Facility Design TutorialFacility Design Tutorial

This tutorial is designed to enhance knowledge of This tutorial is designed to enhance knowledge of biotechnological/pharmaceutical processes. The topics biotechnological/pharmaceutical processes. The topics

covered within this tutorial will give preliminary covered within this tutorial will give preliminary explanations and conclusions. However, references for explanations and conclusions. However, references for

more in depth study will be provided. It is strongly more in depth study will be provided. It is strongly suggested that you investigate these references. suggested that you investigate these references.

OverviewOverview

Introduction Introduction – Description of facility design and why it is important to chemical engineers.Description of facility design and why it is important to chemical engineers.

EquipmentEquipment– This section will describe equipment considerations during facility design.This section will describe equipment considerations during facility design.

UtilitiesUtilities– This section will describe implications of facility design concerning facility This section will describe implications of facility design concerning facility

utilities.utilities.Waste SystemsWaste Systems– This section describes the role of waste disposal when developing a facility.This section describes the role of waste disposal when developing a facility.

StorageStorage– This section will discuss the impact of raw materials and final product storage This section will discuss the impact of raw materials and final product storage

on facility design.on facility design.ConclusionsConclusions

IntroductionIntroduction

The overall goal of process development is to implement a conceptual The overall goal of process development is to implement a conceptual design into a manufacturing scale. For this reason, chemical engineers design into a manufacturing scale. For this reason, chemical engineers have to consider the implications of facility design.have to consider the implications of facility design.

In facility design, the manufacturing process concept is transformed into a In facility design, the manufacturing process concept is transformed into a physical process within a facility. For this reason, a detailed block flow physical process within a facility. For this reason, a detailed block flow diagram (BFD) should be created. The facility can be designed from this diagram (BFD) should be created. The facility can be designed from this BFD.BFD.

This tutorial will describe a few of the aspects that should be taken into This tutorial will describe a few of the aspects that should be taken into consideration when designing a facility for a pharmaceutical/biotech consideration when designing a facility for a pharmaceutical/biotech product.product.

RegulationsRegulations

The pharmaceutical/biotech industry is regulated by Food and Drug The pharmaceutical/biotech industry is regulated by Food and Drug Administration (FDA). The FDA in turn sets guidelines for facility design, Administration (FDA). The FDA in turn sets guidelines for facility design, but these are only broadly define acceptable limits. The manufacturer but these are only broadly define acceptable limits. The manufacturer ultimately decides how to implement these regulations.ultimately decides how to implement these regulations.

The main regulations for facility design comes from the US Federal The main regulations for facility design comes from the US Federal Standard 209E (FED-STD-209E). This document specifically sets the Standard 209E (FED-STD-209E). This document specifically sets the standards for air handling within the facility. It defines the amount standards for air handling within the facility. It defines the amount permissible per particulate size. This limit in turn determines the permissible per particulate size. This limit in turn determines the classification of the process rooms within the facility. classification of the process rooms within the facility.

RegulationsRegulations

Facilities must also comply to current Good Manufacturing Processes Facilities must also comply to current Good Manufacturing Processes (cGMP). cGMP is a system of good manufacturing procedures and (cGMP). cGMP is a system of good manufacturing procedures and techniques that ultimately protect the patient. As the name implies, the techniques that ultimately protect the patient. As the name implies, the standard are periodically updated to reflect changes within the industry. standard are periodically updated to reflect changes within the industry. For facilities, the regulations are defined in the US Code of Federal For facilities, the regulations are defined in the US Code of Federal Regulations, specifically, 21 CFR 211.42 - 211.58.Regulations, specifically, 21 CFR 211.42 - 211.58.

EquipmentEquipment

One of the main considerations for the development of facility is the One of the main considerations for the development of facility is the equipment needed for the manufacturing process. One should assess what equipment needed for the manufacturing process. One should assess what is needed based on the BFD.is needed based on the BFD.

Since this project is a retrofit of an existing facility, consideration should Since this project is a retrofit of an existing facility, consideration should be taken into what existing equipment can be utilized. If the equipment be taken into what existing equipment can be utilized. If the equipment meets the specifications for the process, one should considering using meets the specifications for the process, one should considering using them. This will save the company money and time.them. This will save the company money and time.

However, many times equipment cannot be used for various reasons (out However, many times equipment cannot be used for various reasons (out of spec., intrinsic problems, etc.). At this point, new equipment should be of spec., intrinsic problems, etc.). At this point, new equipment should be purchased and incorporated into the facility.purchased and incorporated into the facility.

EquipmentEquipment

When incorporating this new equipment certain consideration should be When incorporating this new equipment certain consideration should be made. Can the equipment physically be moved into the building? Is the made. Can the equipment physically be moved into the building? Is the facility processing room(s) big enough for the equipment? Is construction facility processing room(s) big enough for the equipment? Is construction needed to build or refurbish the facility in order to accommodate the needed to build or refurbish the facility in order to accommodate the equipment.equipment.

These are just a few of the consideration a engineer must take into account These are just a few of the consideration a engineer must take into account with process equipment. Other will arise pending on the specific piece of with process equipment. Other will arise pending on the specific piece of equipment. The facility should be designed around these aspects.equipment. The facility should be designed around these aspects.

UtilitiesUtilities

Engineers should also consider the facility utilities during conceptual Engineers should also consider the facility utilities during conceptual design. Since the nature of the product is pharmaceutical/biotech , many design. Since the nature of the product is pharmaceutical/biotech , many specific systems have be considered. specific systems have be considered.

The systems include, but are not limited too, water for injection (WFI), The systems include, but are not limited too, water for injection (WFI), clean in place/steam in place (CIP/SIP), HVAC, compressed air, etc. clean in place/steam in place (CIP/SIP), HVAC, compressed air, etc. (Explanations and references are given in the ‘Information’ section of this (Explanations and references are given in the ‘Information’ section of this website). HVAC and CIP/SIP are needed to ensure human safety and website). HVAC and CIP/SIP are needed to ensure human safety and minimal product contamination. Whereas WFI and compressed air are used minimal product contamination. Whereas WFI and compressed air are used in the manufacturing process.in the manufacturing process.

Since this situation involves a retrofit, these systems may already be in Since this situation involves a retrofit, these systems may already be in place. But are they accessible for the equipment? Do they meet the place. But are they accessible for the equipment? Do they meet the specifications of the process? Will any system need to be updated or specifications of the process? Will any system need to be updated or modified? These are just a few of the questions that should be considered.modified? These are just a few of the questions that should be considered.

Waste SystemsWaste Systems

Once again, since this product is biological, there may be special Once again, since this product is biological, there may be special regulations that exists to guide this process. In addition, engineers should regulations that exists to guide this process. In addition, engineers should make sure waste treatment facilities are safe for man as well as nature.make sure waste treatment facilities are safe for man as well as nature.

It is certain that the manufacturing process will generate significant wastes It is certain that the manufacturing process will generate significant wastes associated with fermentation and purification. The facility must be able to associated with fermentation and purification. The facility must be able to dispose of these wastes effectively and safely.dispose of these wastes effectively and safely.

For biotech industries the main concern of waste treatment is the For biotech industries the main concern of waste treatment is the recombinant host. This organism may pose health threats if it is released recombinant host. This organism may pose health threats if it is released untreated into the environment. Methods of disposal vary pending on the untreated into the environment. Methods of disposal vary pending on the organism. This should be kept in mind when design the waste treatment organism. This should be kept in mind when design the waste treatment facility.facility.

Waste SystemsWaste Systems

So, where will these wastes go? Are there facilities already existing that So, where will these wastes go? Are there facilities already existing that can handle these wastes? Are they sufficient in size and capacity? Are a can handle these wastes? Are they sufficient in size and capacity? Are a few more questions that should be assessed when designing the waste few more questions that should be assessed when designing the waste treatment section of the facility.treatment section of the facility.

Broad guidelines exist for waste systems as documented by the US Code of Broad guidelines exist for waste systems as documented by the US Code of Federal Regulations (CFR). As mentioned earlier these codes include:Federal Regulations (CFR). As mentioned earlier these codes include:

– 40 CFR Part 26140 CFR Part 261

– 40 CFR Part 26440 CFR Part 264

StorageStorage

Storage of raw materials and products also has special consequences in the Storage of raw materials and products also has special consequences in the pharmaceutical/biotech context. These materials have to be quarantined pharmaceutical/biotech context. These materials have to be quarantined when raw materials are received and after product packaging. This ensures when raw materials are received and after product packaging. This ensures that the materials avoid contamination while also minimizing human that the materials avoid contamination while also minimizing human exposure. During this time, the new materials are properly labeled and exposure. During this time, the new materials are properly labeled and tested before dispensing into the facility. The packaged product, on the tested before dispensing into the facility. The packaged product, on the other hand, awaits shipping.other hand, awaits shipping.

When the facility become functional these raw materials and final products When the facility become functional these raw materials and final products will need a place for storage. This is yet another consideration an engineer will need a place for storage. This is yet another consideration an engineer must make during facility design.must make during facility design.

Do these storage rooms already exist? Can a existing room(s) be modified Do these storage rooms already exist? Can a existing room(s) be modified to accommodate these materials? Is there a need to build a new storage to accommodate these materials? Is there a need to build a new storage facility? An engineer should ponder these questions.facility? An engineer should ponder these questions.

ConclusionsConclusions

The design of a biological facility is multifaceted. Implementation of the The design of a biological facility is multifaceted. Implementation of the processing equipment is just the first step in designing an effective facility. processing equipment is just the first step in designing an effective facility. The aforementioned information is a starting point for considering The aforementioned information is a starting point for considering decisions about facility design. Ultimately, particular decisions will be decisions about facility design. Ultimately, particular decisions will be based on manufacturing needs, the BFD, and the existing facility.based on manufacturing needs, the BFD, and the existing facility.

ResourcesResources

[1] Facility regulations: [1] Facility regulations: www.fda.govwww.fda.gov– 21 CFR Part 211: 21 CFR Part 211:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfhttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfmm

– FED-STD-209EFED-STD-209E[2] Waste treatment regulations:[2] Waste treatment regulations:– 40 CFR 26140 CFR 261– 40 CFR 26440 CFR 264

[3] Industrial contact: Bob Perrone - Fluor Daniels.[3] Industrial contact: Bob Perrone - Fluor Daniels.

[4] Cole, Graham C. [4] Cole, Graham C. Pharmaceutical Production FacilitiesPharmaceutical Production Facilities. Taylor & . Taylor & Francis Inc., 1998.Francis Inc., 1998.