Services Provided by The Zlota Company

As part of our project support, in the area of Risk Analysis, The Zlota Co. provides clients with the following:

• Recommendations for the formation of a suitable team to conduct risk analysis, avoiding the selection of too large or too small groups, with possible background bias.
• Guidance for building an effective cause-and-effect diagram, in particular to avoid possible confusion ensuring the inclusion of meaningful process parameters during the brainstorming stage.
• Advice in defining ranking scales for semi-quantitative risk assessment, to be consistently used by the team*.
• A semi-quantitative method for risk analysis suitable for the project stage: one method for early, and another for late development, or for prior to technology transfer to a plant
  • For early development projects we enable rapid risk analysis, avoiding “busy work”, and spending too much time for such analysis, producing short, manageable documents summarizing the risk assessment.
• Advising in designing effective pre-DoE (statistical design of experiments) as one-variable-at-a-time (OVAT) experiments, using the fundamental science available, an important factor in determining the success of a DoE.

*Ranking scales, together with other general recommendations for a particular company are often captured in an internal guideline for QbD implementation, a suitably short document, updated as needed, which we help compile. Such internal guidelines lead to recommendations for best practices for QbD implementation in that specific organization.

For additional information please contact us.

As part of our project support, in the area of DoE, The Zlota Co. provides clients with the following:

• Guidance in the selection of a suitable group of factors to be included in a screening DoE, most importantly for the definition of the factor ranges to be used*.
• A check-list for DoE execution necessary to ensure that the data generated is suitable for statistical analysis.
• Advice regarding the inclusion of scale-independent and scale-dependent factors.
• Recommendations for the design of a screening DoE matrix suitable for the generation of the necessary process understanding using the resources available to the team.
• Clarify the best options for a DoE in early versus late development projects.
• Reconcile, as needed, the recommendations of a sponsor and those of a CRO.
• Guidance about the use of appropriate DoE software, for both the design as well as for the data analysis and interpretation, balancing statistical with practical significance.
• Advice for the use of the screening DoE results for the design, as appropriate, of an optimization (Response Surface Methodology, RSM) DoE.
• Using available (target) specifications, support for meaningful identification of “sweet spots”, and possible Design Spaces.
• Using risk calculations, guidance for meaningful proposal of a Design Space, of Potential Critical Process Parameters, and of appropriate verification experiments.
• Ensure that all DoE reports, in particular those used to support a proposed Design Space, are written in full compliance with the QbD ICH guidelines, as well as with those of various regional regulatory agencies.
• Guidance with the scale-up of the Design Space.

* Such guidance, together with other general recommendations for a particular company are often captured in an internal guideline for QbD implementation, a suitably short document, updated as needed, which we help compile. Such internal guidelines lead to recommendations for best practices for QbD implementation in that specific organization.

For additional information please contact us.

As part of our project support, in the area of chemical process scale-up, The Zlota Co. provides clients with the following:

• Guidance for the design of scale-up and/or scale-down investigations, for chemical reactions, API crystallizations and micronization processes*.
• Advice with the design of experiments aimed at identification of scale-up factors, for homogeneous as well as for heterogeneous chemical processes (solid-liquid, liquid-liquid, and gas-liquid systems).
• Clarification of the assessment of the controlling mixing mechanism in the process at stake: micromixing, mesomixing, macromixing, or a combination thereof.
• Recommendations for the use of suitable lab equipment for the execution of scale-up investigations, as well as for the effective use of Process Analytical Technology (PAT) tools aimed at developing suitable process understanding in the minimum number of experiments.
• Recommendations for the use of appropriate scale-up factors as DoE variables.
• Guidance for the building of an equipment database using suitable mixing and scale-up calculations, including guidance with the use of appropriate software for such calculations.
• Advice with the selection of suitable plant equipment (reactor, agitator) for technology transfer and scale-up, in particular for cases of multipurpose equipment, including recommended operating conditions based on the results of the scale-up investigations conducted.
• Guidance for suitable scale-up strategies for drug product process scale-up, using a meaningful blend of scale-up science and of statistical design of experiments (DoE).

* Such guidance, together with other general recommendations for a particular company are often captured in an internal guideline for QbD implementation, a suitably brief document, updated as needed, which we help compile. Such internal guidelines lead to recommendations for best practices for QbD implementation in that specific organization.

For additional information please contact us.