Over the decades, advancements in treatment procedures have brought about necessary amendments to the Regulatory framework. From Active Pharmaceutical Ingredient (API) identification to its placement on the patient’s side table, the core of innovating novel treatment protocols revolves around three (03) fundamental characteristics, including safety, effectiveness, and timely availability to the patient population. While patients explore the luxury of effective treatment, another segment of the population with unmet medical needs suffers at large. The European Medicines Agency (EMA) has introduced expedited routes like the PRIME - PRIority MEdicine, and the Innovative Licensing and Access Pathway (ILAP) as tools to promise accelerated approvals of novel medications. To monitor the quality of the novel therapy, the quality testing of drug substances plays a major role in the drug development lifecycle. Module-1 (regional administrative information), Module-2 (quality - overall summary), and Module 3 (quality) of the dossier include information upholding the optimum quality standard of a drug product.

As regulators gear up to explore expedited pathways for unmet patient needs, innovators ought to recognize the significance of Chemistry, Manufacturing, and Controls (CMC) through a Quality by Design (QbD) approach. QbD is an enhanced approach to drug development that aims to deliver quality medicines by employing statistical, analytical, and risk-management methodologies to design, develop, and manufacture medicines. QbD elements can be sourced back to the International Council for Harmonization (ICH) guideline Q8, comprising the pharmaceutical development section outlining the scientific understanding to support the establishment of specifications and controls.

While understanding the requirements to be fulfilled under the CMC section, biopharmaceutics, and pharmacokinetic characteristics, including the in-vivo analysis, are a considerable precursor to recognizing a molecule with a stable and effective product. The CMC section of the Investigational New Drug (IND), New Drug Application (NDA), and the Abbreviated New Drug Application (ANDA) dossiers are obligated to mention details regarding the procedures employed throughout the manufacturing process by the Health Agency. The compiled clinical/non-clinical data records provide the necessary data to support stability and demonstrate the permissible limit and analysis procedures used to ensure the authenticity, strength, quality, purity, and nature of the drug substance and drug product.

Understanding the industry’s dynamic nature, regulators have re-defined the approaches to pharmaceutical drug development via enhanced QbD protocols that represent streamlined process validation and quality controls for small and large molecule groups. The EMA and the United States Food and Drug Administration (USFDA), as a joint initiative, support parallel assessment of sections involving QbD parameters of an application.

The QbD approach for an ideal CMC section is a promising approach for drug development because it includes:

  • A systematic approach to development
  • Multivariate experiments and design of experiments
  • Manufacturing process and space design
  • Focus on control strategy and robustness of the process
  • Process Analytical Tools (PAT) used for feedforward and feedback process control
  • Risk-based control strategy & potential real-time release
  • Preventive lifecycle management and continuous improvement

Ideal drug development protocols are meant to bridge the gap within the population with unmet medical needs. Technological advancements and dynamic procedures have simplified the techniques to predict the success or failure of a given molecule. Such initial screening allows streamlining efforts in the direction of better therapeutic choices available for patients to choose from. At Freyr, we understand your desire to achieve best-in-class CMC documentation for your next application. Our experts can cater to your pre-and post-authorization CMC and lifecycle management needs, including changes in manufacturing site, addition/deletion, Marketing Authorization Holder (MAH) transfers, eCTD/CTD dossier preparation, drug license renewal applications, re-registration dossiers, and Certificate of Suitability (CEP) updates. To know more about Freyr’s services, and compliance best practices, contact us today.

Facilitated regulatory pathways can avoid the lag faced by innovators in gaining market access. What kind of facilitated pathways are available in the EU? Listen to how can you fast-track EU market entry from our experts? Know more.


Akancha Singh
Senior Associate


Related Posts by Category