2014 ne conference presentation by rick calabrese

Best Quality Practices for Biomedical Research in Drug Development

Rick Calabrese Global Director of Quality Systems Sartorius Stedim Biotech 15 Jan 2014

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ASQ Northeast Pharmaceutical GMP Conference 2014

Table of Contents

• Project Background • Purpose of Technical Report • Project Goals • Objectives • Current Technical Report Outline • Management System • Documentation • Technical Requirements • Legal & Ethical Considerations • Dependencies & Resources • Contributors & Affiliation • Looking Ahead • Questions


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Project Background


• Recent basic science achievements promise significant payoffs in human health, but these potential benefits are threatened by low productivity -- measured by the high costs and high risks of failure in the current development processes and the declining number of successful products reaching patients.”

• FDA’s “Critical Path Paper”, March 2004

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Project Background

• Because of the rapid progress of biological sciences, non-GLP laboratory research (e.g. biomarker development, exploratory, mechanistic studies etc.) has become increasingly critical for modern drug development.

• Many research institutions are recognizing the need to establish solid quality standards to ensure integrity and validity of the data they generate. But which standards and how to introduce them is the big question.

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Project Background

• Non-GLP biomedical research has traditionally been considered to be off-limits for formal quality systems or management.

• Scientists in general regard their work as a highly intellectual activity where quality is a knowledge and experience driven integral part of the scientific rigor they apply.

• A long-standing tradition of quality control in science has been peer review of the results, but modern pharmaceutical research has become so complex that peer review has a limited value today.


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Purpose of Technical Report

• To minimize waste of resources and reduce the need for costly confirmation and repetition of work already performed

• To generate reliable data to ensure a solid basis for deciding whether to invest in further development of a strategy or product

• Quality means better science


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• The technical report specifies the general quality requirements for non-regulated biomedical research in drug development in order to ensure credibility of biomedical research results.

• This includes both large and small molecule discovery and non-clinical development that is not covered by GxP.

• It is based on the format laid out for the international quality management standard ISO 9001.

Technical Report Project


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Project Goals • The target audience for this technical report is the scientific staff

at institutions and companies involved in drug development.

• Compliance with applicable regulatory and safety requirements are not covered by this report.

• Set up basic quality standards for new drug development.


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Objectives

• Publish ASQ Technical Report (Completed June 2012) • Publish the technical report Mandarin and Spanish • Present information to targeted groups • Publish promotional papers in ASQ journals and other magazines • Provide training courses on the information in the technical

report • Initiate joint forums with WHO and regulatory agencies (FDA,

EMA, Health Canada, SFDA, etc.) for their input and by in. • Develop the technical report into an ASQ/ANSI standard • Turn the ASQ/ANSI standard into an internationally recognized

ISO standard.


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Current Technical Report Outline

• Management System • Documentation • Technical Requirements • Legal and ethical considerations


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Management System

• Have managerial and scientific personnel to carry out their duties

• Have arrangements and / or policies to ensure that it may not adversely affect the quality of their work

• Appoint a member of staff as quality manager who has direct access to the highest level of the research institute’s management at which decisions are made on research institution policy or resources

• Have facilities and equipment sufficient to conduct the study


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• Prescriptive documents typically include Standard Operating Procedures (SOPs), methods, study plans or protocols.

• They are critical for ensuring data quality and integrity as well as overall repeatability of the research work.

• Descriptive documents include batch records, reports and forms. • All laboratory activities should be documented to contain

sufficient detail to allow replication of the original work. • Ensure traceability by identifying raw data, calculations,

identification numbers for samples, reagents, reference standards, etc.

• Non-conforming results should be clearly identified and fully explained in the primary record.

• Deviations should be investigated explaining their impacts on the study.


Documentation

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Documentation • Research institutions should establish procedures for the

control of prescriptive and descriptive documents. • Procedures should include a formal review and approval. • Only the most recent approved documents are available for

staff use. • The research institution should establish and maintain a

change control process. • Documents should be stored in a secure and suitable

environment that provides confidentiality and prevention from loss, deterioration and destruction.


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Technical Requirements

• Personnel • Facility and Infrastructure • Test Equipment • Equipment Design • Calibration • Test Methods • Method Validation • Sampling and Chain of Custody • Materials • Test Articles, Control Articles, and Test Systems


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Personnel • Training is critical to develop and maintain competence.

• All personnel should be made aware of the importance of training and its impact on the quality objectives.

• Training should be carried out by personnel with appropriate skills, qualifications and experience.

• Records are typically kept to document the qualifications of the personnel used as trainers.


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Facility and Infrastructure

• Buildings and workspace • Utilities, such as controlled temperature storage facilities, purified

water, steam, and compressed air, bottled gases • Storage areas for the test and/or control article • Computer and communications networking • Equipment to ensure the safety of staff and the integrity of test

systems and reference standards • Premises designed and equipped to afford maximum protection

against the entry of insects or other animals • Limited or restricted access to prevent the entry of unauthorized

people


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Test Equipment

• Designed, located and maintained to suit its intended purpose. • Constructed so that surfaces should not be reactive, additive, or

absorptive so as to affect the test method or test results. • Designed so that it can be easily and thoroughly cleaned. • Repair and maintenance operations should not negatively affect

test results. • Installed in such a way as to reduce the likelihood of

contamination. • Defective equipment should, if possible, be removed from active

use.


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Equipment Design


• Equipment shall be suitably located to facilitate operations for its intended use and for its cleaning and maintenance.

• Equipment shall be of adequate size and constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.

• Substances required for operation, such as lubricants or coolants, shall not come into contact with components, drug product containers, closures, in-process materials, or drug products.

• Repair and maintenance should not negatively affect test results.

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Calibration


• Calibrated, verification through time of use, suitability checks, or both at specific intervals and/or prior to use against measurement standards traceable to international or national measurement standards.

• Labeling of units calibration status and date of recalibration.

• Safeguarded from adjustments that may invalidate the measurement results.

• Protected from damage and deterioration during handling, maintenance, and storage.

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Test Methods • Methods to perform scientific work should be documented to allow for

reproducibility.

• They should be clear and easy to understand.


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Method Validation

• Validation of methods used is critical for the integrity and authenticity of study results.

• Wherever possible, published and generally accepted standard methods should be used.

• Research institutions should confirm and document first that it can properly and reliably operate these standard methods before using them.

• Internally developed methods may also be used if they are appropriate for the intended use, and that documented evidence shows that it meets the appropriate levels of precision, accuracy, repeatability and robustness.

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Sampling and Chain of Custody


• Adequate and correct sampling is critical for ensuring that the sample taken is a true representative of the whole.

• The research institution should therefore have a sampling plan and procedures for collecting samples of substances, materials, or products for subsequent testing.

• Utilization of sampling (AQL) plans such as ANSI Z1.4

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Materials

• Handling, storage and quality of materials used in the conduct of biomedical research can affect the outcome.

• The identity and purity of the material received must meet method specifications.

• Manufacturer identifier (such as lot or batch numbers) • In-house labeling is used to provide traceability • Materials are stored under the appropriate conditions • Usage of the materials is tracked


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Test Articles, Control Articles, and Test Systems • The purity, concentration, and stability of test articles and

control articles (where used) can greatly affect the outcome and repeatability of a study or an experiment.

• The purity, concentration, stability and storage of test articles and control articles should be specified and evaluated and documented periodically following standard operating procedures.


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Legal and Ethical Considerations

• Protection of intellectual property • Vendor selection and qualification • Research institutions may outsource a portion of their

research activities to a third party. The subcontracted work may be subject to the research institution’s quality system.

All personnel involved in biomedical research activities are to act in an ethical manner free from research

misconduct, US FDA 42 CFR Part 93


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Dependencies and Resources

QSBRDD

Technology

Personnel

Other Services Distribution

Promotion


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Contributors and Affiliation

George Bernstein MAI Consulting Rick Calabrese Sartorius-Stedim North America Inc.

Keith Conerly Sodexo

Li-Chung Huang ImClone Systems

Alice Krumenaker CorePharma,

Richard Lombardi Forest Research Institute

June Morita Consultant

Juli Moticka Regeneron

Ülo Palm Forest Research Institute

Michele Pruett MLP GXP Solutions LLC

Sandra R. Storli Abbott

John Surak Clemson University and Consultant

Mark Trotter Trotter Biotech Solutions

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Looking Ahead...

• When is the next milestone?

• What are the expected deliverables?

• Known risks and issues

• What is the timeline for these issues?

• What are the immediate next steps?


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Purchase a Copy of the Technical Report

● If you would like to purchase a copy of the Technical Report,

please visit the ASQ website under the Quality Press section:

http://asq.org/quality-press/


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Join the Committee

• If you would like to find out more information about the standard or

to join the committee, please contact:

Rick Calabrese at [email protected]

or

Alice Krumenaker at [email protected]


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mailto:[email protected]

mailto:[email protected]

Thank You! 31