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A powerful idea for pharmaceutical product development is contained in an article titled, Consider a new approach to pharmaceutical development, authored by Pradir Ki Basu, Ronald A Mack, ,and Jonathan M. Vinson available at

http://findarticles.com/p/articles/mi_qa5350/is_199908/ai_n21444525

Hereunder, Kilomentor discusses aspects of their core idea, but these comments can only be followed after reading the original article.

Much of the article presents arguments supporting the importance of cost efficiently discovering a synthetic method, scaling it up and putting into production a process for manufacturing a new pharmaceutical. This is the pharmaceutical business with the actual marketing and selling stripped away. Its importance to profitability does not need to be debated.

The present authors are concerned about the efficient execution of the plan that starts after the identification of a biologically active target that is a candidate to be a commercial drug and proceeds to the validation of manufacture that molecule at commercial scale.

The new approach that they propose positions ‘process vision’ as the core concept. It is the definition and exemplification of ‘process vision’ which is the article’s most significant accomplishment. The authors identify the defining characteristics of the process vision at different places in the article but for me, I cannot say I adequately understood it until I drew particular phrases together in my notes.

· “The process vision satisfies all essential requirements, including those for safety, quality, waste minimization, cost, time, and operability.”

· “The process vision is neither the process with maximum yield nor the one that gives maximum product purity…..it is neither a chemist’s vision, nor an engineer’s vision; it is not even the vision of the chemists and engineers together.”

· “It is a vision a vision that all stakeholders in development, manufacturing and marketing can share…..”

Reading between the lines and amplifying certain aspects, the process vision might be a policy statement that provides as a starting point, desirable standards by which team members of each stage of the plan (laboratory process, kilo lab, pilot plant, and manufacturing facility) strive to meet their downstream colleagues’ concerns from the outsell of their work.

The authors make this clearer with specific examples of the unique orientation and emphasis that players at the different stages have and which they want to bring into early assessment, early inevitable cross purposes, and early compromise or conflict resolution. They write, “Chemists think in terms of steps, reactions, yield, purity, and so on; engineers in terms of unit operations, physical properties, heat load, and the like; manufacturing personnel in terms of unit operations, in terms of throughput, waste, control issues and plant modifications that may be required to run a process; and marketing people in terms of net present value of the product, how much it can sell for etc.”

For me, what the authors are somewhat ambiguous about is the mechanism they recommend for achieving this ‘process vision’ even though over and over again in the article they return to this same theme:

“It is important ….to get stakeholders to develop….agreed-upon objectives of process development.”

“communication among….personnel is critical during process development.”

“We need to…. provid[e] development team members with systems or tools to facilitate communications among different disciplines.”

“Unless the manufacturing team is involved in the process development, they will not have confidence in the scale-up”.

“…manufacturing and commercial input at this stage [late stage discovery] is essential for choosing the optimum processing route”.

“Team members need to be involved setting targets for cost, manufacturability, waste and emission loads, development time….”

“These alternatives must be evaluated based on….criteria agreed upon by all stakeholders….”

“If stakeholders are involved in planning experiments, it’s likely that more useful data could be collected from fewer experiments.”

For me these snippets hint at or outright propose two different strategies.

One can try to bring a diverse project team, with participation beginning with late stage R&D and including representatives all the way up to marketing, together frequently enough to work out priorities and make decisions even at the experimental program level.

Alternatively, one can establish some sort of median or normal or starting-point performance criteria addressing the main, recurring concerns of process development, manufacturing, and marketing which will serve as a process vision statement that will act as a proxy for the multiform interests of the entire downstream project team and continuously represent their standard concerns to upstream collaborators.

According to this meaning, a process vision statement would be a tool commanding corporate authority that would continuously challenging upstream groups with the standard core concerns of the downstream members.

The authors marvelously illustrate this challenging throughout their article. What I interpret them to be saying is that the problem is not that different elements of the project team have concerns which inevitably seem to operate at cross purposes; but that the team members will reach solutions that satisfy all parties, so long as the area of tension is discovered early enough.

Kilomentor has a strong preference for the second alternative. Use of a process vision statement as a proxy for the perspectives and concerns of downstream project groups seems preferable to using meetings of a large group with the frequency needed to actually direct even the collection of particular data. For a company’s drug product projects to be successful and on-time, any process’s strategy must not conflict too greatly with the psychological needs and private professional goals of the individual team members. The people downstream in the project, whether they be in process development, manufacturing, or marketing, simply will not give a project the attention it needs until it arrives at the phase where they are being held singly and personally responsible. They are too busy concentrating their attention on what is on their plate already and extinguishing the fat that is already in the fire. This is human nature! Besides, pharmaceutical product projects can go on so long that some participants can realistically expect to no longer be involved when a late-stage discovery project limps into manufacturing or marketing. People may hope or plan to outrun the difficulties.

Equally problematically, the up stream professionals, working at a particular phase of the work on their own turf, would require an uncommon personal modestly to accept without rancor face-to-face demands that particular questions be answered on a priority basis.

A corporate ‘process vision’ statement takes the personalities and egos out. At the same time, the standards proposed by a process vision statement would command authority and yet not be carved in stone. They would exist to bring a persistent awareness of particular concerns. They would bring those different needs, which may be pulling at cross purposes to early attention, and they can be expected to bring the affected team members together to create or negotiate a solution.

This excellent thought provoking article by Basu, Mack and Vinson contains other important ideas which I hope to look at in later blogs.

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