Advanced qualification of pharmaceutical excipient suppliers by multiple analytics and multivariate analysis combined.
Pharmaceutical excipients have different functions within a drug formulation, consequently they can influence the manufacturability and/or performance of medicinal products. Therefore, critical to quality attributes should be kept constant. Sometimes it may be necessary to qualify a second supplier, but its product will not be completely equal to the first supplier product. To minimize risks of not detecting small non-similarities between suppliers and to detect lot-to-lot variability for each supplier, multivariate data analysis (MVA) can be used as a more powerful alternative to classical quality control that uses one-parameter-at-a-time monitoring. Such approach is capable of supporting the requirements of a new guideline by the European Parliament and Council (2015/C-95/02) demanding appropriate quality control strategies for excipients based on their criticality and supplier risks in ensuring quality, safety and function. This study compares calcium hydrogen phosphate from two suppliers. It can be assumed that both suppliers use different manufacturing processes. Therefore, possible chemical and physical differences were investigated by using Raman spectroscopy, laser diffraction and X-ray powder diffraction. Afterwards MVA was used to extract relevant information from each analytical technique. Both CaHPO4 could be discriminated by their supplier. The gained knowledge allowed to specify an enhanced strategy for second supplier qualification.
Laboratory for Liquid Products, Merck Serono, Frankfurter Str. 250, 64293 Darmstadt, Germany; Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001 Lisbon, Portugal. Electronic address: alexandra.hertrampf@external.merckgroup.com.
A
A
Hertrampf
Laboratory for Process Development, Merck Millipore, Frankfurter Str. 250, 64293 Darmstadt, Germany. Electronic address: heike.m.mueller@merckgroup.com.
H
H
Müller
Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001 Lisbon, Portugal. Electronic address: cardoso.menezes@tecnico.ulisboa.pt.
J C
JC
Menezes
Laboratory for Liquid Products, Merck Serono, Frankfurter Str. 250, 64293 Darmstadt, Germany. Electronic address: thorsten.herdling@merckgroup.com.
T
T
Herdling
D002130:Calcium Phosphates / Q000737:chemistry / Q000592:standards; D002626:Chemistry, Pharmaceutical / Q000592:standards*; D004345:Drug Industry / Q000592:standards*; D005079:Excipients / Q000737:chemistry* / Q000592:standards*; D008855:Microscopy, Electron, Scanning; D015999:Multivariate Analysis; D010316:Particle Size; D011786:Quality Control; D014961:X-Ray Diffraction
D002130:Calcium Phosphates; D005079:Excipients; C485829:calcium phosphate, dibasic, anhydrous
Calcium hydrogen phosphate (PubChem CID: 24441); Multivariate data analysis; Pharmaceutical excipients; Process analytical technology; Quality control strategy; Supplier qualification