Pharmaceutical manufacturing is heavily regulated, though standards designed to guide the selection of measurement and analytical instrumentation for sterile processes are not completely defined. To fill the void, some companies — and even individual plants — have created their own internal guidelines for instrument selection and verification to meet U.S. Food and Drug Administration current good manufacturing practices (cGMPs).
With the need for a comprehensive set of standards clear, the American Society of Mechanical Engineers (ASME) developed bioprocessing equipment standards specific to the requirements of hygienic industries. The resulting ASME BPE (Bioprocessing Equipment) standard addresses materials, design, fabrication, testing and certification.
Prior to the initial ASME BPE release, pharmaceutical manufacturers relied on other sanitary standards such as 3A, first developed for the dairy industry. These were used in conjunction with internally developed guidelines. Unlike the 3A standards, which establish requirements for a relatively narrow set of applications, ASME BPE uses broader applications as a starting point. Over the same time frame in Europe, the European Hygienic Engineering and Design Group developed its own standards to certify equipment and promote effective designs for food and pharmaceutical products.
In the past, pharmaceutical manufacturers have been able to pick and choose the criteria required for specific applications, and then communicate the resulting expectations across facilities, suppliers and inspectors. But with ASME BPE, biopharmaceutical manufacturers are finding it easier to coordinate activities and comply with FDA requirements and cGMPs.
The initial ASME BPE release developed general guidelines applicable to instrumentation and other areas, but it wasn’t until 2012 that a specific section was added to cover instrumentation, primarily with respect to bioburden and cleanability. Subsequent updates have added more detailed guidelines for specific instrument types.
Part GR (General Requirements) defines the scope and includes six sections:
1. Manufacturer’s quality programs
6. Terms and definitions
These general guidelines apply to all types of equipment including process instrumentation,
and also cover some of the less detailed areas. New releases are expected to expand the extent of instrumentation coverage.
Following defined cGMPs, ASME BPE and traditionally accepted practices, users and instrumentation vendors must take into account a number of factors such as:
• Instrument technology type
• Surface design and finish (internal and external)
• Metallic alloy selection (corrosion resistance)
• Non-metallic composition and surface finishes (internal and external)
• Wetted versus external surfaces
• Placement and mounting of instrumentation
• Temperature range requirements
• Suitability for SIP
• Gaskets, seals and welds
• Smart versus traditional instruments
• Need for redundancy
Pharmaceutical plants and instrumentation suppliers have to consider these standards when designing devices for sanitary industries.
TYPES OF PROCESS ENVIRONMENTS
Most pharmaceutical plants have multiple process units to manufacture products. Since there can be many manufacturing approaches used for pharmaceutical products, there are many types of processing units. Approaches can vary from unit to unit with major differences in the measurement, cleanability and bioburden control required for each. There are also varying levels of precision required for processes automation, and concern about potential contamination. In spite of the differences, their degree of importance to the larger operation is often interlinked.
Some processes need to operate in very narrow temperature ranges and within very specific chemical environments to maintain critical fermentation. On the other hand, some basic active ingredients can withstand much wider latitude without affecting critical attributes. Sanitation and the need for cleanliness also vary within the range of basic pharmaceutical requirements, but typically sensitivity to manufacturing parameters and contamination go hand-in-hand.
For purposes of this discussion, we will divide processes into high-, medium- and low-sensitivity environments (see Figure 1). Each of these areas has its specific needs related to equipment configuration and operational practices, which has direct impact on instrumentation selection and configuration. These are, of course, generalizations for purposes of comparison and to guide the thought process of selection. Any actual application has to be examined and configured appropriately.