2007 Annual Meeting Programming: RS

Highlights and Discussions

One of the Regulatory Sciences (RS) Section’s goals is to provide a forum to discuss the
impact of emerging scientific developments and technologies on product registration.
Therefore, the RS Section has compiled an excellent program for the 2007 Annual
Meeting to be held in San Diego. The RS technical program at the 2007 Annual Meeting
has spanned the entire field of pharmaceutical development to provide the knowledge and
scientific information necessary to influence the regulatory processes that will influence
the availability of the medically necessary therapeutic arsenal in the 21st century.

Two primary themes that will be covered in the 2007 RS programming will be the
application of process analytical technology (PAT) and quality by design (QbD)
principles in product manufacture and regulation, and the development of chemistry and
manufacturing control (CMC) dossiers to facilitate international product marketing.

PAT and QbD

Challenges and Opportunities for the Implementation of QbD (Tuesday PM,

Roundtable)

The RS Section developed a roundtable to address the application of the PAT and QbD
principles. Many companies have adopted the approaches/principles and many others are
waiting to evaluate what all this means to pharmaceutical development in general.
Considerable investments need to be made by the companies to adopt these principles
and the overall value (return on investments) still needs to be evaluated and understood.
Although many companies have successfully implemented PAT applications in their
manufacturing processes, the future still bears some uncertainty.

Regulatory Relief from PAT and QbD: Does it Truly Exist? (Wednesday, Sunrise
Session)

Implementation of the QbD starts from the early stage of drug development in the
laboratory to gain a thorough mechanistic understanding of pharmaceutical process as
well as key product quality attributes and define the design space. This paradigm, while
not totally new, still has major impact on all areas of drug development including drug
substance, drug product, and analytical development. Having a clear understanding of
how to implement the concepts of PAT and QbD in real world applications will be of
enormous help to pharmaceutical scientists. Such an understanding will facilitate the
opportunity to take full advantage of this US Food and Drug Administration (FDA)
initiative and to develop innovative pharmaceutical processes, achieve regulatory
approval, and reap the purported benefits. A Sunrise Session is planned to update the
audience with the status of PAT from regulator’s perspective, its global utility, and the
impact on all areas of drug development, regulatory filing process, and postapproval
change process.

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Impact of Quality by Design on Pharmaceutical and Analytical Development
(Wednesday AM, Roundtable)

Following this short course is a roundtable to discuss the opportunities and challenges
associated with the implementation of Quality by Design. For a QbD application, it is
expected that the sponsor will describe the control strategy, control space, and design
space. The agreement with FDA from both review and inspection perspectives is
essential to achieve a successful outcome. The sponsors will need to develop robust
quality systems, which support QbD and encourage continuous innovation. It is expected
that successful implementation of these approaches, along with a mechanistic
understanding of drug product manufacturing processes, will provide the sponsors with
regulatory flexibility. Industry members that participated in the pilot program will
discuss their experiences.

The Science and Regulation of QbD (Wednesday PM, Roundtable)

FDA’s initiative on pharmaceutical cGMPs for the 21st century is intended to encourage
early adoption of new technologies through risk-based approaches by the pharmaceutical
industry. The ultimate goal is to reduce cost and cycle time, and improve efficiency.
Pharmaceutical development using QbD methodology under PAT framework is one of
the ways to achieve this goal. The pharmaceutical industry continues to increase
knowledge of manufacturing processes by implementing concepts such as of QbD and
PAT. A roundtable is planned to discuss the science and regulations of QbD.

The CMC Dossier

Challenges and Opportunities in Developing Drug Substances and Product CMC

Dossiers: Common Technical Document (CTD) Submissions (Sunday, Short
Course)

A short course is targeted to better understand and define drug substance and drug
product CMC information required in New Drug Application (NDA) and European
marketing authorization applications. Presentations will include global
“recommendations” on drug substance and drug product CMC information, per the
current FDA and European Medicines Agency (EMEA) drug substance and drug product
guidances, along with industry, FDA, and EMEA perspectives. Overall, this short course
should help in understanding drug development, expectations for CTD submissions, and
provide a comprehensive understanding of the current regulatory expectations. This short
course should help in developing an advanced understanding of expectations in
developing the Quality/CMC sections of CTD submissions. Additionally, it would
facilitate scientists to understand regulatory CMC expectations in the drug substance and
drug product sections of dossiers.

Risk-Based CMC Review and Quality Assessment: How Well Is It Working?

(Monday PM, Symposium)

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The short course on this topic is complemented by this Monday symposium that
elaborates the risk-based CMC review and quality assessment, which will provide
discussions both from the agency and industry perspectives regarding the risk-based
CMC review practices. Insights will be provided on outcomes from the FDA pilot
program to streamline drug product review practices. Risk-based regulatory scrutiny,
based on risk-based CMC review, necessitates a high level of scientific understanding of
product composition and manufacturing process. In the current review system, product
quality and performance are primarily established and confirmed by end-product testing.
The present review system places little or no scrutiny on how the design of an effective
manufacturing process, drug product specifications, and acceptance criteria are adequate
to ensure product quality. With the introduction of QbD principles and PAT in
manufacturing processes, companies can better assess and monitor critical drug product
attributes and product performance. Since the FDA has moved to a risk-based CMC
review in 2004, several companies have gained considerable experience via the FDA
pilot program for review of CMC information.

Issues of General Regulatory Importance

Development and Regulatory Challenges for Drug-Device Combination Products

(Tuesday AM, Symposium)

Because of the advancement of medical and pharmaceutical science/technology, modern

devices are combining the device and drug delivery technologies to offer better treatment
options for complicated disease conditions. One example of this is the drug-eluting stents.
However, such combination products pose a number of significant technical and
regulatory challenges because of complex science and technology as well as lack of clear
regulatory guidance. This symposium, composed of speakers from the FDA and industry,
is designed to discuss the developmental and regulatory challenges for such combination
products.

Clinical and CMC Regulatory Considerations in Pediatric Drug Development

(Tuesday AM, Roundtable)

The absence of regulatory guidelines adds complications and challenges to the

development of pediatric drug products. Regulatory agencies in the United States and the
European Union (EU) now require that, for drugs that are indicated in the pediatric
population, studies be conducted in that population so that such drugs can be
appropriately labeled for use in children. In the past, prescribers needed to rely on
estimating appropriate dosages of approved medications for pediatric patients from
approved dosage regiments in adults without appropriate supporting clinical studies in the
pediatric population. Regulatory agencies recognize the use of a population
pharmacokinetics as a viable approach for extrapolating safety and efficacy in children
from adequate and well-controlled studies in adults.

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Clinical Supplies and Their Stability Evaluation: Scientific Insights for Drug
Development and Regulatory Expectations in the United States and European
Union (Wednesday PM, Symposium)

A thorough and objective stability evaluation of clinical supplies and development

batches of drug substances and drug products are critical during the development stages.
Critical evaluation of stability data of the drug products and drug substances provide
insight into performance of analytical methods, drug product formulations, processes for
drug substance, and drug product manufacture and are major contributors to the
continued drug development process. This symposium will address the regulatory
requirements for stability evaluation of clinical supplies in the United States and the
European Union, need for critical stability evaluation beyond the minimum requirements,
and how effective utilization of stability data can contribute to a fast-paced drug
development process.

Biosimilar/Biogenerics

Review of Regulatory Pathway (Thursday AM, Roundtable)

To serve our members working with Biosimilar or Biogenerics products, a roundtable

discussion will be held to review regulatory challenges involved in developing follow-on
protein products, and explore their regulatory mechanisms, review, and approval
pathways.