One of the final, but most important, tasks a research and development (R&D) organization must do is to help make a product ready for manufacturing,the technology transfer stage in new product development. Information about how to make a product in laboratory systems must be scaled up to production volumes.
In the pharmaceutical industry, many scales of production often exist. The scales can vary from micrograms to metric tons, with small samples being manufactured for trials or marketing tests and large production runs after government approval.
Often the different production scales are performed at separate facilities or laboratories. All of these issues make it vital for a company to be able to define how to make a product in a comprehensive, unambiguous manner.
The Instrumentation, Systems and Automation Society's (ISA) S88.01 and the International Electrotechnical Commission (IEC) 61512-01 standards introduce the concept of general recipes as the repository for product manufacturing definitions. A general recipe is intended to be the primary document used by process engineers in the generation of equipment-specific master recipes. Site recipes are local versions of the general recipe, containing the elements to be produced at the site, local languages, local units of measure and variations for local material availability.
A general recipe defined
General and site recipes can be represented as process- and material-dependency diagrams. Usually engineers with a deep understanding of the target process cell layout perform the transformation from the general or site recipe to the master recipe for each process cell.
The target process cell equipment can vary in unit layout, automation level, physical properties and process control capability, so considerable variation in master recipes is possible. Because of this variation, master recipes are not the best way to exchange manufacturing definitions between sites. General recipes, which are independent of specific unit layout, automation levels and equipment specifics, provide a better way to describe manufacturing definitions. General recipes can be used as controlling documents across sites, defining the chemistry and physics that must be accomplished to manufacture a product.
Another way to view a general recipe is as a contract between R&D and manufacturing,a binding agreement between the two parties. In this case, it is an agreement on how to produce a product. To be useful, the contract must be both comprehensive and unambiguous.
General recipes involve a variety of elements, including the process definition, process stages, process operations, process actions and equipment constraints. A general recipe process is defined using process stages. Process stages contain one or more process operations, and process operations are accomplished using one or more process actions.
As an example, consider a method for documenting the process operations, process actions and equipment constraints of a general recipe's process stage. The purpose of this documentation is to provide the author of the master recipe with a sufficient definition of the manufacturing process so it can be converted into a master recipe procedure, bound to the specific units or class of units. In this example, the equipment constraints are associated with a process stage definition, and the process operations are defined as an organizing structure of process actions.
Define process actions
A key element of the contract with manufacturing is the definition of the process actions that are used to make up general recipes. The process stages and process operations will vary based on products, but they should be constructed from a standardized company- or division-wide library of process action definitions. The process actions define the basic production process capabilities of the company (or division) in an abstract manner. They define the processes manufacturing can perform to make products. Specific general recipes describe the order and timing of the processes to make specific products.
As with any good contract, a process action definition must define all of the assumptions and contingencies associated with its use. The elements of a process action include:
- A description of the basic functionality provided by the process action;
- A definition of any parameters that could be passed to the process action to modify or characterize its behavior;
- A definition of any information that could be returned as a result of the process action execution;
- A definition of any assumptions about the execution environment of the process actions;
- A definition of any required preconditions that must be met for the process action to execute correctly;
- A definition of any expected post conditions that must be handled as a result of the processes action execution; and,
- A definition of known exception conditions and how they should be handled.
Experience has shown that most companies or product line divisions can define their basic manufacturing process capabilities using 30 to 50 process action definitions. These definitions range from simple capabilities such as adding and mixing materials to industry- or process-specific capabilities related to separation, extraction and final material packaging.
Process actions generally can be divided into two subtypes , general and company-specific , which can be categorized further into 10 subtypes. General actions deal with adding materials, removing materials, adding energy, removing energy and setting material environments (pressure, agitation, etc.). Company-specific actions might deal with unique material preparation, material extraction, material shaping, material packaging and material testing. Each of these 10 subtypes usually has additional variations on the methods, bringing the total to between 30 and 50.
Because all general and site recipes are built from a basic set of 30 to 50 process action definitions, the task for process engineers constructing master recipes is made easier. Local site engineers need only to determine the best methods for implementing the process actions on their local equipment. The engineers then can use these best methods when constructing master recipes.
Using a well-defined library of process actions and a well-defined library of site-specific implementations can significantly reduce the amount of work required to construct master recipes. It also can reduce the variations in recipe quality resulting from the use of different authors.
The definition of the process-action library should be worked out between R&D and manufacturing. A well-documented library of process actions will reduce the ambiguity of the general recipe definition and make technology transfers faster with fewer errors.
The library of process actions should be managed tightly with controls in place to eliminate unintentional changes. Any change to the library of process actions could impact hundreds to thousands of recipes and could require re-engineering in all production plants, so changes must be controlled tightly because of their potential impact.
The second main element of a general recipe is the definition of equipment constraints. These specifications of constraints must be met by production equipment for the material to be correctly produced. Examples include constraints on the type of materials used in the production equipment and constraints on the type of heating or cooling.
Equipment constraints are employed when the equipment used for production might affect the chemistry or physics of the process. For example, the material under construction might react with the vessel, producing a contaminated product or even preventing the desired reaction. Experience has shown that most companies can characterize their equipment using between 10 and 20 equipment constraints.
Process engineers use equipment constraints to select the appropriate equipment to make a product. The general recipes identify the target equipment through its properties without specifying the exact equipment. The combination of equipment constraints and the ability to perform process actions on equipment enables the process engineer to select the best manufacturing equipment. For example, the requirement to heat a material combined with the ability to mix at the same time,and to do this in a copper-free environment,would eliminate any nonheating, nonmixing or copper vessels from consideration.
Equipment constraints also can define "hints" to production. For example, they could indicate short transfer lines are needed because the material tends to clog lines or react during transfer. Other hints could involve companywide definitions of equipment classes that are appropriate. For example, a company might characterize equipment as "Type 1 , Safe for Color Film" or "Type 2 , Not Safe for Color Film."
Library control and work flows
Because equipment constraints are used by manufacturing to select equipment, they must be well understood and contain unambiguous definitions. Equipment constraint types also should be maintained in a library so they are available to general and site recipe authors.
One method to manage process actions and equipment constraints is to apply configuration management to the definitions. Versions for each definition and states for each definition could be available. The states should be supported by a work flow process that requires sign-off approval to change the state of the object and a work flow to ensure that all parties are informed of any changes.
All in the contract
General and site recipes define a contract between manufacturing and R&D. They define the chemical and physical rules for making a product. They also define constraints on the target manufacturing equipment. The general recipe also can be a repository for other information about the product such as pictures, diagrams, chemical drawings or even laboratory notes.
The main constituents of a general recipe are process actions and equipment constraints. Experience has shown that the best way to use process actions and equipment constraints is to construct a managed library of definitions.
General recipe authors then can use these definitions. The library allows them to define how to manufacture a product unambiguously, ensuring that places to put all pertinent information exist.
Process engineers can use the process action library to define a set of best practices to implement the actions on their equipment. This allows them to build consistent, predicable recipes. A controlled library of equipment constraints provides similar advantages to recipe authors and process engineers.
This article is based on a presentation at World Batch Forum, April 2002.
Brandl is president of Cary, N.C.-based BR&L Consulting, which specializes in strategic direction, tactical execution, consulting and training in the areas of batch control, business-to-manufacturing integration and manufacturing execution system (MES) solutions for the process industries. He has been involved in MES, batch control and automation system design and implementation in a wide range of applications during the past 25 years. He can be reached at (919) 852-5322 or via e-mail at [email protected].