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.

Issue 35 ― Critical Considerations for the Safe and  Compliant Manufacture of Highly Potent Drugs

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.

Issue 36 — Nonclinical Studies in Cell and Gene Therapy

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.

Issue 37 — Quantitative PCR and Droplet Digital: Analysis for Your Gene Therapy Programs

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.

Issue 38 — Optimal Preclinical Formulation and Drug Product Manufacture

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

Issue 39 — Considerations for Nonclinical Dermal Studies: Advancing to Phase I

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

Issue 40 — Analytical Testing: Maximizing API Bioavailability

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.

Issue 41 — Immunomodulation Assessments for Clinical Trials

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.

Issue 44 — The Importance of Cytokine Release Assays to Derisk the Development of Immunomodulatory Drugs

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.

Issue 45 — Discovery Studies: An Agile Approach to Early Data for Quicker Decisions

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.

Issue 46 — Spray-Dried Dispersions

As an end-to-end CRO/CDMO, we have expert knowledge in all early stages of drug development, and we’re sharing that knowledge with you in The Altascientist: The Audiobook. 

Each issue is a deep dive into a specific area of early-phase drug development, providing insider tips, considerations, and case studies. 


Altasciences is a 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.

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