Aaron Cote, Ph.D, Eric Sirota, Aaron Moment, Ph.D.
In order to ensure the quality of a pharmaceutical drug that will be dosed orally as a tablet or capsule containing crystalline active pharmaceutical ingredient (API), it is critical that the crystal form and physical attributes (particle size, surface, area, bulk density, etc.) be well-controlled, since these may impact the drug’s bioavailability and stability as well as the ability to effectively formulate the API into a finished drug product.
Rolf Brickl, Ph.D.
In early phases of development, only small amounts of the active pharmaceutical ingredient (API) are available. With difficult drugs however, many different formulations are necessary to achieve adequate bioavailability. Therefore, low API consumption for each formulation creates a substantial developmental advantage. This can be achieved by miniaturized equipment for the most relevant pharmaceutical technologies. Until a few years ago, the commercially available equipment required minimal batch sizes of 50 – 100 g for nearly all formulation technologies. Number of small scale equipment increased considerably in the meantime, but in most cases, the basic technologies are still designed for large scales, only the formulation part is smaller. Therefore, this equipment is still very expensive, heavy, and requires a lot of lab space and cannot be located easily into containments which is necessary for toxic or highly active APIs. Therefore, miniaturized equipment for the most relevant form
Ryan Hutchinson, Timothy Matthews, Jimmy Sugahara
Single use technologies are widely used in biopharmaceutical
processes. Single use items such as bioprocess containers,
filters, tubing, connectors, mixers, and even bioreactors have
been used for some time and provide several benefits including:
lower capital costs, increased flexibility, and reduced validation,
cleaning, and sterilization requirements.
Peter Tattersall, Ph.D., Li Li, Ph.D., Qinggang Wang, Ph.D.
Gathering analytical data on impurities is important for early stage pharmaceutical development. In early development (phase I / II) the drug substance (DS) synthesis route, the solid state form and formulation are not final, however a HPLC method used for tracking and trending impurities is required. This information will give the process chemist / formulator understanding and enable improvement of the synthesis or formulation, setting specifications, releasing of batches, performing stability studies and determining storage conditions. While ICH guidance does not need to be rigorously followed in early stage development, it is beneficial to consider what will be required in the later stages of development [1].
Amol Mungikar, Ph.D, Madhav Kamat, Ph.D
Structural/chemical changes induced by thermal and shear
stresses during manufacture and shipping as well as potential
interactions with various contact surfaces may lead to protein
aggregation.
Jun Chen, Ph.D., Robert Mattes, Katherine Bakeev, Steve Doherty, Rick E. Cooley, Rebecca Vangenechten
JC:I think one of the trends is to re-think what the appropriate role is for PAT/NIR in the fields of pharmaceutical research, development and manufacturing scheme and how the technology can be best utilized under the current regulatory environment.
Richard A. Storey, Jane Norris, Ph.D.
Freeze drying (lyophilization) is a process used widely for improving the stability of labile pharmaceuticals. It is the formulation of choice for compounds unstable in solution or for heat labile pharmaceutical products and biological compounds. During the formulation of freeze dried formulations, it is critical to ensure the reconstitution of the lyophile is rapid and complete.
Frederick G. Vogt, Ph.D., Glenn R. Williams, Ph.D.
Analysis of the solid state plays a key role in modern drug
development during pharmaceutical process development and in
support of regulatory filing activities [1-3]. The analytical techniques
used in this field span the interface between physical chemistry,
materials science, surface science, and supramolecular chemistry,
and provide critical knowledge and understanding of complex
phenomena such as polymorphism, disorder in the crystalline state,
molecular-level interactions in crystalline and amorphous materials,
and the formation of defects, inclusions, solid solutions, and related
phenomena in materials.
Marc Schleh, Bill Lawrence, Tom Park, Scott Rosenthal, Ph.D., Roger Hart, Ph.D., Houman Dehghani, Ph.D.
A multipronged approach is used to ensure the safety of mammalian cell-derived biotechnology therapeutics from adventitious contaminants such as viruses and mycoplasma. Extensive characterization and testing of the cell substrate, lotto- lot release testing for adventitious contaminants and viral clearance characterization of the downstream purification unit operations are integral parts of this approach. Adherence to current Good Manufacturing Practices (cGMP) and a robust raw material quality review form the cornerstones of this safety approach [1-5]. Consequently, there have been no reported cases of transmission of an adventitious agent through biotechnology derived therapeutics and as such these products have an untarnished safety record. Although very rare events, contaminations of mammalian cell culture bioreactors with adventitious agents have been reported [6-11] and present a business continuity risk. To further safeguard against such contamination events, technologies capabl