David Blicq firstname.lastname@example.org (update 05/15/2013) DIRECTORY I BIO I NOTICE BOARD
"Analysis" includes any activities which measure product quality at any stage of manufacture, tests to determine the quality of incoming materials, final product analysis and other types of testing. Simple analyses may be conducted by production staff as required, but often the majority of the testing is conducted by a dedicated analytical personnel specifically trained for this function. There are often extremely dedicated analytical tools requiring considerable expertise and highly focused staff.
Some analytical considerations might include:
|Specific Hardware / Analytical Tools|
|Standardization / Calibration|
|Validating Standards, Methods and Equipment|
|Cleaning, repair and maintenance of analytical hardware|
|Record keeping: documentation / forms|
|Documentation: work instructions//flow charts: SOP's, STMs|
|Process deviations (PDs), non-conformance reports (NCRs)|
- Example Hardware / Analytical Tools
Analytical systems and methodologies will vary considerably, but the overall goal remains the same regardless of the particular institution: analysis must provide clear, accurate measurement against quantifiable controls which indicate not only accurate measurements but also that the procedure is conducted within defined parameters. There are many analytical tools and we will examine only a few examples:
|Spectrophotometers are devices which pass light of an exact wavelength through a soluble liquid sample. The sample must be appropriately diluted to operate within the range of sensitivity and be compared against an appropriate "blank" solution. Spectrophotometers can provide a wide range of rapid measurements. Data can be recorded manually or through computer software.|
|Automated Analyzers include a number of fairly complex machines which automate many repetitious tasks of analysis (example TDx - Abbott Laboratories). Typically a carousel or tray of samples is prepared and placed in the unit to follow an automated protocol. The carousel / cartridge may contain references, blanks, samples or standard curves or any combination. These machines can mix, dilute, add reagents, incubate and analyze samples once a program is initiated. Some of these machines measure fluorescence, amplify genetic material (through PCR) , determine specific enzymatic activity or any other programmable function. Analytical protocols can be as per the equipment manufacturers instructions or following in-house protocols. Although automated hardware can greatly improve analytical efficiency, there is a need for considerable training as well as comprehensive cleaning and maintenance protocols.|
|Chromatography methods include HPLC (high performance liquid chromatography) and GC (gas chromatography) and other methods. These powerful analytical instruments partially immobilize specific components of a mixture pass other. Analysis is most often through dedicated hardware providing meaningful results in a short period of time. These types of methods depend on the analyst establishing a good system "baseline" / equilibrium and samples must be compared against relevant references. As expected with complex hardware, cleaning, maintenance and calibration are regular concerns.|
The study of the numerous specific hardware / tools of analysis is beyond the scope of this course, but it is worth remembering that whatever tools / methods are employed for analysis the procedures must be conducted by qualified personnel using approved methods. The use of "test samples" or "spiked samples" sent through an analytical laboratory is one way of testing procedural accuracy.
2. Standardization / Calibration
Standardization and Calibration can sometimes imply different meanings to different parties.
For the purposes of this course we will consider "standardization" to be the daily test of a piece of equipment against known traceable standards. Standardization is conducted to ensure a daily measurement / operation is conducted within clearly-defined operating limits.
"Calibration" is a less frequent but equally important test of equipment by a qualified third party. This type of measurement may involve bringing in a certified professional or, (if a company is sufficiently large) there may be an in-house calibration team.
Meticulous records are maintained for standardization and calibration records: after all, these activities ensure that all analytical procedures will be conducted using equipment operating within narrowly-defined parameters. Quality and analytical functions often overlap with respect to standardization / calibration methods and records.
For analysis to be meaningful analytical data must be referenced against known "standards". This is essential to determine if specific hardware is functioning within exact parameters for any given analysis. It is common for an analytical team to maintain a "library" of catalogued reference samples. These samples are usually finite, meaning when they run out a comparable appropriate reference sample must be used as a replacement.
Validation studies are used to validate a replacement reference material, to confirm the performance of replacement / new hardware or systems. These are highly organized studies which test the extremes of the operation as well as the expected standard operating conditions of the procedure.
Extremely precise records are needed to confirm the efficacy of validation studies: along with process deviations and non-conforming products these studies are often a focus of audits since their accuracy is essential to the quality of results affecting entire procedures.
Sampling is the process of acquiring part of a material, typically for later testing / analysis. Although this may seem simple, there must be strict guidelines to ensure a sample is pepresentative of the entire batch (material) that is supposed to represent. Let's examine the simple process of acquiring a liquid sample of a material undergoing processing in a 2000L reactor. There can be many considerations:
|quanity of sample needed to be representative|
|time period in which sample is acquired|
|depth at which sample is taken|
|sampling method (dedicated sample port vs submerged sample cup)|
|required agitation to ensure uniform dispersal|
|time period over which sample remains representative|
|sample handling / storage / transport conditions|
Obviously the simple act of taking a sample can obviously involve considerable detail. Typically, if taking a sample is important, there will be a detailed sampling protocol describing what hardware and methods are needed.
Training of analytical staff may be quite detailed since it affects all aspects of production. Training is often related to a specific test procedure can involve both theoretical as well as hands-on training. Analytical staff are expected to demonstrate proficiency before being signed-off on a particular function.
With particularly complex hardware the manufacturer may deliver training as part of a technical seminar. Other analytical training will come from supervisors with appropriate experience and background. Actual training may involve not only the procedure itself but also the required standardization, cleaning maintenance and trouble-shooting activities.
Records of all training activities must be kept up-to-date and accessible since these are also highly-auditable documents.
6. Cleaning, repair and maintenance of analytical hardware
Depending on the nature of the analytical system, analytical staff may be responsible for cleaning, minor repair and maintenance, or these activities may be left to other technicians. Cleaning may be a simple "rinse" cycle of buffer / solvent or may be a complex protocol demanding considerable time and effort. The method should meet the requirements of both the equipment manufacturer and industry itself and have well-documented evidence demonstrating procedure effectiveness.
It is also important that there is a clear understanding of what types of routine maintenance are within the scope of the analytical technicians. Analytical staff should perform their duties within established limits and be well aware of which maintenance procedures beyond their responsibility.
Complete, comprehensive records of all repair / maintenance activities must be maintained for all equipment and this is usually managed as part of the quality system.
7. Record keeping: documentation / forms
As in the production area, record-keeping and documentation is of critical importance. These records ensure the analytical information for any stage of production is readily available and accurate.
As expected, routine methods may employ simplified forms which are appropriately filled in, dated, signed / initialed by the analyst. Sign-of by supervisory personnel is common.
Analytical records may be maintained as part of the "batch records" for a particular "Lot" or production run. The location, length of maintenance and traceability of analytical records is often a shared responsibility of the analytical and quality functions.
Occasionally, a laboratory notebook will be used instead of official forms or records. All the same rules previously described for production laboratory notebooks applies to analytical notebooks. They are expected to be hardbound books with numbered pages, entries are made in ink and errors being "stroked out" with a single line and an initial / signature of the author acknowledging the error. Again, appropriate titling, dates and signatures are expected. As well, these books also remain property of the institution and may not be removed form the site as they contain critical information.
8. Documentation: work instructions//flow charts: SOP's, STMs
STMs (standard test methods) are the dedicated written testing procedure used for analyses. As with production documents, STMs are usually prepared through the quality system and are critically reviewed for accuracy. These are comprehensive documents describing each and every aspect of the test method in complete detail.
The same scope of responsibility applies to STMs and SOPs in analysis as those described in the "Production" section (Chapter 2, Section 4-5). Please refer to those examples for a review of SOP/STM details.
9. Process deviations (PDs), non-conformance reports (NCRs)
Just as in production, unexpected deviations irregularities will occasionally occur during analysis. As in production these variations must be accurately recorded as "process deviations" (PD); or as non-conforming product" (NCP), etc. The analyst must accurately document changes / variations in the analytical procedure, and to maintain an accurate record of the analyses which are "out of specification". As in production, 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.
In analysis there should not be a large number of deviations providing the method is being appropriately applied by trained personnel.