Masterstudiengang "Drug Regulatory Affairs"


Life cycle management of a marketed medicinal product in view of GMP and regulatory requirements and impact of Product Quality Reviews ***

Dr. Tatjana Reinholz (Abschlußjahr: 2007)

Language: English

In the EU, a pharmaceutical company has to deal with requirements according to the GMP and regulatory legislation. The regulatory environment has become more demanding during the last years e.g. by the “new legislation” coming into force. While for the approval of a marketing authorisation the quality, safety and efficacy has to be proven, only limited data are available at the time of submission. The data must be sufficient to predict the performance of the medicinal product in the market. As this is only possible to a certain extent, additional post-approval monitoring is necessary.

It is the task of the authorities to ensure a certain level of quality and safety of a product during life cycle according to their task to protect public health and to offer the highest possible medication to the population.

The marketing authorisation must be kept on the current level of science by introducing variations. Due to the high workload other quality-related variations are mainly introduced for economic reasons. The increasing demand of manpower for life cycle management has been perceived also by authorities. Several initiatives have been started to focus the resources on the most important, i.e. high-risk products according to the principles of risk-management.
This thesis deals with the quality aspects of life cycle management in the EU legislative regulatory and GMP environment, especially process validation, stability and Product Quality Reviews (PQRs). A valid process impacts the quality of the medicinal product and must therefore be maintained at all times during the life cycle. Stability is a prerequisite to ensure the quality during shelf life. The requirements concerning on-going stability have been introduced only lately into the GMP Guide. Additionally, stability studies may also be necessary as a consequence of changes that affect the products stability.

PQRs are intended to monitor all relevant aspects of quality of a medicinal product and additionally link these to the marketing authorisation status. They also address stability issues and the need for re-validation.

Furthermore, they monitor e.g. results from quality control and the performance of the product in the market (e.g. re-calls). It is the intention not only to collect data but to increase knowledge about the respective product. This is beneficial for the authorities as well as for the marketing authorisation holder or manufacturer, respectively.

Additionally, the increasingly restrictive regulatory environment inhibits improvement that would be a benefit for public health. Continuous improvement is only achieved if the workload, i.e. the regulatory requirements, during life cycle management is not increased further.

Currently, several concepts have been developed or are under discussion that address these issues. One example are the ICH Q8, Q9 and Q10 guidelines which offer pharmaceutical industry a higher grade of independency from the competent authorities if the product-related risk is reduced on the basis of scientific knowledge.
PQRs are helpful to perform knowledge-based risk management and also to increase the design space (according to ICH Q8) with the aim to reduce workload for both the marketing authorisation holder as well as the competent authority.
Another concept is the revision of the European variation legislation that has just been started. It is likely that an annual reporting system will be introduced into EU variation legislation in the future. Though the requirements for the prospective annual reports are indefinite at the moment, PQRs may currently cover some of those aspects.
So far, by introduction of the PQRs the quality monitoring has been partly shifted to the competent GMP authority.

In conclusion, PQRs are powerful tools not only to control and improve the quality of a medicinal product and to increase regulatory compliance but also within the framework of current changes in legislation as far as life cycle management is concerned.

Pages: 57