INVITATION TO SUBMIT A RESEARCH PROPOSAL ON AN ASHRAE RESEARCH PROJECT 1399-TRP, Survey of Particle Production Rates from Process Activities in Pharmaceutical and Biological Cleanrooms (Re-bid) Attached is a Request-for-Proposal (RFP) for a project dealing with a subject in which you, or your institution have expressed interest. Should you decide not to submit a proposal, please circulate it to any colleague who might have interest in this subject. Sponsoring Technical Committee: TC 9.11, Clean Spaces Budget Range: $260,000 may be more or less as determined by value of proposal and competing proposals. Scheduled Project Start Date: April 1, 2012 or later. All proposals must be received at ASHRAE Headquarters by December 15, 2011. Electronic copies must be sent to rpbids@ashrae.org. Electronic signatures must be scanned and added to the file before submitting. The submission title line should read: XXXX-TRP, Research Title and Bidding Institutions Name (electronic pdf format, ASHRAEs server will accept up to 10MB) If you have questions concerning the Project, we suggest you contact one of the individuals listed below: For Technical Matters Technical Contact E. Mitchell Swann 3 Station Square Suite 100 Paoli, PA 19301 Phone: 610.640.9609 E-mail: Swann@MDCSystems.com

For Administrative or Procedural Matters: Manager of Research & Technical Services (MORTS) Michael R. Vaughn ASHRAE, Inc. 1791 Tullie Circle, NE Atlanta, GA 30329 Phone: 404-636-8400 Fax: 678-539-2111 E-Mail: MORTS@ashrae.net

Contractors intending to submit a proposal should so notify, by mail, fax or e-mail, the Manager of Research and Technical Services, (MORTS) by November 30, 2011 in order that any late or additional information on the RFP may be furnished to them prior to the bid due date. Proposals may now be submitted electronically. Electronic submissions require a PDF file containing the complete proposal preceded by signed copies of the two forms listed below in the order listed below. ONLY electronic proposals are to be sent to rpbids@ashrae.org.

All other correspondence must be sent to ddaniel@ashrae.org and mvaughn@ashrae.org. Hardcopy submissions require 1-signed original in the same order. In all cases, the proposal must be in the hands of the ASHRAE MORTS by 8 a.m. EDT December 15, 2011.

The following forms must accompany the proposal:

(1) ASHRAE Application for Grant of Funds (signed) (2) Additional Information for Contractors (signed)

ASHRAE reserves the right to reject any or all bids.

1399-TRP, Survey of Particle Production Rates from Process Activities in Pharmaceutical and Biological Cleanrooms State of the Art (Background) There have been great strides in the technology of in use, in room particle and aerosol measurement. However accurate readings are still not available across an entire room instantaneously. The sample time is inversely proportional to the sample rate. While this monitoring can greatly aid the fine tuning necessary to more efficiently operate a cleanroom, the lack of good data during the design stage can result in oversized and inefficient systems. There have been efforts made in the past to gather data on particle generation rates and their impact on cleanroom performance1 2 3. However this information has been very process specific and not assembled or disseminated in a fashion that makes it easily accessible to building systems engineers. Thus, there is an information gap which has yet to be filled across a broad spectrum of cleanroom based industries and what data is available is often difficult to obtain. Preliminary discussions with representatives from major pharmaceutical companies and industry associations have yielded positive results and a willingness to support this research. Objective The intent of this research project is to gather empirical data on particulate generation rates for various cleanroom processes. That empirical data, correlated to the surveyed activities and operations will then be used to develop a design guideline which will show a range of particulate generation rates for different cleanroom operations. This guideline will help engineers, owners and contractors to arrive at a better design solution which meets the required performance levels but does not yield an oversized or inefficient system. The guideline would be included in the Handbook Chapter or in a separate Cleanroom Design Guideline if such a document were to be published by ASHRAE. As there is no other compendium of particle generation rates across the affected industries, we anticipate that this guide would take the dominant position in the marketplace. Scope This research projects scope is limited to measurement, data collection and cataloging particulate generation data from various cleanroom process activities. It is not intended to survey or catalogue particulate generation rates from gowning materials or procedures or from principally human activities in the cleanroom (walking, writing, equipment set-up or disassembly, etc.). The intent is to gather data from representative firms across the spectrum of cleanroom life science user industries pharmaceuticals, biotechnology products, blood and plasma processing. While recent regulations have required certain types of food processing to be done in cleanroom conditions (under HACCP regulations), we have excluded food processing from this study due to the wide array of processed products and methodologies and the relative newness of that industry to the cleanroom regime. Once the data is collected, the project will shift into the development of a compendium of the data such that particulate generation rate ranges can be ascertained for the surveyed processes. Where appropriate, factors will be included for processes which can be performed in both open (un-shrouded) and closed (shrouded or contained) formats. The final task will involve the presentation of the research data in a tabular form similar to those mentioned for internal equipment loads mentioned above.

1 Results of IES Cleanroom Flow Modeling Exercise Kuehn, Pui and Gratzek Journal of the IES March- April 1992.

2 A Statistical Study on the Design of Particle Count Measurements FUKUTSU, YAMADA, KOIZUMI and SHIMO - Journal of Aerosol Research, VOL.14;NO.1 1999 3 Characteristics of Particles Generated from Conveyors and Development of a Particle Collection Device for Clean Elevators NORIKAZU, YOSHIO, HITOSHI and HIROYUKI - Journal of Aerosol Research, VOL.14; NO.4; 1999

The particle size range that we propose this research to address is 0.10 m to 1 m. This will cover the most reasonable range of particles from just above Class 10 (ISO Class 2) to well above Class 100,000 (ISO Class 5) and will cover a particle range sufficient for HEPA filters to 95% (MERV 16) filters. Particles will be categorized as viable and non-viable to distinguish between simple particulate matter and those particles which could pose a biological threat. Chemical composition of each particle will not be addressed as this is very dependent on actual in-situ process parameters. Overview of Major Tasks: The basic scope of services to complete this project are as follows: Task 1: Literature Search for previous studies. The investigators shall provide a written report on their

findings including recommendations for what/how to include information developed in prior programs into this research project.

Task 2: Prepare a list of cleanroom-intensive industries; compile a list of processes and activities that

could be considered generic across each respective industry. Task 3: Conduct interviews with the participating companies or organizations4 to validate or amend the

list of processes5 and to evaluate how the companies execute their clean operations. Task 4: Develop reasonable ranges or rates of particle generation for each range of particle sizes

(minimum of 3) these process activities based on their interviews with the participating companies or organizations.

Task 5: Perform field measurements of particle generation rates during the processing, manufacturing

and assembly operations in the pharmaceutical, biotechnology and medical device industries at the appropriate operational space conditions for each range of particle sizes. (minimum of 3). Where particle generation rates can be determined by empirical data provided by the process operators and which has been deemed to be representative of the conditions desired in the research survey, the successful bidder shall alert the Project Monitoring Team for approval prior to accepting the third party data.i

Task 6: Compile field measured data in such a way as to present particulate generation rates, or a range

of rates (for each of a minimum of 3 particle size ranges), for the processes measured. The completed tables shall be sent to the participating companies or organizations for review and comment.ii

Task 7: Create a series of tables that present reasonably expected ranges of particle generation for

several ranges of particle size for typical industry operations within typical firms.iii Research procedures and protocols shall meet or exceed the requirements described in: IEST-RP-CC014.1: Calibration and Characterization of Optical Airborne Particle Counters IEST-G-CC1001: Counting Airborne Particles for Classification & Monitoring of Cleanrooms IEST-G-CC1003: Measurement of Airborne Macroparticles IEST-G-CC1004: Sequential-Sampling Plan for Use in Classification of the Particulate

4 Investigating team shall interview no less than four and no greater than 8 companies.

5 Processes must include but shall not be limited to: granulation, tablet pressing, coating, encapsulation, blending,

mixing, milling, printing, liquid filling, BFS processes, blister packaging and cartoning.

Deliverables: a. Intermediate Reports and Deliverables Shall Include:

List of facilities to be investigated List of interviews conducted List of process equipment technical specifications (manufacturer, model, function, key utility services, age of equipment) Schedule for Field Measurements Preliminary results after each measurement investigation The Project Evaluation and Monitoring Team will require status reports and updates at the conclusion of each major milestone in the project schedule but not less than 3 times per year.

Intermediate Submissions, Progress, Financial and Final Reports, Technical Paper(s), and Data shall constitute the only deliverables (Deliverables) under this Agreement and shall be provided as follows: b. Intermediate Submissions, Progress and Financial Reports

Intermediate Submissions: Progress Report #1: List of Facilities; List of Interviews; Schedule for Field Measurements; List of equipment technical specifications & processes. Progress Report #2: Findings after first field measurement including assessment of field measurement protocols and recommendations on improving future filed assessments.

Written Supplemental Progress Reports: preliminary results after each field measurement investigation.

The Investigative Team shall proceed to any subsequent phase of the work only after having received written notice of the PMS approval of the submitted Progress Report. Progress and Financial Reports:

Progress and Financial Reports, in a form approved by the Society, shall be made to the Society through its Manager of Research and Technical Services at quarterly intervals; specifically on or before each January 1, April 1, June 10, and October 1 of the contract period.

Furthermore, the Institutions Principal Investigator, subject to the Societys approval, shall, during the

period of performance and after the Final Report has been submitted, report in person to the sponsoring Technical Committee/Task Group (TC/TG) at the annual and winter meetings, and be available to answer such questions regarding the research as may arise.

c. Final deliverables

The final deliverables will include the following:

Particle generation rate table(s) for each of minimum of three particle size ranges. Survey reports from participating operators including detailed particle counts (sources may remain anonymous if so requested). Written description of the processes sampled.

A written report, design guide, or manual, (collectively, Final Report), in a form approved by the Society, shall be prepared by the Institution and submitted to the Societys Manager of Research and Technical Services by the end of the Agreement term, containing complete details of all research carried out under this Agreement, including a summary of the control strategy and savings guidelines. Unless otherwise specified, the final draft report shall be furnished, either electronically or hardcopy format (6 copies) for review by the Societys Project Monitoring Subcommittee (PMS).

Tabulated values for all measurements shall be provided as an appendix to the final report (for measurements which are adjusted by correction factors, also tabulate the corrected results and clearly show the method used for correction).

Following approval by the PMS and the TC/TG, in their sole discretion, final copies of the Final Report will

be furnished by the Institution as follows: -An executive summary in a form suitable for wide distribution to the industry and to the public. - One unbound copy, printed on one side only, suitable for reproduction. - One bound copy -Two copies on CD-ROM disks; one in PDF format and one in Microsoft Word. d. HVAC&R Research or ASHRAE Transactions Technical Papers

One or more papers shall be submitted first to the ASHRAE Manager of Research and Technical Services (MORTS) and then to the ASHRAE Manuscript Central website-based manuscript review system in a form and containing such information as designated by the Society suitable for publication. Papers specified as deliverables should be submitted as either Research Papers for HVAC&R Research or Technical Paper(s) for ASHRAE Transactions. Research papers contain generalized results of long-term archival value, whereas technical papers are appropriate for applied research of shorter-term value, ASHRAE Conference papers are not acceptable as deliverables from ASHRAE research projects.. The paper(s) shall conform to the instructions posted in Manuscript Central for an ASHRAE Transactions Technical or HVAC&R Research papers. The paper title shall contain the research project number (1399-RP) at the end of the title in parentheses, e.g., (1399-RP). All papers or articles prepared in connection with an ASHRAE research project, which are being submitted for inclusion in any ASHRAE publication, shall be submitted through the Manager of Research and Technical Services first and not to the publication's editor or Program Committee.

e. Data

Data is defined in General Condition VI, DATA

f. Project Synopsis

A written synopsis totaling approximately 100 words in length and written for a broad technical audience, which documents 1. Main findings of research project, 2. Why findings are significant, and 3. How the findings benefit ASHRAE membership and/or society in general shall be submitted to the Manager of Research and Technical Services by the end of the Agreement term for publication in ASHRAE Insights

The Society may request the Institution submit a technical article suitable for publication in the Societys ASHRAE JOURNAL. This is considered a voluntary submission and not a Deliverable. Technical articles shall be prepared using dual units; e.g., rational inch-pound with equivalent SI units shown parenthetically. SI usage shall be in accordance with IEEE/ASTM Standard SI-10.

Level of Effort

RP - 9902 Survey of Particle Generation Rates from Various Cleanroom Operations

to Determine Appropriate Dilution Ventilation Rates

Principal Investigator

@ $125 per hr Assistant Investigator

@ $45 per hour

Task(s) Task

Duration (weeks)

Person(s) per week

Costs Person(s) per week

Costs

Task 1: Literature Search

2 0.2 $2,000.00 1 $3,600.00

Task 2: Compiling List of Industries &

Processes 2 0.2 $2,000.00 1 $3,600.00

Task 3: Interviews 4 0.4 $8,000.00 2 $14,400.00 Task 4: Field

Measurement of Particle Generation

Rates

16 0.2 $16,000.00 4 $115,200.00

Task 5: Analysis of Field Data

10 0.4 $20,000.00 2 $36,000.00

Task 6: Preparation of Tabular Data

3 0.4 $6,000.00 2 $10,800.00

Task 7: Preparation of Final Report

4 0.4 $8,000.00 2 $14,400.00

Totals 41 $260,000.00 $62,000.00

$198,000.00

Project to be completed within 24 months of Notice to Proceed Other Information to Bidders: Within the life science industries there has been research done and data collected on this subject. However, many firms consider this information proprietary as it has been gathered expressly related to their processes and equipment. In addition, organizations like ISPE, PhRMA and PDA which are industry associations that cooperate to advance and enhance the performance of those industries. However, the results of these efforts can be difficult to obtain, especially for consulting engineers who are not members of those organizations. Their work is also very much focused on the needs and/or concerns of their members. Thus it may not address the broad spectrum of users in which ASHRAE should consider its materials. Such organizations can be good places to begin the investigation into what research has been done and where that information can be found. ASHRAEs international standing and imprimatur of excellence will aid and ease any interface with organizations such as ISPE or the PDA. Proposal Evaluation Criteria 1. Experience with Cleanroom Industries and Processes 25%

Indicate what types of cleanrooms and processes the bidder has actively participated in within the last 5 years.

2. Industry Alignment 20%

Indicate what other contracts, clients or projects the bidder is working on which are or may be related to cleanrooms, cleanroom industries and cleanroom user organizations

3. Research Excellence 25% Organizations reputation in the industry for unbiased, technically robust research and reporting of

findings. 4. Probability of contractor's research plan meeting the objectives of the Work Statement 25% Based on methodology and resources committed to the effort, what is the likelihood of this project

fulfilling the goals set forth in this Work Statement? 5. Student Involvement 5% Indicate the degree programs, level of advancement; intended level of study and most probable

timeframe for program completion of each student to be employed in executing the project. Conflicts of Interest: Report along with the bid any and all contracts, assignments or relationships which involve in a financial manner those cleanroom based industry organizations, companies or other entities (including governmental and non-governmental organizations and consortiums) which are currently in effect, pending or have completed within the 18 months preceding the submission of this proposal. ANY FAILURE TO DISCLOSE SAID RELATIONSHIPS WHICH ARE DISCOVERED AFTER THE AWARD OF THIS CONTRACT WHICH, IN THE RESEARCH PROJECTS MONITORING COMMITTEES ESTIMATION CONSTITUTE A CONFLICT OR POTENTIAL CONFLICT OF INTEREST WILL RESULT IN IMMEDIATE TERMINATION OF THE SERVICE PROVIDER WITH NO GROUNDS FOR APPEAL OR RECOMPENSE FOR OUTSTANDING INVOICES AT THE TIME OF DISCOVERY. References 1. Results of IES Cleanroom Flow Modeling Exercise Kuehn, Pui and Gratzek Journal of the IES March-

April 1992. 2. A Statistical Study on the Design of Particle Count Measurements FUKUTSU, YAMADA, KOIZUMI and

SHIMO - Journal of Aerosol Research, VOL.14;NO.1 1999 3. Characteristics of Particles Generated from Conveyors and Development of a Particle Collection Device

for Clean Elevators NORIKAZU, YOSHIO, HITOSHI and HIROYUKI - Journal of Aerosol Research, VOL.14; NO.4; 1999

4. Particle Counting Basics Using Airborne-Particle Counters for ISO certified Cleanrooms BELEW, Bill BioProcess International, September 2006.

5. ISO Standard 14644 Cleanrooms and Associated Controlled Environments 1999. 6. Greening our Cleanrooms Tools to Help Us Improve Cleanroom Energy Performance - (7/1/2006)

Future Fab Intl. Volume 21; by Phil Naughton,

i When empirical data from the operator is used as the basis for the survey, additional field measurements (a minimum of two for each particle size range) shall be taken and compared to the data provided to check the current operation against the data provided. When field measurements are to be taken by the investigators, there shall be a minimum of six runs taken at each of the operating conditions. The six runs shall be scheduled with no less than 1 hour between runs and shall use a quantity of sample points appropriate for the operation being measured. Each run shall measure particle generation rates for a minimum of three particle size ranges.

ii The primary goal of the user group review is to insure that no proprietary information is inadvertently leaked out in the final data.

iii The information will be similar to the design data for load calculations found in ASHRAEs Fundamentals Handbook, Chapter 26, Non-residential Air-Conditioning Cooling and Heating Load, i.e. Table 4 Heat Gain from typical Electric Motors, Table 8 Recommended Rate of Heat Gain from Restaurant Equipment or Table 9 Rate of Heat Gain from Selected Office Equipment. The table is not intended to identify the state of the art production techniques used to minimize particle generation, nor is it to be based upon the worst of class techniques used in antiquated, dilapidated facilities which are far below industry standard. These tables will be included in the HVAC Applications Chapter on Clean Spaces for use by the engineering community to inform and improve upon the design process.