Pharmaceutical Regulatory Affairs: Open Access

New treatments for diabetes are always exciting in the beginning but as experience grows their position in management becomes less certain. This review focuses on DPP4 inhibitors and their place in management of type 2 diabetes. Although hypoglycaemia is rarely an issue, the effectiveness in reduction in blood sugar is greatest at the higher blood sugar levels, hence much of the value of using DPP4 inhibitors rests in the target HbA1c chosen for the individual patient.

Progress in genome and proteome research led to a deeper insight in differential gene expression processes. This required the use of sensitive and specific tools in diagnostics; also new promising patient-specific therapy attempts are conceivable. Nucleic acids were up till now a critical goal for diagnostic applications and therapeutic interventions, but in future they can serve as highly sequence-specific tools in molecular diagnostics. Examples for diagnostic Molecular Imaging modalities are the analysis of metabolic processes which can lead to customized therapeutic approaches (“Targeted Therapy”). The solid phase peptide synthesis SPPS is considered as an excellent tool in the individualized medicine with nucleic acids which increasingly play a key role as a drug. This requires new properties of the nucleic acid-based drugs, contiguous to the stability in biological systems, a high variability by combination with functional peptide-based molecules or with reformulated drugs or imaging components. The multifaceted application spectrum is dependent on the patients’ individual differential gene expression profiles or on the medical questionnaire. Here we show a new synthesis strategy able to circumvent ligations steps and to enhance the yields in the SPPS technology by use of a novel disulfide-containing monomer. This molecule acts as a disulfide linker which can overcome the common occasional losses occurring during established coupling reactions, like disulfide-bridge formations.

In recent years, adaptive designs have recaptured attentions in the clinical research society as they can improve the flexibility and efficiency of conducting a clinical trial and increase the chance of trial success. However, adaptive trials are complex to design and often accompanied with various degrees of statistical, procedural, logistic and regulatory challenges. This article provides a general overview of adaptive designs with attentions to the discussion on the basic concepts, classification, application scope and principles with current understanding of regulatory agencies throughout the article. The adaptive designs in the exploratory, seamless and confirmatory stages are separated discussed with some common types briefly described respectively in order to account for the differences in regulatory impact and concerns. The strategic regulatory, statistical and operational considerations on how to use adaptive design are presented. It is hopeful that more innovation and collaboration made by the industry, academia, and regulatory agencies could promote the application of adaptive designs and transform the drug development.

Regulators from countries at all levels of income struggle to protect the public from the dangers of poor-quality (counterfeit and substandard) medicines. In particular countries with limited resources are at higher risk because of weak regulations, insufficient personnel, or  laboratories with poor infrastructure and a lack of equipment required to perform quality control analysis. A systematic approach is needed to address these gaps.

A stepwise process was used to design medicine quality monitoring programs in numerous countries in Africa, South America, and Southeast Asia. The experience gained in these countries resulted in the development of the Three-level Approach for performing quality control of medicines throughout the supply chain.

The approach consists of three successive, complementary, and increasingly complex levels of analysis: The first level includes visual and physical inspection to assess package and insert conditions and information as well as the physical characteristics of the actual medicines. The second level consists of rapid analytical tests that assess a limited number of quality attributes and can easily be performed in the field by trained personnel. The third level involves quality control testing according to the product’s registration specifications and is performed in an appropriate laboratory setting by experienced and trained analysts.

The Three-level Approach offers regulators in limited resource countries, a cost-effective high-throughput methodology for quality monitoring that produces valid and trustworthy results. The approach strengthens medicines quality assurance systems by allowing better regulation of the pharmaceutical market, which ultimately reduces the prevalence of poor-quality medicines.