June 2012
By Bill Lydon – Editor
This article about the conversion of production lines from single product to multiproduct, which ultimately creates flexible manufacturing pharmaceutical plants, is the fifth article in a series covering the recent annual Pharmaceutical Automation Roundtable (PAR).
I had the privilege of attending the Pharmaceutical Automation Roundtable as an observer in November 2011. This PAR was hosted by Johnson & Johnson in Spring House, PA, with Dave Stauffer, Terry Murphy, and Joel Hanson of Johnson & Johnson participating.
Lead automation engineers from various parts of the world attended the invitation-only, two-day event. This is the most knowledgeable group of automation professionals gathered in one place at any one time focused on discussing automation issues. A range of companies participated including Abbott, Amgen, Biogen Idec, BMS, Genentech, Genzyme, Glaxo, Imclone, Johnson & Johnson, Eli Lilly, Lonza, NNE Pharmaplan, Novo Nordisk, Pfizer, and Sanofi-Aventis.
The PAR was founded about 15 years ago by Dave Adler and John Krenzke, both with Eli Lilly and Company at the time, as a means of benchmarking and sharing best practices for automation groups among peer pharmaceutical companies. The group specifically does not discuss confidential or proprietary information, cost or price of products, price or other terms of supply contracts, or plans to do business or not do business with specific suppliers, contractors, or other companies.
The individual PAR group members have a wealth of practical knowledge and knowhow to share with other participants, truly learning from each other.
Topics are agreed upon prior to the meeting and a member with make a presentation on their organizations views and approach to the topic. After this presentation others comment on their organizations situation.
The presentation focused on automation to support the trend toward flexible manufacturing with multiproduct production lines. The presenter pointed out that in their company fill/finish lines are often multiproduct already today, the next most likely multiproduct area are clinical lines with typically 4-6 products a year, and commercial lines (high volume) with typically 2-4 products per facility. In addition, they are turning commercial facilities into dual clinical/commercial which is an even more complex challenge.
- Keep batch recipes simple for each product and strive for common CIP (Clean In Place) and SIP (Sterilization In Place) recipes.
- Minimize recipe variables as much as possible along with good parameter naming conventions.
- The large phases for single product designs are typically low cost for a single product but do not provide recipe flexibility.
- Flexibility for unit to unit transfers and communications is often overlooked in single product design but is very important for multiproduct production.
- Multiproduct design must also address operational requirements including SOPs (Standard Operating Procedures), work orders, manual vs. automated steps, HMI screens, messaging, batch status, operations reviews, product context, and user acceptance testing while maintaining simplicity.
In order to support more flexibility, work towards good modular S88 design with smaller phases for distinct functionality or process steps.
Regression testing is important to be sure each product in a multiproduct facility is not impacted to insure product integrity and quality. Also risk assessments become paramount and may span areas or units previously not considered.
Product changeover time and cost need to be considered in the design since it directly impacts labor, operating costs, and opportunity costs. For example, are changeovers done on planned shutdowns or are they required at other times?
“The goal is be able to add products with only a recipe change but we are not there yet,” said the presenter. This facility has a fourth and fifth product that will be added in the near term.
- Simplify phase and batch recipe code.
- Naming conventions need to be reconsidered to be more equipment specific, not tied to single product process, for example “Chrom skid 1605” rather than “Protein A Chrom skid.”
- Don’t be afraid to break phase classes at unit boundaries.
- Simplify shared equipment where possible.
In some cases it makes sense to break classes to reduce complexity or allow more flexibility.
For example, does CIP need to be batch based?
The following comments came out of the discussion by PAR members on this topic:
The shift to multiproduct manufacturing across the globe is here to stay and requires good upfront, top down design thinking centered on S88 concepts. It seems clear that investing in sound, front end loaded engineering of facility conversions from single to multiproduct production yields overall lower lifecycle cost and far less head-aches for all.
Your thoughts and comments are welcomed.
