Altasciences

Immunomodulatory drug development is trending toward increasingly complex modalities as science advances and more effective and safe immunotherapies are needed. Immunomodulatory drugs are at the forefront for the treatment of various types of cancer, infectious diseases, and numerous autoimmune diseases, including rheumatoid arthritis, type I diabetes, lupus, and multiple sclerosis. As the complexity of these therapeutics increases, so must the sophistication of the bioanalytical assays designed to either quantify them or measure their impact on the patient.

In this issue, we review common classes of immunomodulators, bioanalytical methods used to quantify them, and their associated biomarkers. We further present two scenarios that address the complexities of bioanalysis for immunomodulators and practical considerations to ensure quality bioanalysis to inform pharmacokinetic (PK), pharmacodynamic (PD), and safety data in clinical trials.

Maximizing bioavailability is a critical aspect of drug development, ensuring that the maximum therapeutic effect is achieved with the minimum dose. By rigorously evaluating and optimizing the chemical, physical, and biological properties of the API, pharmaceutical scientists can enhance bioavailability, leading to more effective and reliable medications.

In this issue, we review different analytical testing techniques that support drug product development specific to bioavailability.

Contents include:

- API characterization

- Common techniques for determining particle size distribution

- Formulation approaches to maximize bioavailability

- Case study: manufacturing of a nanosuspension

Dermal drug delivery approaches are on the rise in a variety of therapeutic areas, including reformulation of existing medications. In many instances, the improvements in delivery systems can lead to a successful 505(b)(2) application, extending the patent life of a drug for its sponsor, or creating a marketing opportunity for a company developing dermal delivery of an already marketed drug. New medications are being specifically designed for dermal delivery, and advancements in the field continue as innovative approaches are being tested for the market.

In this audiobook, we review the specific nonclinical requirements to move a dermal program forward to Phase I clinical trials, as well as the approaches and considerations that minimize inherent challenges.

Chapters:

- 1:32 — Current Trends in Dermal Delivery Systems

- 3:38 — Managing Challenges in Dermal Drug Development

- 5:43 — Species Selection for Dermal Studies

- 7:49 — Commonly Required Nonclinical Studies

- 9:02 — Dermal-Specific Studies

- 11:02 — Case Study

- 14:27 — Conclusion

Read Issue 39 instead: https://www.altasciences.com/sites/default/files/2024-04/the-altascientist-issue-39-nonlcinical-dermal-studies.pdf

Explore the key considerations for successful formulation development and manufacture for safety assessment, and learn about the strategies Altasciences employs to support sponsors.

- 0:35 — Introduction

- 3:34 — Considerations for Preclinical Drug Formulation

- 7:36 — Preclinical Drug Product Manufacturing

- 9:46 — Steps in Preclinical Drug Product Manufacturing

- 13:49 — Quality Assurance and Control

- 14:33 — Regulatory Aspects

- 15:42 — Risk Management

- 17:17 — Case Study

- 21:27 — Conclusion

Formulating and manufacturing drugs for preclinical testing is an early, crucial step toward human trials. At the preclinical stage, the goal is to maximize exposure for safety testing, formulating to the limits of solubility and maximum volumes. To optimize the formulation for preclinical testing, one must consider the route of administration, selection of excipients, stability testing, plans and options for scale-up, and contingency plans.

In this issue, we will review the applications of PCR analysis for your gene therapy programs, and present two case studies.

Click to read this audiobook: https://www.altasciences.com/sites/default/files/2023-10/the-altascientist-issue-37-pcr_4.pdf

Gene therapy continues to accelerate through preclinical and clinical research arenas. These programs are developed with targeted and personalized medicines in mind. The goal of gene therapy is to safely deliver and incorporate a genetic alteration to restore or repair the protein of a missing or faulty gene. Preclinical assessments of gene therapies consider the general absorption, distribution, metabolism, and excretion of the drug, as well as data from tailored assessments to evaluate delivery and cell incorporation.

Gene therapies require, by design and definition, DNA and/or RNA delivery and analysis. While most ongoing research involves gene therapies being delivered in vivo via adeno-associated viral (AAV) vectors, new in vivo delivery mechanisms are on the rise, such as other types of delivery vectors including lipid nanoparticles.

CHAPTESR:

- 0:05 — About Issue 37

- 1:20 — Introduction to qPCR, dPCR, and RT-PCR

- 5:58 — Utility of qPCR, ddPCR, and RT-PCR

- 8:19 — PCR Applications

- 10:01 — Advantages and Applications

- 17:45 — Case Study 1

- 20:20 — Case Study 2

- 22:47 — Conclusion

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 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

- 3:12 — Canadian Clinical Trials: Time and Cost Savings

- 3:46 — CTA (Health Canada) vs. IND (FDA)

- 5:17 — CTA: Health Canada vs. EMA

- 7:52 — Regulatory Review Process Predictability

- 10:19 — Business Efficiency Cost Savings

- 11:28 — Clinical Trial Participants

- 13:06 — FAQs

- 18:43 — 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