Altasciences

In this issue, we examine spray-dried dispersions (SDDs) as an effective method to improve solubility and bioavailability of your active pharmaceutical ingredient (API) in early-phase drug development. We review the spray drying

process, which converts a liquid into a dry powder, and how the resulting SDDs benefit from improved characteristics for further development. We also discuss the combination of spray drying with nanomilling for further bioavailability improvements and flexible downstream processing.

Additionally, we explore the applicability of testing proof-of-concept, as well as creating material for first-in-human (FIH) clinical trials. Leveraging our in-house preclinical services, we also have the unique capability to test spray-dried material versus raw API in vivo, generating meaningful data to compare with in vitro test results.

In this issue, we explore the characteristics and advantages of non-GLP discovery studies, along with emerging trends in this important early phase of drug development research.

We also present two case studies from our Sacramento site, highlighting discovery studies that assessed the biodistribution of the test article under specific experimental conditions.

In this issue of The Altascientist, we review strategies, including those implemented at Altasciences, for developing, qualifying, and implementing CRAs to assess the safety of test articles in vitro to complement in vivo preclinical safety assessment.

According to the World Health Organization, at least a billion people are currently living with vision impairment from a preventable or treatable source. The main conditions causing their distance vision impairment or blindness are cataracts, refractive error, age-related macular degeneration, glaucoma, diabetic retinopathy, and presbyopia.

Precedence Research reports that the global ophthalmic drug market size is estimated to double in 10 years, from $34.6 billion in 2021 to an estimated $68.93 billion by 2030. The development of pharmacological interventions for many of these conditions has been accelerating, supported by new delivery methods and formulation approaches. For conditions that require surgery or corrective devices, eye drops are an important part of diagnosis, and pre- and post-surgery treatment plans.

In this issue of The Altascientist, we explore how to meet the challenges of formulation development for ocular therapies.

Current and future development of glucagon-like peptide-1 receptor agonists, more commonly referred to as GLP-1 RAs, or simply as GLP-1s, involves complexities not only in formulation but in all areas of early-phase drug development. Developing and refining preclinical models for early efficacy signals, developing and validating the bioanalytical assays necessary for quantitation, and designing the clinical studies that deliver the most robust data in this innovative therapeutic area are all key elements of a drug development program.

In this audiobook, we review the requirements for successful GLP-1 drug development, from the perspective of preclinical studies, clinical trials, manufacturing, and bioanalysis. Exclusive case studies are also presented.

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.