Current Topics in Nonclinical Drug Development: Volume 1
暫譯: 非臨床藥物開發當前議題：第一卷

《非臨床藥物開發當前議題》系列的首卷探討了非臨床藥物開發中的關鍵問題和當前主題。本卷涵蓋了從化合物特徵到藥物註冊的藥物開發中的各個主題和策略。由該領域的多位專家撰寫，並討論了技術的最新快速進展及相關的法規指導變化。

其他特色包括：
- 處理研究設計、結果評估和數據呈現中的日常問題。
- 解釋醫療器械開發中的新方法。
- 包含專門章節，探討生物資訊學在藥物開發中的應用。
- 討論藥物的光安全性測試策略。

《非臨床藥物開發當前議題，第一卷》將幫助毒理學家、毒理病理學家、顧問、監管機構、研究主任及非臨床科學家處理研究設計、結果評估和數據呈現中的日常問題。此外，本書將成為追求與非臨床藥物開發相關研究的學者和研究生的重要參考資料。

Pritam S. Sahota, Global ToxPath LLC, Kennewick, Washington, USA,

has extensive experience in toxicologic pathology and drug development

within the framework of nonclinical safety assessment of pharmaceuticals.

Dr. Sahota was previously Executive Director and Head of Pathology,

Preclinical Safety, at Novartis Pharmaceuticals, East Hanover, New Jersey.

He obtained his veterinary medicine (BVSc) and veterinary pathology

degrees (MSc and PhD) from Punjab Agricultural University, India. He

is a diplomate of the American Board of Toxicology. After receiving his

PhD in 1976, he started working as a toxicologic pathologist at Dawson

Research Corporation (DRC), Orlando, Florida, a contract research organization

involved in the preclinical safety evaluation of drugs and chemicals.

At DRC, he received increasing responsibility over the next 10 years

(toxicologic pathologist, senior toxicologic pathologist, and scientific director).

As a scientific director, he was responsible for the scientific aspects of

pathology as well as toxicology at DRC. While working briefly for Dynamac

Corporation, Research Triangle Park, North Carolina (1986-1987), he conducted

retrospective scientific audits of 23 NTP carcinogenicity studies and

participated in discussions with the representatives of NTP, FDA, and EPA

to review the results of scientific audits of over 200 NTP carcinogenicity

studies. In 1987, he joined Ciba-Geigy Pharmaceuticals in New Jersey as

Head/Manager of pathologists in preclinical safety and was also responsible

for establishing pathology peer review, quality control, and scheduling

systems. He continued to work primarily in this position with increasing

responsibilities at Ciba-Geigy and then Novartis Pharmaceuticals (after

Ciba-Sandoz merger in 1997) to become director and eventually Executive

Director and Head of pathology. During this time, he also served as an international

project team representative for a number of successfully marketed

CNS, immunosuppression, diabetes, and cardiovascular drugs, including

Diovan, which eventually became one of the 15 all-time, best-selling prescription

drugs. He also held an adjunct academic appointment of Assistant

Professor at the University of Medicine and Dentistry, New Jersey, for

8 years. He successfully led several global preclinical safety initiatives at

Novartis, including patient centricity, review of best practices in cardiotoxicity

and ocular toxicity, as well as evaluation of rodent carcinogenicity

potential based on noncarcinogenicity data to minimize future delays in

regulatory submissions. Since retirement from Novartis Pharmaceuticals

in 2012, Dr Sahota has been the President of Global ToxPath LLC located

in Kennewick, WA, USA (Toxicologic Pathology Consultancy). As lead editor,

he published the following books with CRC Press/Taylor & Francis:

(1) Toxicologic Pathology: Nonclinical Safety Assessment (First Edition,

2013); (2) Toxicologic Pathology: Nonclinical Safety Assessment (Second

Edition, 2018); (3) The Illustrated Dictionary of Toxicologic Pathology and

Safety Science (First Edition, 2019); (4) CT-NCDD: Volume 1 (due to be

published in 2020); (5) Road to Greatness (due to be published in 2020);

(6) Toxicologic Pathology: A Primer (due to be published in 2021); and

(7) Toxicologic Pathology: An Atlas (due to be published in 2022).

Philip Bentley is a principal consultant at Toxicodynamix International

LLC. He studied biochemistry at the University of Hull, UK, graduating

with a BSc in 1970 and a PhD in 1974. He had postdoctoral fellowships at

the Universities of Basel, Switzerland, and Mainz, Germany. His postdoctoral

research centered upon formation and inactivation of reactive metabolites

and the enzymes involved in the metabolism of foreign compounds. In

1979, he joined the Investigative Toxicology group (known as Cell Biology)

in the Toxicology Department of Ciba-Geigy, Basel, Switzerland, and

remained with the company, later Novartis, until 2014. In these 35 years,

he held various management positions in Europe and the United States

with responsibility for Investigative Toxicology; Drug Metabolism; Drug

Metabolism and Toxicology; Preclinical Safety Europe; Drug Metabolism

and Pharmacokinetics; Toxicology/Pathology United States; Preclinical

Safety United States; and Global Preclinical Safety. In these positions, he

contributed to the registration of more than 45 marketed drug products and

the preparation of several hundred investigational new drugs (INDs). He

has vast experience in the areas of drug metabolism and disposition, toxicology/

pathology, genetic toxicology, pharmacokinetics/toxicokinetics,

and all aspects of investigative toxicology. He is well grounded in biochemistry,

cell biology, molecular biology, and pharmacology with the ability to

integrate data from the different preclinical disciplines to enable translation

to determine the clinical relevance of the findings. He is very familiar with

global drug registration requirements and working on global projects.

He has authored more than 80 scientific publications, has lectured

in toxicology at the University of Basel for more than 30 years, and is a

past president of the European Society of Biochemical Pharmacology

and the Swiss Society of Toxicology. He was a member of the PhRMA/IQ

Preclinical Leadership (DruSafe) Committee for 16 years, a member of the

advisory board of the PSTC Biomarker consortium, and a member of the

expert working group for revision of the ICH S2 guidance on genotoxicity

testing and the PhRMA expert group on genotoxic impurities.

Zbigniew W. Wojcinski is president of Toxicology & Pathology Consulting,

LLC, in Ann Arbor, Michigan, and has over 30 years of experience in drug

development. Dr. Wojcinski received his undergraduate degree (BSc) in

Zoology from the University of Toronto and his DVM and DVSc (Pathology)

degrees from the Ontario Veterinary College, University of Guelph. He is a

board-certified diplomate of the American Board of Toxicology and a diplomate

of the American College of Veterinary Pathologists. He is also recognized

as a specialist in Veterinary Pathology by the Canadian Veterinary

Medical Association. Dr Wojcinski gained experience in drug development

and toxicologic pathology during his 22-year tenure with Parke-Davis\

Warner-Lambert and Pfizer Global Research and Development and then 31/2

years with Fulcrum Pharma Developments, Inc. In 2011, he founded Drug

Development Pathology Services, LLC in Ann Arbor, Michigan, and subsequently

grew the organization into Drug Development Preclinical Services,

LLC to provide toxicology, pathology, and drug metabolism and pharmacokinetic

services. Dr Wojcinski has extensive experience as a study director,

study pathologist, and review pathologist for numerous acute and repeated

dose toxicity studies, including carcinogenicity studies. Throughout his

career, he has managed successful cross-functional drug development

teams in CNS, metabolic diseases, and dermatology therapeutic areas. As

therapeutic area leader for Dermatology at Pfizer, Dr Wojcinski was responsible

for development and implementation of the safety and risk management

strategies for, what was then, a new therapeutic area. He has also

been directly involved in the preparation of pre-IND documents, nonclinical

safety assessments for IND/IMPD/NDA/MAA, investigator's brochures,

and labeling (USPI, SmPC) negotiations in CNS, anti-infective, and dermatology

therapeutic areas. Dr Wojcinski has had numerous interactions with

regulatory agencies in the United States, Europe, Canada, and Australia for

compounds at various stages of development. He has also provided pathology

consultation and histopathology peer review on several projects in various

therapeutic areas, including respiratory infections, dermatitis, ophthalmic

disease, anticancer, and hypolipidemics, and served on Pathology Working

Groups. Dr Wojcinski is a full member of numerous professional societies

including the American College of Veterinary Pathologists, Society

of Toxicologic Pathologists, Society of Toxicology, American College of

Toxicology, American Veterinary Medical Association, Canadian Veterinary

Medical Association, Canadian Association of Veterinary Pathologists,

Regulatory Affairs Professionals Society, and Roundtable of Toxicology

Consultants. He has served as president of the Dermal Toxicity Specialty

Section of the Society of Toxicology, an associate editor for the Society of

Toxicologic Pathology, editor of The Scope for the Society of Toxicologic

Pathology, and chair of the Society of Toxicologic Pathology Recruitment

Subcommittee. Dr Wojcinski has lectured at the Ontario Veterinary College

and the University of Maryland and authored/coauthored numerous scientific

reports, manuscripts, and book chapters. Recently, he was coeditor

for The Illustrated Dictionary of Toxicologic Pathology & Safety Science (First

Edition, published in 2019) and is currently contributing editor for Road to

Greatness (due to be published in 2020); coeditor for Toxicologic Pathology:

A Primer (due to be published in 2021); and coeditor for Toxicologic Pathology:

An Atlas (due to be published in 2022).

Pritam S. Sahota, Global ToxPath LLC, 肯納威克，華盛頓州，美國，

在藥物的非臨床安全評估框架內擁有豐富的毒理病理學和藥物開發經驗。

Sahota博士曾擔任諾華製藥公司（Novartis Pharmaceuticals）新澤西州東漢諾威的病理學執行董事及病理學部門負責人。

他在印度旁遮普農業大學獲得獸醫學（BVSc）及獸醫病理學學位（碩士及博士）。

他是美國毒理學委員會的認證專家。1976年獲得博士學位後，他開始在佛羅里達州奧蘭多的道森研究公司（Dawson Research Corporation, DRC）擔任毒理病理學家，該公司是一家專注於藥物和化學品的非臨床安全評估的合同研究機構。

在DRC，他在接下來的10年中逐漸獲得更多責任（毒理病理學家、高級毒理病理學家及科學主任）。

作為科學主任，他負責DRC的病理學及毒理學的科學方面。在短暫為北卡羅來納州研究三角公園的Dynamac公司工作期間（1986-1987），他進行了23項NTP致癌性研究的回顧性科學審核，並參與與NTP、FDA及EPA代表的討論，以審查超過200項NTP致癌性研究的科學審核結果。1987年，他加入新澤西州的Ciba-Geigy製藥公司，擔任非臨床安全病理學部門的病理學主管/經理，並負責建立病理學同行評審、質量控制及排程系統。他在Ciba-Geigy及隨後的諾華製藥（1997年Ciba-Sandoz合併後）主要在此職位工作，並逐漸增加責任，最終成為病理學部門的主任及執行董事。在此期間，他還擔任多個成功上市的中樞神經系統（CNS）、免疫抑制、糖尿病及心血管藥物的國際項目團隊代表，包括Diovan，該藥物最終成為15種歷史上最暢銷的處方藥之一。他還在新澤西州醫學與牙科大學擔任助理教授的兼任學術職位達8年。他成功主導了諾華的幾個全球非臨床安全倡議，包括以病人為中心、心臟毒性及眼毒性的最佳實踐審查，以及基於非致癌性數據評估啮齒動物的致癌潛力，以最小化未來在監管提交中的延遲。自2012年從諾華製藥退休以來，Sahota博士一直擔任位於華盛頓州肯納威克的Global ToxPath LLC（毒理病理學顧問）的總裁。作為主編，他與CRC Press/Taylor & Francis出版了以下書籍：

(1) 毒理病理學：非臨床安全評估（第一版，

2013）； (2)毒理病理學：非臨床安全評估（第二版，

2018）； (3) 毒理病理學與安全科學插圖詞典（第一版，2019）； (4) CT-NCDD：第一卷（預計於2020年出版）；

(5)通往偉大的道路（預計於2020年出版）；

(6)毒理病理學：入門（預計於2021年出版）；及

(7)毒理病理學：圖集（預計於2022年出版）。

Philip Bentley 是Toxicodynamix International LLC的首席顧問。

他在英國赫爾大學學習生物化學，於1970年獲得學士學位，1974年獲得博士學位。他曾在瑞士巴塞爾大學和德國美因茨大學擔任博士後研究員。他的博士後研究集中於反應性代謝物的形成和失活以及參與外源化合物代謝的酶。1979年，他加入瑞士巴塞爾的Ciba-Geigy毒理學部的調查毒理學小組（稱為細胞生物學），並在該公司（後來的諾華）工作至2014年。在這35年間，他在歐洲和美國擔任多個管理職位，負責調查毒理學、藥物代謝、藥物代謝與毒理學、歐洲非臨床安全、藥物代謝與藥物動力學、毒理學/病理學（美國）、非臨床安全（美國）及全球非臨床安全。在這些職位上，他為超過45種上市藥物的註冊及數百種研究新藥（IND）的準備做出了貢獻。他在藥物代謝與處置、毒理學/病理學、遺傳毒理學、藥物動力學/毒物動力學及所有調查毒理學的各個方面擁有豐富的經驗。他在生物化學、細胞生物學、分子生物學及藥理學方面有扎實的基礎，能夠整合來自不同非臨床學科的數據，以便轉化為臨床相關性。他對全球藥物註冊要求及全球項目工作非常熟悉。他已發表超過80篇科學出版物，在巴塞爾大學教授毒理學超過30年，並曾擔任歐洲生化藥理學會及瑞士毒理學會的前任會長。他曾是PhRMA/IQ非臨床領導（DruSafe）委員會的成員16年，PSTC生物標記聯盟的顧問委員會成員，以及ICH S2遺傳毒性測試指導方針修訂的專家工作組成員及PhRMA遺傳毒性雜質專家小組的成員。

Zbigniew W. Wojcinski 是位於密歇根州安娜堡的毒理學與病理學顧問公司（Toxicology & Pathology Consulting, LLC）的總裁，擁有超過30年的藥物開發經驗。Wojcinski博士在多倫多大學獲得動物學學士學位，並在圭爾夫大學的安大略獸醫學院獲得獸醫學（DVM）及獸醫病理學（DVSc）學位。他是美國毒理學委員會的認證專家及美國獸醫病理學學會的專家。他還被加拿大獸醫醫學協會認可為獸醫病理學專家。Wojcinski博士在Parke-Davis/Warner-Lambert及Pfizer全球研究與開發工作22年，隨後在Fulcrum Pharma Developments, Inc.工作3年半，積累了藥物開發及毒理病理學的經驗。2011年，他在密歇根州安娜堡創立了藥物開發病理學服務公司（Drug Development Pathology Services, LLC），並隨後將該組織發展為藥物開發非臨床服務公司（Drug Development Preclinical Services, LLC），提供毒理學、病理學及藥物代謝與藥物動力學服務。Wojcinski博士在多項急性及重複劑量毒性研究（包括致癌性研究）中擔任研究主任、研究病理學家及審查病理學家，擁有豐富的經驗。在他的職業生涯中，他管理了多個成功的跨功能藥物開發團隊，涵蓋中樞神經系統、代謝疾病及皮膚病治療領域。作為Pfizer皮膚病治療領域的領導者，Wojcinski博士負責開發及實施當時新治療領域的安全及風險管理策略。他還直接參與了IND前文件的準備、IND/IMPD/NDA/MAA的非臨床安全評估、研究者手冊及中樞神經系統、抗感染及皮膚病治療領域的標籤（USPI, SmPC）談判。Wojcinski博士與美國、歐洲、加拿大及澳大利亞的監管機構在不同開發階段的化合物上有過多次互動。他還在多個治療領域的幾個項目中提供病理學諮詢及組織病理學同行評審，包括呼吸道感染、皮膚炎、眼科疾病、抗癌及降脂藥物，並擔任病理學工作組成員。Wojcinski博士是多個專業學會的正式成員，包括美國獸醫病理學學會、毒理病理學學會、毒理學學會、美國毒理學學會、加拿大獸醫醫學協會、加拿大獸醫病理學學會、監管事務專業協會及毒理學顧問圓桌會議。他曾擔任毒理學學會皮膚毒性專業小組的會長、毒理病理學學會的副編輯、《毒理病理學學會的範疇》的編輯及毒理病理學學會招聘小組的主席。Wojcinski博士曾在安大略獸醫學院及馬里蘭大學講授課程，並撰寫/共同撰寫了多篇科學報告、手稿及書籍章節。最近，他是毒理病理學與安全科學插圖詞典（第一版，2019年出版）的共同編輯，並目前擔任通往偉大的道路（預計於2020年出版）的貢獻編輯；毒理病理學：入門（預計於2021年出版）的共同編輯；及毒理病理學：圖集（預計於2022年出版）的共同編輯。