International Journal of Pharmaceutics 491 (2015) 1
Contents lists available at ScienceDirect
International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm
Editorial
Pharmaceutical quality assessment
In this issue of the journal, Yu and Woodcock (2015) detail the changes launched by the United States’ Food and Drug Administration (FDA) to optimise the agency’s quality oversight through the formation of the new Office for Pharmaceutical Quality (OPQ). To the regular readers of this journal the complex nature of the evaluation of new and generic chemical and biological active agents, novel excipients, materials and a multiplicity of formulations, themselves often complex, will not be a surprise. What is important in this paper – which is not an official FDA document but the views of two who have made significant personal contributions to drug regulation – is their description of the trajectory to this advanced and holistic approach to the evaluation of medicines. This is derived from an acute awareness of the significance of advances in pharmaceutical science and technologies and indeed manufacturing processes to the adoption of clinically relevant parameters in inspection and the setting of standards. The candor of the authors in discussing the problems encountered with established approaches is to be applauded, including the recognition that many drug shortages in the USA and elsewhere are in part occasioned by the burden of inappropriate regulation. It is many years since I was involved personally in drug regulation as a member of the UK’s Committee on Safety of Medicines and as a member and latterly Chair of its Chemistry, Pharmacy and Standards (CPS) sub-committee (until 1998), but I recall the many occasions when there was a tension between existing regulations and the clearly evident need to evolve new approaches to deal with novel delivery systems and complex drug molecules, including biologics. It is always difficult when a completely novel product appears and ingenuity is necessary in its evaluation. I do not recall that we were so aware of the effect of new manufacturing technologies on our decisions, but we were certainly aware that even subtle manufacturing changes could have clinical consequences as with the now classic 1972 example of Lanoxin digoxin in the UK (Shaw, 1974) which was my initiation. Milling techniques could lead to fatalities! CPS concentrated mainly on new drugs and their purity and stability, formulations and their advantages and disadvantages. It is sobering looking back that it was once suggested that pharmaceutical assessment could be more a box-ticking exercise than an intellectual multi-disciplinary scientific pursuit as described in the paper. Lawrence Yu and Janet Woodcock, well known to all in the field, speak with authority on many relevant and evolving issues in quality assessment. A concentration of regulatory attention on high-risk products and an emphasis on clinically relevant parameters, not parameters for their own sake or for quality
http://dx.doi.org/10.1016/j.ijpharm.2015.06.003 0378-5173/ ã 2015 Published by Elsevier B.V.
control of processes. Elsewhere Yu (2015) has simply stated that “patients deserve quality medications.” What is encouraging is the interconnection between the new offices and officers of FDA to integrate oversight of product safety and reliability, with basic research, informatics, inspection protocols, and emphasis on emerging technologies such as continuous manufacture. The wider relevance of this FDA vision is not only for those concerned with manufacture and marketing of products, but also I believe for scientists working in academic laboratories on basic and applied pharmaceutics research, one preoccupation of this journal. The lessons to be learned by those working in the area nanotechnology, for example, is that much more emphasis has to be placed on the multi-faceted characterisation of our systems (Crist et al., 2013), their stability in vitro and in vivo, the reproducibility of preparation methods, and the relevance of animal models as the basis for assessing potential human application. What is the real relevance of our size analysis, dissolution, drug release studies and biodistribution data in informing the future utility or promise? Are we instilling the holistic approach to pharmaceutical quality into our laboratory work so that results are extrapolable and relevant? We have a lot to learn. The huge implication of the work of Center for Drug Evaluation and Research is matched by its large budget and some 3450 staff, a massive resource. Its importance is not only in the United States but further afield in ensuring medicines are as reliable, safe and effective as they can be, and continuously available to patients in need. I hope that the paper generates the interest it deserves in all sphere. References Crist, R.M., Grossman, J.H., Patri, A.K., Stern, S.T., Dobrovolska, M.A., Adisshaiah, P.P., Clogston, J.D., McNeil, S.E., 2013. Common pitfalls in nanotechnology: lessons learned from NCT’s Nanotechnology Characterisation Laboratory. Integr. Biol. (Camb) 5 (1) doi:http://dx.doi.org/10.1039/c2ib20117h. Shaw, T.R.D., 1974. The digoxin affair. Postgrad. Med. J. 50, 98–102. Yu, L.X., 2015. http://www.fda.gov/Drugs/NewsEvents/ucm428298.htm. Yu, L.X., Woodcock, J., 2015. FDA pharmaceutical quality oversight. Int. J. Pharm. (in press).
Alexander T. Florence Editor in Chief UCL School of Pharmacy, University College London, UK
E-mail address: Ataylorfl[email protected] (A. Florence). Available online 6 June 2015
Contents lists available at ScienceDirect
International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm
Editorial
Pharmaceutical quality assessment
In this issue of the journal, Yu and Woodcock (2015) detail the changes launched by the United States’ Food and Drug Administration (FDA) to optimise the agency’s quality oversight through the formation of the new Office for Pharmaceutical Quality (OPQ). To the regular readers of this journal the complex nature of the evaluation of new and generic chemical and biological active agents, novel excipients, materials and a multiplicity of formulations, themselves often complex, will not be a surprise. What is important in this paper – which is not an official FDA document but the views of two who have made significant personal contributions to drug regulation – is their description of the trajectory to this advanced and holistic approach to the evaluation of medicines. This is derived from an acute awareness of the significance of advances in pharmaceutical science and technologies and indeed manufacturing processes to the adoption of clinically relevant parameters in inspection and the setting of standards. The candor of the authors in discussing the problems encountered with established approaches is to be applauded, including the recognition that many drug shortages in the USA and elsewhere are in part occasioned by the burden of inappropriate regulation. It is many years since I was involved personally in drug regulation as a member of the UK’s Committee on Safety of Medicines and as a member and latterly Chair of its Chemistry, Pharmacy and Standards (CPS) sub-committee (until 1998), but I recall the many occasions when there was a tension between existing regulations and the clearly evident need to evolve new approaches to deal with novel delivery systems and complex drug molecules, including biologics. It is always difficult when a completely novel product appears and ingenuity is necessary in its evaluation. I do not recall that we were so aware of the effect of new manufacturing technologies on our decisions, but we were certainly aware that even subtle manufacturing changes could have clinical consequences as with the now classic 1972 example of Lanoxin digoxin in the UK (Shaw, 1974) which was my initiation. Milling techniques could lead to fatalities! CPS concentrated mainly on new drugs and their purity and stability, formulations and their advantages and disadvantages. It is sobering looking back that it was once suggested that pharmaceutical assessment could be more a box-ticking exercise than an intellectual multi-disciplinary scientific pursuit as described in the paper. Lawrence Yu and Janet Woodcock, well known to all in the field, speak with authority on many relevant and evolving issues in quality assessment. A concentration of regulatory attention on high-risk products and an emphasis on clinically relevant parameters, not parameters for their own sake or for quality
http://dx.doi.org/10.1016/j.ijpharm.2015.06.003 0378-5173/ ã 2015 Published by Elsevier B.V.
control of processes. Elsewhere Yu (2015) has simply stated that “patients deserve quality medications.” What is encouraging is the interconnection between the new offices and officers of FDA to integrate oversight of product safety and reliability, with basic research, informatics, inspection protocols, and emphasis on emerging technologies such as continuous manufacture. The wider relevance of this FDA vision is not only for those concerned with manufacture and marketing of products, but also I believe for scientists working in academic laboratories on basic and applied pharmaceutics research, one preoccupation of this journal. The lessons to be learned by those working in the area nanotechnology, for example, is that much more emphasis has to be placed on the multi-faceted characterisation of our systems (Crist et al., 2013), their stability in vitro and in vivo, the reproducibility of preparation methods, and the relevance of animal models as the basis for assessing potential human application. What is the real relevance of our size analysis, dissolution, drug release studies and biodistribution data in informing the future utility or promise? Are we instilling the holistic approach to pharmaceutical quality into our laboratory work so that results are extrapolable and relevant? We have a lot to learn. The huge implication of the work of Center for Drug Evaluation and Research is matched by its large budget and some 3450 staff, a massive resource. Its importance is not only in the United States but further afield in ensuring medicines are as reliable, safe and effective as they can be, and continuously available to patients in need. I hope that the paper generates the interest it deserves in all sphere. References Crist, R.M., Grossman, J.H., Patri, A.K., Stern, S.T., Dobrovolska, M.A., Adisshaiah, P.P., Clogston, J.D., McNeil, S.E., 2013. Common pitfalls in nanotechnology: lessons learned from NCT’s Nanotechnology Characterisation Laboratory. Integr. Biol. (Camb) 5 (1) doi:http://dx.doi.org/10.1039/c2ib20117h. Shaw, T.R.D., 1974. The digoxin affair. Postgrad. Med. J. 50, 98–102. Yu, L.X., 2015. http://www.fda.gov/Drugs/NewsEvents/ucm428298.htm. Yu, L.X., Woodcock, J., 2015. FDA pharmaceutical quality oversight. Int. J. Pharm. (in press).
Alexander T. Florence Editor in Chief UCL School of Pharmacy, University College London, UK
E-mail address: Ataylorfl[email protected] (A. Florence). Available online 6 June 2015
