Part of the MaRS Best Practices Series. Speaker: Valentia Lee-Brotherton, PhD, Ashuren. This session, led by seasoned industry experts, will explore how to effectively set up your pre-clinical POC studies, address pre-clinical safety requirements and issues, and give you an overview of the manufacturing standards required for Phase I studies.
More information: http://www.marsdd.com/Events/Event-Calendar/Best-Practices-Series/ind-05132008.html
This presentation is a brief overview of ICH-GCP guidelines. Although ICH-GCP is a very vast topic, still this presentation will cover almost all the points. The reader will be able to discuss about the roles and responsibilities of various personnel in clinical trials.
Webinar Series on Demystifying Phases in Clinical Trials & COVID-19 Updates organized by Institute for Clinical Research (ICR), NIH
Speaker: Dato Dr Chang Kian Meng, Haematologist from Sunway Medical Centre
More information, please visit: https://clinupcovid.mailerpage.com/resources/p9f2i7-introduction-to-phase-2-3-trial-s
This presentation is a brief overview of ICH-GCP guidelines. Although ICH-GCP is a very vast topic, still this presentation will cover almost all the points. The reader will be able to discuss about the roles and responsibilities of various personnel in clinical trials.
Webinar Series on Demystifying Phases in Clinical Trials & COVID-19 Updates organized by Institute for Clinical Research (ICR), NIH
Speaker: Dato Dr Chang Kian Meng, Haematologist from Sunway Medical Centre
More information, please visit: https://clinupcovid.mailerpage.com/resources/p9f2i7-introduction-to-phase-2-3-trial-s
Quality Risk management in pharmaceutical Industry. A general Review on Risk analysis and Risk assessment in pharmaceutical Industry as it is prescribed by GMP regulations of WHO, ICH, FDA.
Introduction to Expectedness/Unexpectedness Assessment in Drug Safety & Pharmacovigilance of Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Drug Safety & Pharmacovigilance - Introduction - Katalyst HLSKatalyst HLS
Introduction to Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Regulatory authorities (US-FDA, WHO and ICH)Sagar Savale
To promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner.
With respect to such products, protect the public health by ensuring that the food are safe, Wholesome, sanitary, and properly labelled; human and veterinary drugs are safe and effective; there is reasonable assurance of the safety and effectiveness of devices intended for human use; cosmetics are safe and properly labelled, and public health and safety are protected from the electronic product radiation.
Participates through appropriate process with representatives of other countries to reduce the burden of regulation, harmonize regulatory requirements, and achieve appropriate reciprocal arrangements.
Estimating the Maximum Safe Starting Dose for First-in-Human Clinical TrialsMaRS Discovery District
Part of the MaRS BioEntrepreneurship series session: Clinical Trials Strategy
Speaker: Beatrice Setnik
This is available as an audio presentation:
http://www.marsdd.com/bioent/feb12
Also view the event blog and summary:
http://blog.marsdd.com/2007/02/14/bioentrepreneurship-clinical-trial-strategies-its-never-too-soon/
Quality Risk management in pharmaceutical Industry. A general Review on Risk analysis and Risk assessment in pharmaceutical Industry as it is prescribed by GMP regulations of WHO, ICH, FDA.
Introduction to Expectedness/Unexpectedness Assessment in Drug Safety & Pharmacovigilance of Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Drug Safety & Pharmacovigilance - Introduction - Katalyst HLSKatalyst HLS
Introduction to Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Regulatory authorities (US-FDA, WHO and ICH)Sagar Savale
To promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner.
With respect to such products, protect the public health by ensuring that the food are safe, Wholesome, sanitary, and properly labelled; human and veterinary drugs are safe and effective; there is reasonable assurance of the safety and effectiveness of devices intended for human use; cosmetics are safe and properly labelled, and public health and safety are protected from the electronic product radiation.
Participates through appropriate process with representatives of other countries to reduce the burden of regulation, harmonize regulatory requirements, and achieve appropriate reciprocal arrangements.
Estimating the Maximum Safe Starting Dose for First-in-Human Clinical TrialsMaRS Discovery District
Part of the MaRS BioEntrepreneurship series session: Clinical Trials Strategy
Speaker: Beatrice Setnik
This is available as an audio presentation:
http://www.marsdd.com/bioent/feb12
Also view the event blog and summary:
http://blog.marsdd.com/2007/02/14/bioentrepreneurship-clinical-trial-strategies-its-never-too-soon/
Drug Development Life Cycle - Costs and RevenueRobert Sturm
Presentation explains the Drug Development Process in terms of time/costs from initial research to final manufacturing. It presents strategies for increasing profits/decreasing costs, shows the impact of generics and details how Information Technology fits into this equation. It uses research from DiMasi and Grabowski to identify drug costs and product revenue.
Speaker: Anne Tomalin, BA, BSc, RAC (US, CAN & EU), President of CanReg Inc.
Topics Addressed
* Planning ahead to add credibility and value with your partners, investors and outside experts
* What is the landscape of various filings for a drug, a medical device or a diagnostic device?
* Developing a multi-disciplinary project team to manage your regulatory strategy:
o Different strategies for different products
o How to formulate a sound path to drug development decision-making
* What is needed for approval of a medical device
* The preclinical studies required for an IND filing
* The multiple components of the actual IND submission
* Management and communication between the teams assembling the IND
o When to outsource and bring in consultants
* Interacting with the regulatory authority
Download an audio file of this presentation at:
http://www.marsdd.com/bioent/jan15
Aligning Global Regulatory Strategy to Decrease Approval Time in Emerging Mar...NAMSA
Aligning Global Regulatory Strategy to Decrease Approval Time in Emerging Markets is the first of many Remote Training Series that NAMSA does. This first series discusses and evaluates emerging markets and the opportunities and challenges that follow.
La economía en el Paraguay y el Río de la Plata hacia comienzos del siglo XVIIIManu Pérez
Dentro de la región conocida como litoral rioplatense, las relaciones movilizaban diversos productos como el azúcar, el vino, tabaco, cera, tejidos, algodón y yerba mate, producto este último en el cual el Paraguay venía especializándose desde comienzos del siglo XVII. Simultáneamente, en el siglo XVIII, gracias a la creciente capacidad mercantil de Buenos Aires para poder controlar los flujos de intercambio regionales, se fue acentuando un proceso de ‘‘atlantización’’ de la economía rioplatense, el cual se consolidaría durante el último tercio de la centuria con las Reformas Borbónicas.
TetraQ - Integrated Preclinical Drug Development Solutions Presentationguest55305
TetraQ is a leading Australian preclinical contract research organization focused on providing a broad range of integrated preclinical drug development solutions in the disciplines of ADME, Bioanalytics, Efficacy, Toxicology and Pharmaceutics. TetraQ’s Toxicology, ADME and Bioanalytics laboratories are GLP recognised and in collaboration with NATA, TetraQ’s ADME team pioneered ISO17025-2005 (R&D) research & development accreditation becoming the first laboratory in Australia to obtain this accreditation in 2005.
Each of our world-class facilities is equipped with state-of-the-art instrumentation including LC-MS/MS, HPLC & ELISA. Essentially, TetraQ is a one-stop-shop for early stage drug development and we are recognized as world leaders in bioanalytical method development & sample analysis of drugs / metabolites in biological fluids with both human and animal samples.
The Pistoia Alliance is examining the challenges of the Faster Safe Companion Diagnostics (CDx) by Aligning Discovery & Clinical Data in the Regulatory Domain.
The slides discuss whether the data standards used in the research environment be aligned better with the data standards used in the regulated environment? If so, the time and cost of the development of NGS-based CDx could be reduced.
Well-trained clinical research professionals are in high demand. The tremendous increase in medical technology and information in the last decade has resulted in an explosion of potential new drugs, devices and biologics that must be tested before being released for use by the public. The profession is constantly challenged to improve and streamline the clinical research programs in order to shorten the development timelines and control the cost for new product development
“The Evolution of Pharmaceutical Biotechnology – Science, Strategies, Products, and Regulations”
Shows the latest developments in pharmaceutical biotechnology and provides a broad overview of biotherapeutic & biosimilar regulations globally and in the EU
Biomarkers to Diagnostics – The Essential Tool Box for Drug Development - Presentation delivered by Johan Luthman, Vice President, Neuroscience Clinical Development, Eisai Pharmaceuticals at the marcus evans Evolution Summit Fall 2015 in Las Vegas
PAREXEL Early Phase Clinical Research Services experts discuss developing trends in drug development including adaptive trials design, real-world data and biomarkers.
FDA 2013 Clinical Investigator Training Course Preparing an IND Application: ...MedicReS
FDA 2013 Clinical Investigator Training Course Preparing an IND Application: Preclinical Considerations for Cell and Gene Therapy Products
Patrick Au, Ph.D., (CBER)
Currently worth a few million dollars, the emerging organs-on-chips market has the potential to become a multi-billion dollar market.
Organs-on-chips: the promise of solving one of the pharmaceutical industry’s major hurdles
Bringing a new drug to market is one of the longest and most costly paths any industry has to walk. Companies start with several thousands of compounds that may have positive effects against a disease or a human condition. More than twelve years and several billion dollars later, if they’re lucky they managed to get one of these compounds onto the market. All the others failed at one stage or another during the drug development process – and the later the failure, the more expensive it is. Current methods – cell culture in petri dishes and animal testing among others – are not predictive enough. Around 90% of drugs that have been validated on these models then fail during clinical trials because of toxicity or lack of efficacy. The pharmaceutical industry therefore needs more predictive tools to make drug candidates fail earlier and cheaper. Other industries where toxicity testing is a major concern, such as cosmetics, agro-food and consumer goods, also need such solutions, in particular because animal testing is now banned for these industries in certain geographical areas. Several options have been envisioned, the most promising of which is certainly organs-on-chips. These combinations of micro-technology and biology reconstitute the physiological and mechanical functions of human organs under the form of micro-engineered devices lined with living cells. Precisely controlled fluid flows combined with mechanical cues and tissue-tissue interfaces enable dynamic models, much more relevant than conventional static cell cultures. As a sign of confidence in this technology, significant funding has been allocated to organs-on-chips developers: DARPA and the NIH respectively awarded $140M and $76M over 5-year periods to support developments. In parallel, technology developers have raised more than $80M since 2012 with investors. In Yole Développement’s report, all the key elements to understand the organs-on-chips landscape are detailed.
For more information, please visit our website: https://www.i-micronews.com/reports.html
Don Tapscott's New Solutions for a Connected Planet - MaRS Global LeadershipMaRS Discovery District
In this new age of networked intelligence, collaborative communities are enhancing and even bypassing crumbling institutions. We are innovating the way our financial institutions and governments operate; how we educate our children; how the healthcare, newspaper, and energy industries serve their customers; how we care for our neighbourhoods; and even how we solve global problems.
From his latest book, (co-author Anthony D. Williams) Macrowikinomics: New Solutions for a Connected Planet, Don Tapscott presents groundbreaking innovations from every corner of the globe: how businesses, organizations and individuals alike are using mass collaboration to revolutionize not only the way we work, but how we live, learn, create and care for each other.
SR&ED: What you need to know about the changing landscape - MaRS Best PracticesMaRS Discovery District
The Scientific Research and Experimental Development (SR&ED) tax incentive program provides support in the form of tax credits to groups or individuals conducting scientific research or experimental development in Canada.
Some significant changes are on the way as a result of the last federal budget. See how these new rules could affect you!
what is the best method to sell pi coins in 2024DOT TECH
The best way to sell your pi coins safely is trading with an exchange..but since pi is not launched in any exchange, and second option is through a VERIFIED pi merchant.
Who is a pi merchant?
A pi merchant is someone who buys pi coins from miners and pioneers and resell them to Investors looking forward to hold massive amounts before mainnet launch in 2026.
I will leave the telegram contact of my personal pi merchant to trade pi coins with.
@Pi_vendor_247
What website can I sell pi coins securely.DOT TECH
Currently there are no website or exchange that allow buying or selling of pi coins..
But you can still easily sell pi coins, by reselling it to exchanges/crypto whales interested in holding thousands of pi coins before the mainnet launch.
Who is a pi merchant?
A pi merchant is someone who buys pi coins from miners and resell to these crypto whales and holders of pi..
This is because pi network is not doing any pre-sale. The only way exchanges can get pi is by buying from miners and pi merchants stands in between the miners and the exchanges.
How can I sell my pi coins?
Selling pi coins is really easy, but first you need to migrate to mainnet wallet before you can do that. I will leave the telegram contact of my personal pi merchant to trade with.
Tele-gram.
@Pi_vendor_247
how to swap pi coins to foreign currency withdrawable.DOT TECH
As of my last update, Pi is still in the testing phase and is not tradable on any exchanges.
However, Pi Network has announced plans to launch its Testnet and Mainnet in the future, which may include listing Pi on exchanges.
The current method for selling pi coins involves exchanging them with a pi vendor who purchases pi coins for investment reasons.
If you want to sell your pi coins, reach out to a pi vendor and sell them to anyone looking to sell pi coins from any country around the globe.
Below is the contact information for my personal pi vendor.
Telegram: @Pi_vendor_247
what is the future of Pi Network currency.DOT TECH
The future of the Pi cryptocurrency is uncertain, and its success will depend on several factors. Pi is a relatively new cryptocurrency that aims to be user-friendly and accessible to a wide audience. Here are a few key considerations for its future:
Message: @Pi_vendor_247 on telegram if u want to sell PI COINS.
1. Mainnet Launch: As of my last knowledge update in January 2022, Pi was still in the testnet phase. Its success will depend on a successful transition to a mainnet, where actual transactions can take place.
2. User Adoption: Pi's success will be closely tied to user adoption. The more users who join the network and actively participate, the stronger the ecosystem can become.
3. Utility and Use Cases: For a cryptocurrency to thrive, it must offer utility and practical use cases. The Pi team has talked about various applications, including peer-to-peer transactions, smart contracts, and more. The development and implementation of these features will be essential.
4. Regulatory Environment: The regulatory environment for cryptocurrencies is evolving globally. How Pi navigates and complies with regulations in various jurisdictions will significantly impact its future.
5. Technology Development: The Pi network must continue to develop and improve its technology, security, and scalability to compete with established cryptocurrencies.
6. Community Engagement: The Pi community plays a critical role in its future. Engaged users can help build trust and grow the network.
7. Monetization and Sustainability: The Pi team's monetization strategy, such as fees, partnerships, or other revenue sources, will affect its long-term sustainability.
It's essential to approach Pi or any new cryptocurrency with caution and conduct due diligence. Cryptocurrency investments involve risks, and potential rewards can be uncertain. The success and future of Pi will depend on the collective efforts of its team, community, and the broader cryptocurrency market dynamics. It's advisable to stay updated on Pi's development and follow any updates from the official Pi Network website or announcements from the team.
NO1 Uk Divorce problem uk all amil baba in karachi,lahore,pakistan talaq ka m...Amil Baba Dawood bangali
Contact with Dawood Bhai Just call on +92322-6382012 and we'll help you. We'll solve all your problems within 12 to 24 hours and with 101% guarantee and with astrology systematic. If you want to take any personal or professional advice then also you can call us on +92322-6382012 , ONLINE LOVE PROBLEM & Other all types of Daily Life Problem's.Then CALL or WHATSAPP us on +92322-6382012 and Get all these problems solutions here by Amil Baba DAWOOD BANGALI
#vashikaranspecialist #astrologer #palmistry #amliyaat #taweez #manpasandshadi #horoscope #spiritual #lovelife #lovespell #marriagespell#aamilbabainpakistan #amilbabainkarachi #powerfullblackmagicspell #kalajadumantarspecialist #realamilbaba #AmilbabainPakistan #astrologerincanada #astrologerindubai #lovespellsmaster #kalajaduspecialist #lovespellsthatwork #aamilbabainlahore#blackmagicformarriage #aamilbaba #kalajadu #kalailam #taweez #wazifaexpert #jadumantar #vashikaranspecialist #astrologer #palmistry #amliyaat #taweez #manpasandshadi #horoscope #spiritual #lovelife #lovespell #marriagespell#aamilbabainpakistan #amilbabainkarachi #powerfullblackmagicspell #kalajadumantarspecialist #realamilbaba #AmilbabainPakistan #astrologerincanada #astrologerindubai #lovespellsmaster #kalajaduspecialist #lovespellsthatwork #aamilbabainlahore #blackmagicforlove #blackmagicformarriage #aamilbaba #kalajadu #kalailam #taweez #wazifaexpert #jadumantar #vashikaranspecialist #astrologer #palmistry #amliyaat #taweez #manpasandshadi #horoscope #spiritual #lovelife #lovespell #marriagespell#aamilbabainpakistan #amilbabainkarachi #powerfullblackmagicspell #kalajadumantarspecialist #realamilbaba #AmilbabainPakistan #astrologerincanada #astrologerindubai #lovespellsmaster #kalajaduspecialist #lovespellsthatwork #aamilbabainlahore #Amilbabainuk #amilbabainspain #amilbabaindubai #Amilbabainnorway #amilbabainkrachi #amilbabainlahore #amilbabaingujranwalan #amilbabainislamabad
Turin Startup Ecosystem 2024 - Ricerca sulle Startup e il Sistema dell'Innov...Quotidiano Piemontese
Turin Startup Ecosystem 2024
Una ricerca de il Club degli Investitori, in collaborazione con ToTeM Torino Tech Map e con il supporto della ESCP Business School e di Growth Capital
NO1 Uk Rohani Baba In Karachi Bangali Baba Karachi Online Amil Baba WorldWide...Amil baba
Contact with Dawood Bhai Just call on +92322-6382012 and we'll help you. We'll solve all your problems within 12 to 24 hours and with 101% guarantee and with astrology systematic. If you want to take any personal or professional advice then also you can call us on +92322-6382012 , ONLINE LOVE PROBLEM & Other all types of Daily Life Problem's.Then CALL or WHATSAPP us on +92322-6382012 and Get all these problems solutions here by Amil Baba DAWOOD BANGALI
#vashikaranspecialist #astrologer #palmistry #amliyaat #taweez #manpasandshadi #horoscope #spiritual #lovelife #lovespell #marriagespell#aamilbabainpakistan #amilbabainkarachi #powerfullblackmagicspell #kalajadumantarspecialist #realamilbaba #AmilbabainPakistan #astrologerincanada #astrologerindubai #lovespellsmaster #kalajaduspecialist #lovespellsthatwork #aamilbabainlahore#blackmagicformarriage #aamilbaba #kalajadu #kalailam #taweez #wazifaexpert #jadumantar #vashikaranspecialist #astrologer #palmistry #amliyaat #taweez #manpasandshadi #horoscope #spiritual #lovelife #lovespell #marriagespell#aamilbabainpakistan #amilbabainkarachi #powerfullblackmagicspell #kalajadumantarspecialist #realamilbaba #AmilbabainPakistan #astrologerincanada #astrologerindubai #lovespellsmaster #kalajaduspecialist #lovespellsthatwork #aamilbabainlahore #blackmagicforlove #blackmagicformarriage #aamilbaba #kalajadu #kalailam #taweez #wazifaexpert #jadumantar #vashikaranspecialist #astrologer #palmistry #amliyaat #taweez #manpasandshadi #horoscope #spiritual #lovelife #lovespell #marriagespell#aamilbabainpakistan #amilbabainkarachi #powerfullblackmagicspell #kalajadumantarspecialist #realamilbaba #AmilbabainPakistan #astrologerincanada #astrologerindubai #lovespellsmaster #kalajaduspecialist #lovespellsthatwork #aamilbabainlahore #Amilbabainuk #amilbabainspain #amilbabaindubai #Amilbabainnorway #amilbabainkrachi #amilbabainlahore #amilbabaingujranwalan #amilbabainislamabad
What price will pi network be listed on exchangesDOT TECH
The rate at which pi will be listed is practically unknown. But due to speculations surrounding it the predicted rate is tends to be from 30$ — 50$.
So if you are interested in selling your pi network coins at a high rate tho. Or you can't wait till the mainnet launch in 2026. You can easily trade your pi coins with a merchant.
A merchant is someone who buys pi coins from miners and resell them to Investors looking forward to hold massive quantities till mainnet launch.
I will leave the telegram contact of my personal pi vendor to trade with.
@Pi_vendor_247
Currently pi network is not tradable on binance or any other exchange because we are still in the enclosed mainnet.
Right now the only way to sell pi coins is by trading with a verified merchant.
What is a pi merchant?
A pi merchant is someone verified by pi network team and allowed to barter pi coins for goods and services.
Since pi network is not doing any pre-sale The only way exchanges like binance/huobi or crypto whales can get pi is by buying from miners. And a merchant stands in between the exchanges and the miners.
I will leave the telegram contact of my personal pi merchant. I and my friends has traded more than 6000pi coins successfully
Tele-gram
@Pi_vendor_247
Latino Buying Power - May 2024 Presentation for Latino CaucusDanay Escanaverino
Unlock the potential of Latino Buying Power with this in-depth SlideShare presentation. Explore how the Latino consumer market is transforming the American economy, driven by their significant buying power, entrepreneurial contributions, and growing influence across various sectors.
**Key Sections Covered:**
1. **Economic Impact:** Understand the profound economic impact of Latino consumers on the U.S. economy. Discover how their increasing purchasing power is fueling growth in key industries and contributing to national economic prosperity.
2. **Buying Power:** Dive into detailed analyses of Latino buying power, including its growth trends, key drivers, and projections for the future. Learn how this influential group’s spending habits are shaping market dynamics and creating opportunities for businesses.
3. **Entrepreneurial Contributions:** Explore the entrepreneurial spirit within the Latino community. Examine how Latino-owned businesses are thriving and contributing to job creation, innovation, and economic diversification.
4. **Workforce Statistics:** Gain insights into the role of Latino workers in the American labor market. Review statistics on employment rates, occupational distribution, and the economic contributions of Latino professionals across various industries.
5. **Media Consumption:** Understand the media consumption habits of Latino audiences. Discover their preferences for digital platforms, television, radio, and social media. Learn how these consumption patterns are influencing advertising strategies and media content.
6. **Education:** Examine the educational achievements and challenges within the Latino community. Review statistics on enrollment, graduation rates, and fields of study. Understand the implications of education on economic mobility and workforce readiness.
7. **Home Ownership:** Explore trends in Latino home ownership. Understand the factors driving home buying decisions, the challenges faced by Latino homeowners, and the impact of home ownership on community stability and economic growth.
This SlideShare provides valuable insights for marketers, business owners, policymakers, and anyone interested in the economic influence of the Latino community. By understanding the various facets of Latino buying power, you can effectively engage with this dynamic and growing market segment.
Equip yourself with the knowledge to leverage Latino buying power, tap into their entrepreneurial spirit, and connect with their unique cultural and consumer preferences. Drive your business success by embracing the economic potential of Latino consumers.
**Keywords:** Latino buying power, economic impact, entrepreneurial contributions, workforce statistics, media consumption, education, home ownership, Latino market, Hispanic buying power, Latino purchasing power.
US Economic Outlook - Being Decided - M Capital Group August 2021.pdfpchutichetpong
The U.S. economy is continuing its impressive recovery from the COVID-19 pandemic and not slowing down despite re-occurring bumps. The U.S. savings rate reached its highest ever recorded level at 34% in April 2020 and Americans seem ready to spend. The sectors that had been hurt the most by the pandemic specifically reduced consumer spending, like retail, leisure, hospitality, and travel, are now experiencing massive growth in revenue and job openings.
Could this growth lead to a “Roaring Twenties”? As quickly as the U.S. economy contracted, experiencing a 9.1% drop in economic output relative to the business cycle in Q2 2020, the largest in recorded history, it has rebounded beyond expectations. This surprising growth seems to be fueled by the U.S. government’s aggressive fiscal and monetary policies, and an increase in consumer spending as mobility restrictions are lifted. Unemployment rates between June 2020 and June 2021 decreased by 5.2%, while the demand for labor is increasing, coupled with increasing wages to incentivize Americans to rejoin the labor force. Schools and businesses are expected to fully reopen soon. In parallel, vaccination rates across the country and the world continue to rise, with full vaccination rates of 50% and 14.8% respectively.
However, it is not completely smooth sailing from here. According to M Capital Group, the main risks that threaten the continued growth of the U.S. economy are inflation, unsettled trade relations, and another wave of Covid-19 mutations that could shut down the world again. Have we learned from the past year of COVID-19 and adapted our economy accordingly?
“In order for the U.S. economy to continue growing, whether there is another wave or not, the U.S. needs to focus on diversifying supply chains, supporting business investment, and maintaining consumer spending,” says Grace Feeley, a research analyst at M Capital Group.
While the economic indicators are positive, the risks are coming closer to manifesting and threatening such growth. The new variants spreading throughout the world, Delta, Lambda, and Gamma, are vaccine-resistant and muddy the predictions made about the economy and health of the country. These variants bring back the feeling of uncertainty that has wreaked havoc not only on the stock market but the mindset of people around the world. MCG provides unique insight on how to mitigate these risks to possibly ensure a bright economic future.
US Economic Outlook - Being Decided - M Capital Group August 2021.pdf
Preclinical Development Planning for Emerging Pharma and Biotech Firms
1. Accelerating Development
Preclinical Development
Planning for Emerging Pharma
and Biotech Firms
Valentia Lee-Brotherton, PhD
May 13, 2008
MaRS Workshop: From Benchtop to IND
2. Objective of Presentation
• To provide some points to consider when planning
and conducting a preclinical development program
to enable First-in-Human (FIH) studies
• Assumptions:
– Candidate selected (i.e. screening completed)
– Money in the bank (~3-4 $MM)
– Sufficient test article
– New Chemical Entity (not generic or reformulation)
3. Typical Timelines for Non-Clinical Testing
Programs
In-House Discovery
and Candidate Selection
Chemistry, Stability, (Bio) Analytical Development
Nonclinical Toxicology, Pharmacokinetics,
Safety Pharmacology
Preparation of Regulatory Documentation
Phase I Clinical Trial(s)
0 1 2 3 4 5 6 7 8 9 10 11 months
4. Challenges to the Emerging Biotech Company
• Lack of Resources • Investor Pressure
– $ – Meeting (realistic)
timelines in the face of
– Experience in product
issues (e.g., poor
development
candidate selection)
• Clearly Defined Vision
• Managing multiple
– Lack of clinical plan service providers
• Manufacturing/CMC – Contract laboratories
Issues (preclinical, analytical)
– Lack of test article – Contract manufacturer
(supply of test article)
– Formulation, scale-up
issues – Clinical CROs
– Consultants (clinical,
nonclinical, manufacturing,
regulatory affairs,
biostatistics, etc.)
5. The IND Application: A Significant Effort
• What's Needed?:
– General Investigational Plan (clinical development plans overall)
– Investigator’s Brochure (“IB”)
– Proposed Clinical Trial Protocol(s) and Investigator Information
– Chemistry, Manufacturing, and Controls Information
– Pharmacology and Toxicology Information
– Previous Human Experience
• Preparation Time
– 3-4 people, 1 month
• How Big?
– Typically 10-15 volumes (2,500-4,500 pages)
6. Getting Started
• Product Development Strategy should incorporate:
– Manufacturing
– Preclinical Pharmacology and Toxicology
– Clinical Plans (from FIH to Phase II)
– Regulatory
– Remember that all aspects are inter-related
• Budget/Resource Management
7. Approaching the Nonclinical Safety Testing
Program
• Toxicology studies should not be considered a box-
checking exercise to simply satisfy Regulators
– Contributes to the understanding of the product
– Provides the supporting data to enable FIH studies (target
organs, predict toxicology, reversibility, exposure levels,
starting doses, etc.)
8. Perspective
• Preclinical development is an expensive investment
for a small/emerging company that requires:
– A good plan/strategy that considers regulatory
expectations and the Company’s objectives
(scientific/medical and business)
– Efficient and expedient implementation by experienced
individuals
– Interpretation and positioning of results by experts
• If not designed, conducted, and/or interpreted
correctly, preclinical studies can add considerable
time and expense to a program
9. General Toxicology Program Considerations
• Regulatory expectation (21 CFR Part 312): Nonclinical
safety studies should be conducted to determine the
safety of proposed clinical trials
• Studies should be Conducted in accordance with Good
Laboratory Practice (GLP) regulations/principles
– An international quality standard
– It’s about the documentation!
– Covers personnel, facilities, equipment, operations, test article,
data entry, reports, etc.
– Does not cover interpretation or evaluation of data
– Contributes to the timing and expense of studies
– Sponsor has obligations
› Ensuring the integrity of the data - monitoring the study
10. General Toxicology Program Considerations
(cont’d)
• The preclinical development plan will depend on a
number of factors, including:
– Product type and similarity to existing agents with known
safety profiles
– Proposed indication in humans (i.e., cancer vs rheumatoid
arthritis)
– Proposed duration of administration (i.e., short term vs
chronic; dosing regimen)
– Target population (i.e., adults, infants, pregnant women,
elderly, etc.)
– Proposed route(s) of administration
– Use pattern considerations (i.e., concomitant medications,
adjuvant therapy)
11. General Toxicology Program Considerations
(cont’d)
• Studies should be designed specifically for the drug
under development
– Relevant animal species (i.e., pharmacologically active)
› Particularly for biologics / therapeutic proteins
– Knowledge of expected toxicities
› Dose range finding data and pilot studies
› Drug class effects (published literature, Freedom of
Information, E.U. EPARs, scientific meetings, etc.)
› First principles
› Interaction with regulatory authorities
12. Objectives of Early Toxicology Studies
• Identify the target organs / systems of the drug
– Monitoring in clinical trials
– Gender differences
– Expected? (based on pharmacology)
• Characterize the dose-response curve
– No-Observed-Adverse-Effect Level (NOAEL)
› Important for Maximum Recommended Starting Dose (NCE)
– Maximum tolerated dose (MTD)
– Therapeutic Index
13. Objectives of Early Toxicology Studies (cont’d)
• Characterize the toxicity
– Reversible?
– Dose-dependent?
• Assess the systemic exposure
– Calculate pharmaco-/toxicokinetics (Tmax, Cl, Vd, t½)
– Margins of safety relative to human exposures based on
AUC and Cmax
– Aid in dose selection for further animal toxicology, FIH
studies
14. Developing a Biologic is Different From a Drug
Differences between small molecules and biologics
– a generalization
Small Molecule Drug Biologic
Low molecular weight High molecular weight
Familiar antecedents Potentially unique
Known impurities Unfamiliar impurities
Often orally dosed Often parenteral, IV dosing
Maximal tolerated dose Optimal biologic dose
Meaningful chronic tox Uncertain chronic tox
Species-independent Species-specific
Biotransformed Degraded
Not immunogenic Immunogenicity issues
15. Typical IND-Enabling Preclinical Safety Studies
Species Duration of Studies Cost ($)*
(Bio)analytical Assay development 1,000/day
Validation (per species) 15,000-20,000
Running samples 70-100/sample
Dose formulation Analyses $5K/time study
Rat Single dose 29,000-75,000
7 day DRF 50,000-125,000
14 days 165,000-200,000
28 days 120,000-275,000
Dog Maximum tolerated dose (MTD) 30,000-65,000
7 day DRF 75,000-145,000
14 days 140,000-300,000
28 days 200,000-450,000
* Pricing will vary depending on the actual study design, route of administration,
numbers of groups, numbers of animals, bioanalytical determinations, special
tests required, etc.
16. Typical IND-Enabling Preclinical Safety Studies
(cont’d)
Species Type of Studies Cost ($)*
Monkey MTD 75,000-125,000
7 day DRF 100,000-240,000
14 days 265,000-410,000
28 days 280,000-550,000
Genetox Bacterial mutagenicity 6,000-8,000
Chromosome aberration 20,000-27,000
Rodent micronucleus 25,000-35,000
Safety Pharm hERG inhibition (patch clamp) ~16,000
CNS rodent 25,000-35,000
Cardiovascular (telemetry) 75,000-120,000
Respiratory 25,000-35,000
* Pricing will vary depending on the actual study design, route of administration,
numbers of groups, numbers of animals, bioanalytical determinations, special tests
required, etc.
17. Typical IND-Enabling Preclinical Safety Study
Generalized design of a repeated-dose rodent toxicity study
Treatment Dose Main (Terminal) Recovery Toxicokinetics*
Group (mg/kg/day) Male Female Male Female Male Female
Vehicle 0 10 10 5 5 0 0
Low Dose A 10 10 0 0 9 9
Mid Dose B 10 10 0 0 9 9
High Dose C 10 10 5 5 9 9
• Number of animals depends on blood volumes required, number
of timepoints, etc.
• GLP-compliance needed for a pivotal (clinical trial-supporting)
study
• Toxicokinetic evaluations
• Standard AND drug- or disease-specific endpoints
• Histopathology
18. Example 1: (NCE, Cancer Indication)
• Program
– Abbreviated, in 2 species
– Focus on repeat-dose studies (cycles of treatment)
• Issues
– Multiple salt forms (available at different times)
– Dose selection in studies (cytotoxic NCE for cancer, so
based on STD10, not NOAEL)
– 2 very different routes of administration (mechanisms of
action dependent on route)
19. Example 2 (Biologic, Non-cancer Indication)
• Program
– Full program, 2 species
– Molecular target (human)
• Issues
– Target down-regulated in healthy/normal animals/humans
(toxicology program in healthy animals? Or disease
models?)
– Test material quality (research/pre-GMP/GMP)
– Need to consider efficacy data when setting doses in
humans (MABEL approach), not just toxicology data
– Need to evaluate immunogenicity (toxicology program;
method development)
20. Strategies for Success
• Desired: a successful preclinical development program
that results in a high quality regulatory submission that
anticipates the questions of the Regulator
• Understand that the animal toxicology data impact the
clinical trial design, but the trial design can also
influence the toxicology program
• Co-ordinate Toxicology and Manufacturing
– Ensure that high-quality (ideally, GMP) product is available
(quantity, timing, quality/identity/purity/stability is documented)
• Have a regulatory strategy
– Pre-IND/Pre-CTA consultation?
– IND submission preparation co-ordinated with timing of
toxicology program?
21. Strategies for Success (cont’d)
• Become “IND-Ready”, even at the preclinical stage
of development:
– Pharmacology studies: proper reports (report numbers,
etc., and consider electronic filing)
– Regulatory toxicology considerations (GLP compliance,
etc.)
– Anticipate types of data that will be needed
– Manufacturing considerations (timing, logistics, stability
data, characterization and release of API/product, with an
eye to GMP product for trials)
22. Strategies for Success (cont’d)
• Present a high-quality submission: avoid
Regulatory “Red Flags” and address reviewer’s
expectations (content, format, quality of data to
support the proposed trial, etc.)
23. Help Needed!
• Regulatory Agency guidelines (Canada, US, EU)
• Regulatory Agency consultations (Pre-IND or Pre-
CTA meetings)
• Published commentaries, opinions, and guidance
• Meetings, Conferences, Colleagues
• Consultants
24. FDA Guidance Related to Preclinical Safety
Evaluation
• FDA Regulatory Pharmacology and Toxicology
homepage:
• www.fda.gov/cder/pharmtox/default.htm
– Links to all FDA guidance documents (draft and final)
› ICH
› FDA
– Internal policies and procedures
– Contact names of Pharm/Tox staff within CDER
• Other sources (examples)
– Oncology Drugs - DeGeorge, et al., 1998. Regulatory
consideration for preclinical development of anticancer drugs.
Cancer Chemother Pharmacol 41:173-185.
– Inhalation Drugs - DeGeorge, et al., 1997. Considerations for
toxicology studies of respiratory drug products. Regul Toxicol
Pharmacol 25:189-193.
25. THANK YOU !
Valentia Lee-Brotherton, PhD
Ashuren Health Sciences
www.ashuren.com