Common Concerns for Production, Analysis and Research

1. Accountability

Accountability is a mainstay of industrial bioscience. Accountability includes not only "perfect" record-keeping and documentation, but extensive knowledge of procedures, hardware and methods. Operation limits for methods and equipment are established through validation studies and "routine" production is often the result of years of development.  In the manufacture of the products of bioscience, how you conduct the procedure is as critical as what you actually manufacture. There must be comprehensive accountability for all steps of production, analysis and quality control.

2.  Record Keeping

        Lab Note Books:

Specific organizations will have specific methods for recording data in "notebooks". Some institutions are rather casual about format, while others expect complete compliance with respect to format, content and authorization for data entry. The following is a fairly relaxed description of the regulations for one laboratory notebook style.

                Example Laboratory Notebook Requirements:

All work is to be recorded in a hardbound book, with permanent, numbered pages completed during the work period. This is to ensure that data is never misplaced or "illegally substituted" after the fact. The rule of thumb is: write it down and leave it.

1. All work must be clearly titled and described, including calculations, methods and results. This high level of organization is protection against later reviews, audits, etc. With each experiment clearly written up in an organized fashion data retrieval is relatively easy.
2. All hardware / chemicals are to be identified by manufacturer, lot # and expiry dates. Again complete accountability is required: you must be able to account for the "history" of each component you have used (i.e. whether a component was past its’ expiry date). This is a standard review item during audits.
3. Dates of daily standardization and calibration data of appropriate equipment must be included. If you have used specialized hardware that can be calibrated, (i.e. calibration is required to ensure proper functioning) the hardware must have a sticker indicating "last and next due" calibration. (This may not be possible for some of our laboratory equipment).
4. Each page must be signed (bottom corner). This is to ensure you and no-one else prepared / conducted this work or entered the data. It also implies that you are responsible and accountable for all work on that page.
5. Each page must be dated (top corner). To promote record retrieval.
6. Mistakes are crossed out with a single line and initialed beside the error. You may make hundreds of "writing errors / mistakes" but if each one is signed off correctly that is perfectly acceptable.
7. All entries are made in permanent ink: no pencil, white out etc., may be used.
8. Absolutely no pages may be removed.

    Included below are some scanned example pages of a laboratory notebook containing numerous errors. Can you find them?

Errors:

1. White-out may have been used to alter date

2. Feb 29/99 does not exist

3. A correction in the Introduction is scribbled out (require single stroke)

4. Chemicals (TRIS/NaOH) lack Lot numbers and expirary dates.

5. Distilled water is over three months old.

6. pH meter lists no serial number or calibration date.

7. pH buffers list no manufacturer.

8. pH buffers list no expiry date.

9. No reference provided for "manufacturer's instructions".

10. "Results" crossed out but unsigned.

11. Signature is unreadable.

Error types:

    When activities are conducted in the industrial biosciences there are sure to be occasional errors / mistakes. While an un-regulated institution may not be overly concerned about the method used to correct mistakes, others are require an exact accounting of error type. After crossing out the error (single stroke) many facilities require more than an initial: codes describing the specific error type are often used in order to help pinpoint and alleviate consistent mistakes. Some example "error types" might include:

	incorrect entry
	incorrect date
	calculation error
	hardware / equipment error
	late submission
	transcription error
	unauthorized entry

       These errors (and many others) will have a specific number code to describe them and require a date, initial or signature. Often the signature of a third-party (i.e. supervisor) is required for closure. By keeping track of systemic errors promptly many problems are avoided later on.

        Forms / Formal Documentation:

With products often destined for human consumption and medical purposes most analytical procedures and processing steps require a high level of precision. It is critical exacting procedures are maintained between different personnel, different shifts and production runs (Lots).  Comprehensive instructions are provided, typically as "master documents" such as SOP’s (standard operating procedures) and STM’s (standard test methods). This type of documentation is prepared through the quality system and undergoes extensive review (on many levels) to provide highly descriptive and specific work instructions. These documents usually are configured to provide not only the actual processing / analytical "treatments", but also to provide a knowledge of the purpose, scope, responsibilities, technical definitions as well as the supporting (related) documentation and necessary flow of information. Below is a list of some of the potential "master document" contents:

        Example SOP/STM Contents:

	Document originator
	Reviewers
	Dates of incorporation into Quality System
	Responsibilities
	Technical Definitions
	Equipment
	Chemicals
	Actual Work Instructions
	Forms / Processing Records
	Related Documentation / SOP’s / STM’s

These considerations are assembled into a master document. An example layout of one style of master document is presented below. "Generic" example steps are partially included.

         Example S.O.P. / Form Documentation:

 Document Title:

Document Number:

Issue Date: Supersedes: New

Revision Date: ________

Document Originator / Reviser:                                   

_________________________________

Signature Dept. Date

I have reviewed this document and find it accurate and complete:

Date:            /                                           

Date:           /                                            

This document has been approved as a Master Document.

Date:          /                                             

Quality Manager

This is an OFFICIAL COPY; a true reproduction of the MASTER DOCUMENT. It has been checked for accuracy and approved for use.

Date: ______________

Issued by:___________________

 

1.0 PURPOSE:

1.1 The purpose of this document is to describe in detail the…..

2.0 SCOPE:

2.1 The scope of this document includes:….

3.0 RESPONSIBILITY:

3.1 It is the responsibility of the Position Title to:

4.0 DEFINITIONS:

4.1 Definition 1 …

4.2 Definition 2…

5.0 MATERIALS AND EQUIPMENT:

5.1 Materials:

                                    5.1.1 Chemical 1….. (Lot #, Product #, handling)

                                    5.1.2 Chemical 2…..

5.2 Equipment:

5.2.1 Hardware 1…

5.2.2 Hardware 2…

6.0 PROCEDURE:

6.1 Initial Preparation:

6.1.1 Prepare a ……….

6.1.2 Add the …….

6.1.3 Filter the solution to….

6.2 Primary Steps:

6.2.1 Measure the…..

6.2.2 Adjust the pH to ……

6.2.4 Centrifuge at ___ G / min and…

6.2.5 Resolublize the …..

6.3 Second Treatment to remove remaining contaminants:

6.3.1 The conductivity is ….

6.3.2 Filtration to …

6.3.5 Pass the filtered solution….

6.3.6 Analyze the pass fraction by SDS-PAGE to determine….

7.0 RELATED DOCUMENTS:

7.1 Refer to DOC# XX-XXX.

7.2 Refer to DOC#XX-XXX.

8.0 RECORDS:

8.1 In-process forms

9.0 ATTACHMENTS AND EXHIBITS:

9.1 Attachment or Form #:       Title:          Number:

             EXAMPLE WORK FORM:

TITLE / Number 

Operator:_____________________________ Date:_______________

Objective:___________________________________________________

Column Type:_____________________ Initial Flow Rate:_______________

Step	Measurement	Initial
BATCH DATA	Batch:________________	________
	pH:_________	________
	mS:_________	________
	MF to:_______	________
	Sample Taken: Y	________
PREPARATION	Cleaner Vol:______(L)	________
	R.O. rinse (L):_______	________
	pH 3.5 Buffer(L):______	________
	Resin Vol:______(L)	________
	Final pH:_______	________
	Final mS:_______	________
	Tubing Integrity: Y	________
LOADING	Total :_______	________
	Total Vol.:________(L)	________
	Flow Rate:________L/hr	________
WASH	Pass Vol.:________(L)	________
	Sample Taken: Y	________
ELUTION	Eluant Vol.:_______(L)	________
	Column Clean: Y	________
	Sample Taken: Y	________
CLEANING	Cleaner Vol:______(L)	________
	R.O. rinse (L):_______	________
	Buffer1 (L):______	________
	Buffer2 (L):______	________

Production Supervisor:________________________

Quality Supervisor:___________________________

         Process deviations (PD’s), non-conformance reports (NCR’s)

Despite the best methods, equipment and attention to detail there will almost certainly be unexpected result complications during bioscience processing. There is an organized method of recording such events: as "process deviations"(PD); or as non-conforming product" (NCP), etc. The intention is to accurately document changes in the process / treatment or causes of the deviation, and to maintain an accurate record of the product / activities which are "out of specification". Sign-off on this type of document will certainly require supervisory sign-off and likely the involvement of the analytical and /or quality systems personnel.

This documentation should not be considered a shortcut around standard operating procedures and associated documentation, but should be reserved for product or steps which unexpectedly fall outside the documented specifications. These type of documents may be originated by production, analytical or quality personnel.

3.  Computer Proficiency

Computer proficiency falls under the category of a "nearly-essential" peripheral skill. While computer skills may not have bearing on a particular job function, the ability to offer professional communications and data presentations are highly valuable. New documents are continually being developed, procedures are modified, and batch and maintenance records updated. The employee capable of performing these tasks will have substantially more to offer.

   Q: What are the basic requirements of "computer proficiency"?

 

Report Writing: the bioscience professional should be able to create, edit and manipulate documents using standard word-processing programs such as "WordPerfect" or "Word"

Tables: as part of the document writing skills, there should be an ability to quickly summarize results / data in a Table format for review and communication.

Graphing: the bioscience professional should be able to present results / data in a variety of graphing formats, typically through a "spreadsheet" program such as "Excel". This allows the determination of trends and the application of basic statistical methods to data

Trend Analysis: use of a computer statistical program such as "Minitab" or "Stat 101" can allow teams to spot subtle differences in processing / methods. As well, Databases such as "Access" allow the production data to be manipulated to compare and contrast selected hardware, process steps and performance from different batches / Lots.

Internet Skills: these communications skills have become more an more important. From the desk-top computer the biotech professional can locate and communicate with suppliers, resolve technical problems and seek out relevant professional assistance.

 4.  Skills Check-List for Employment in Biosciences

 

	Adequate technical training
	Professional Integrity in technical functions: reporting actual "results" at all times
	Understanding of the roles the production, analytical and quality personnel
	Understanding of "complete accountability"
	Ability to produce and maintain highly accurate records for all activities
	Ability to report, communicate and present data using computer software, internet, and other contemporary media.
	Desire to perform an individual job function which contributes a larger final goal.

While having these skills by no means guarantees even the most gifted individual employment with a particular institution, there is no question that candidates possessing these skills make the decisions of management much easier.

Please contact the instructor for SOP assignment # 1