved collaboration

Standard work practices and processes

Improved data quality and integrity, reduced errorsImproved regulatory compliance

Real-time project tracking

Faster decision making by better insight on dataReduced cycle times



CREATING AN INTEGRATED ELECTRONICWORK FLOWThe lifecycle of an analytical method spans from meth-od development through method validation to method execution for sample analysis. The process involves numerous experiments, reports and data/document reviews over the complete lifecycle. Traditionally, dif-ferent systems, including paper and electronic, handle discrete parts of the process. As a result, extensive manual data transcription, verification and final review are required. In collaboration with BIOVIA, a major branded pharma companys informatics team designed an integrated electronic flow using existing features of the BIOVIA Workbook such as vault workflow, Empower adapter, integration with Instrument Management and Lab Execution System and Pipeline Pilot reporting. A cost/benefit analysis of this integrated workflow was done as well.

Among its business goals, the pharmaceutical man-ufacturer sought to support an expanded portfolio of molecules, an increase in early-stage work and to foster more late stage successes and less attrition. The initia-tive was also driven by compliance goals in an effort to pursue FDA critical path initiatives while demonstrating better process understanding. Ultimately, the companys overarching desire was to ensure compliance was part of an aligned corporate compliance strategic objective.

Business StrategyTo attain the initiatives goals, BIOVIAs customer pursued productivity gains by examining workflows, improving processes and deploying productivity tools. Reducing dependence on paper processes, leveraging prior experi-ence in development and using in-silico approaches were all understood to support the productivity gains required to meet its business strategy and improve compliance by eliminating opportunities for error and neglect, capturing information securely while improving review and oversight.

Information Management StrategyThe pharmaceutical companys information manage-ment strategy was simple: capture and secure informa-tion (data and its context) at the time of its creation. Data and its context are most relevant and understood when its created. Changing context to record data reduces its fidelity; information needs to be useful and reusable. With BIOVIAs solution, the companys opera-tional teams are better equipped to organize informa-tion to maximize its use in decisions and help reduce or eliminate rediscovery or reinvention. With BIOVIAs Biologics solution the companys managers can mine electronic information to find new insights, leverag-ing integrated information including information from unrelated workflows and disparate sources to improve decision making.

COMPLIANCE & QUALITY More rigorous execution of methods Automated data capture Uniformity of workflow and presentations

within notebooks Imbedded calculations and review by

exception Data traceability Cross PD availability of data and information Improved SOP adherence

PRODUCTIVITY Electronic workflow (standard process,

standard structure) Electronic review Global visibility and search capability Experiment and data reuse rather than

reinvention Re-use of chemistry, formulation

and methods Standardization and reduced

environmental complexity

COSTS & BUSINESS RISKS Reduced material costs Avoided staff and administrative costs Greater IP security Improved process understanding Improved data management and

archiving Integrity of Informatics Improved Process Execution

Informatics Delivered Dramatic Benefits:

CASE STUDY A GLOBAL PHARMACEUTICAL R&D COMPANY

About Dassault SystmesDassault Systmes, the 3DEXPERIENCE Company, provides business and people with virtual universes to imagine sustainable innovations. Its world-leading solutions transform the way products are designed, pro-duced, and supported. Dassault Systmes collaborative solutions foster social innovation, expanding possi-bilities for the virtual world to improve the real world. The group brings value to over 190,000 customers of all sizes, in all industries, in more than 140 countries. BIOVIA provides a scientific collaborative environment for advanced biological, chemical and materials experi-ences. The sophisticated enterprise system of modeling, simulation, laboratory, and quality management enables innovation for science-based industries.

For more information, visit:www.3ds.com/products-services/biovia/


This whitepaper, as well as the previously released recorded presentation and industry survey conducted by Pharmaceutical Manufacturing were sponsored by BIOVIA (formerly Accelrys). To learn more about Informatics from BIOVIA, see the following links:

Click here to view the full results of the Biologics Development survey

Click here for the Biologics Development recorded webinar

Click here for the BIOVIA Biologics Datasheet

Click here for the BIOVIA Biologics Development Datasheet

Click here for the BIOVIA Biologics Development Video Overview

Dassault Systmes175 Wyman StreetWaltham, Massachusetts02451-1223USABIOVIA Corporate AmericasBIOVIA 5005 Wateridge Vista Drive,San Diego, CA 92121USA


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