Altasciences

In this issue, we review the key considerations and regulatory guidance for nonclinical cell and gene therapy development, including expert approaches to mitigating complex challenges, improving study efficiency, and maximizing translational opportunities to first-in-human trials.

CHAPTERS:

- 00:07 — About This Audiobook

- 01:57 — Introduction

- 05:34 — Species Selection

- 09:00 — Germline Mitigation Studies

- 13:22 — Planning Your Nonclinical Studies

- 14:44 — Case Study 1

- 17:18 — Case Study 2

- 19:08 — Conclusion

Click here to read Issue 36: https://www.altasciences.com/sites/default/files/2023-09/The-Altascientist-Issue36-Cell-and-Gene-Therapy.pdf

Traditional approaches modulate the course of disease but do not provide a cure, particularly in the case of monogenic diseases, which are caused by mutations in single genes that a person is born with. It is estimated that there are greater than 6,000 monogenic diseases, affecting over 350 million people worldwide. For these diseases, cell and gene therapy may provide hope for a cure.

There are significant challenges associated with the successful development of these complex, leading-edge therapies. Challenges involved in the in vivo preclinical study of cell and gene therapies include understanding on- and off-target activity, immune responses, and other serious adverse events. All of these must be carefully monitored, rigorously assessed, and managed to the highest extent possible.

About Altasciences:

Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

The demand for HPAPIs has been increasing over the past decade, mainly driven by oncology research. The overall HPAPI market is predicted to reach $31.5 billion USD by 2029, with more than 25% of drugs currently on the market formulated with HPAPIs.

In this issue, we examine the intricacies involved in manufacturing highly potent active pharmaceutical ingredients, herein referred to as HPAPIs. This examination of HPAPIs includes a review of the relevant guidance, classification systems, and safety processes. We also delve into how CDMO facilities, equipment, and processes for HPAPIs should be adapted to maximize safety and success for your development projects.

CHAPTERS:

- 00:08 ― Introduction

- 01:35 ― Defining High Potency for an API

- 03:47 ― Determining Exposure Potential

- 05:47 ― Engineering Controls for HPAPI Manufacturing

- 08:25 ― Regulatory Requirements for HPAPI Production

- 14:22 ― Altasciences Case Study

- 17:25 ― Conclusion

Click here to read Issue 35: https://www.altasciences.com/sites/default/files/2023-08/The-Altascientist_issue35_HPAPI.pdf

About Altasciences:

Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

Understanding a novel drug's PK and PD properties begins with nonclinical studies and evolves through early phase clinical trials. In this issue, we take a closer look at the collection and use of PK/PD data in early phase drug development.

CHAPTERS:

- 0:08 — Introduction to Issue 34

- 1:32 — Nonclinical Studies

- 2:39 — IND Requirements and Translation to Clinical PK/PD

- 5:37 — Translating Nonclinical Knowledge of PK/PD Analyses to Clinical Study

- 8:51 — Case Study

- 12:32 — Conclusion

Click here to read Issue 34: https://www.altasciences.com/sites/default/files/2023-08/the-altascientist-issue-34-toxicokinetics-pharmacokinetics-and-pharmacodynamics.pdf

Introduction on TK, PK, and PD Data:

The understanding of a new drug’s absorption, distribution, metabolism, and excretion (more commonly known as ADME) is critical to ensure that it is safe for human use. That understanding is achieved through collection and analysis of pharmacokinetic (PK) and pharmacodynamic (PD) data, which together account for approximately 25% of the contents of a drug package insert or label.

The characterization of PK/PD effects starts with nonclinical toxicokinetic (TK) studies in animals. The purpose of TK studies is to define the chemical properties of the drug, including pharmacology and toxicology, and to assist in development of downstream clinical protocols. The necessary nonclinical studies are conducted before submission of Investigational New Drug (also known as IND) applications to the FDA or other global regulatory agencies, and deliver critical data used to set the parameters for future clinical trials.

About Altasciences:

Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

A consideration with a measurable impact on early phase clinical studies is the location where trials are performed; this is especially true for first-in-human trials. Conducting early phase clinical research on novel compounds in Canada can provide significant advantages versus other locations.

CHAPTERS:

- 0:43 — Introduction

- 2:41 — Canadian Clinical Trials: Time and Cost Savings

- 3:03 — CTA in Canada vs. IND in the USA

- 4:36 — CTA in Canada vs. CTA in the EU

- 6:41 — Regulatory Review Process Predictability

- 8:57 — Business Efficiency Cost Savings

- 10:07 — Clinical Trial Participants

- 11:45 — FAQs

- 16:47 — Why Altasciences?

Read along with this PDF version:

About Altasciences:

Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

In this issue, we explore the miniature swine as an option in small and large molecule studies.

The choice of species for nonclinical safety studies is an important step in the drug development process. The species to be used is, to a large extent, dependent on the test article type and clinical indication. Existing regulatory guidance documents—combined with careful consideration of the characteristics of the drug being developed, guided by scientific, ethical, and practical considerations—help inform this key decision.

The most common non-rodent species involved in nonclinical safety studies are nonhuman primates (also referred to as NHPs) and dogs. There is, however, an increasing body of evidence that supports the use of miniature swine as a viable non-rodent option for nonclinical safety studies.

Chapters:

- 1:09 — Introduction

- 2:54 — Miniature Swine as a Viable Option for Nonclinical Safety Studies

- 8:12 — Miniature Swine Size Considerations

- 9:13 — Real-World Examples of Miniature Swine Use in Clinical Development

- 10:28 — Species Selection Criteria and Processes

- 13:10 — Case Studies

- 22:09 — How Altasciences Can Help

- 23:36 — Altasciences' Experience With Miniature Swine Studies

The different parts of the nervous system (or CNS for short), including the brain and spinal cord, and the peripheral nervous system, are important drug targets for many serious diseases affecting human health. As the body’s processing center, the CNS is responsible for all functions of our bodies, including thoughts, emotions, memories, and behaviors. Unsurprisingly, drugs working on the CNS are subject to stringent regulatory requirements, and specialized safety assessments are often mandated. To confirm CNS activity without safety concerns, dedicated nonclinical and early phase clinical studies, with relevant endpoints and biomarkers, and supporting bioanalysis, are needed; and drug manufacturing must be carefully managed via rigorous handling and production processes.

Engaging at the outset with a fully integrated and experienced drug development partner can ensure safety, with timely sharing of data at every step of the drug development plan, and facilitate agile, flexible decision-making and planning.

CHAPTERS:

- 1:22 — Introduction

- 3:53 — Preclinical Safety and Toxicity Testing of CNS-Active Molecules

- 12:28 — Preclinical Case Study

- 15:11 — Manufacturing CNS-Active Drugs for Trials and Commercialization

- 21:48 — CDMO Case Study

- 24:39 — Maximizing Early Phase Clinical Trials of CNS-Active Drugs

- 34:02 — Clinical Case Study

- 36:27 — Bioanalysis for CNS Drug Development (Preclinical to Phase IV)

- 42:26 Altasciences' CNS Center of Excellence

In this issue, we describe the numerous benefits of incorporating a stable isotope labelled internal standard for quantitative liquid chromatography-mass spectrometry, and detail recent advances in MS technology. Several case studies are presented, which exemplify novel bioanalytical workflows that are required to meet the challenges faced in both non-clinical and clinical development, across a variety of drug classes.

- 0:42 Introduction

- 5:33 The Case for Stable Isotope Labelled Internal Standards for LCMS Quantitation

- 8:34 Recent Innovations in Mass Spectrometry

- 15:38 Case Study: Dried Blood Microsampling

- 17:14 Case Study: Anti-Epileptic Drug Panel

- 19:17 Case Study: COVID-19 Neutralizing Monoclonal Antibody

- 21:16 Case Study: Differential Mobility Spectrometry (DMS)

- 23:49 Case Study: Bioequivalence

- 26:22 Case Study: Oligonucleotides

- 33:57 Conclusion

Click here to download a readable, PDF version of Issue 13: https://www.altasciences.com/sites/default/files/2022-12/The-Altascientist-issue-30-LCMS.pdf

About Altasciences:

Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

In this issue of The Altascientist, we lead you on the complex, multi-step data journey for Phase I clinical trials, from conceptualization and initial protocol development, collection and analysis, through final regulatory submission. We highlight best practices and approaches to mitigate challenges, and show how integration and collaboration build the strongest datasets for your drug development program.

Quality, reliable data is the key to successful drug development. From the initial preclinical data, the plan to bring a drug to market is built upon the foundation of solid, reliable data that demonstrates safety in a human patient population.

In this issue:

- 0:19 Introduction

- 1:01 Protocol Development

- 2:49 Data Management

- 9:07 Statistical Support

- 10:49 Analysis and Reporting

- 13:28 Conclusion

Click here to download a readable, PDF version of Issue 29: https://www.altasciences.com/sites/default/files/2022-12/The-Altascientist-issue-29-Data-Journey.pdf

About Altasciences:

Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

Liquid-filled hard-shell capsules are a popular formulation for oral solid delivery of chemical drugs and nutraceuticals. Often selected for drugs with poor solubility and/or poor bioavailability, liquid-filled hard-shell capsules also have applications in a number of other situations, including specific benefits during early phase clinical development.

In this issue of The Altascientist, you will hear about:

• 0:57 — Applications of liquid-filled hard-shell capsules

• 5:32 — The production process

• 8:13 —The role of excipients

• 9:54 — Other advantages of liquid-filled hard-shell capsules

• 11:04 —Case study

Click here to download a readable, PDF version of Issue 28: https://www.altasciences.com/sites/default/files/2022-10/The-Altascientist_issue-28_LFCs.pdf

About Altasciences:

Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

Podcast—Nonclinical Considerations When Developing An Ophtalmic Drug by The Altascientist