Never Too Early For QbD

Excipients make up more than 90 per cent of each pill or tablet we consume but have not been a major focus of regulators in the past. With a significant number of drug recalls traced to inconsistent quality of excipients and faulty product design, the Quality by Design approach must be implemented as early as possible in the drug development lifecycle. Recent regulations and initiatives have attempted to modernise this segment of the pharma industry.

- Viveka Roychowdhury

Good manufacturing practices (GMPs) are the foundation of the pharmaceutical sector, as they assure the patient that her medicines actually contain what they should, and will not harm her health further. Adherence to GMPs guarantee quality medicines and regulators like the US Food and Drug Administration (FDA), and European Medicines Agency (EMA), have taken the lead to demand more stringent quality standards each year. India’s drug quality watch dog, the Central Drugs Standard Control Organization (CDSCO) has also increased the level of its scrutiny of late. (See a previous story: http://www.expressbpd.com/pharma/editors-note/a-springcleaning-at-the-cdsco/398184/)

These quality standards have evolved from testing the quality of the finished final product to testing the inputs as well as design of the entire production cycle, right from the formulation development stages. In other words, not quality by testing (QbT) of the final product but quality by design (QbD) of the process, including sourcing input ingredients of the desired quality.

Industry observers point out that a lot has changed in terms of reviewing abbreviated new drug applications (ANDAs). Regulators have on occasion resorted to the Refusal to Receive (RTR) option if the application does not contain evidence that the products were developed in compliance with the principles of QbD.

In some cases, if serious lapses in GMP compliance of the facility are found in the application, a complete response letter or its equivalent which is a warning letter (WL) may be issued. Thus a new approach in which an integrated quality team reviews dossiers, focussing on the possible GMP deficiencies of the concerned manufacturing plant, is very crucial. This will close the gaps between drug development and scale up.