Practical Guide for setting up Good Laboratory Practices
Quality Control Laboratories are required to :
- Demonstrate the reliability of obtained results and
- Ensure the traceability of all laboratory duties
Practical Guide for setting up GLP’s Personnel Facilities
Materials & Consumptions Computerization
Reliable results & traceability of raw data Hygiene/Safety Qualified reference standards Qualified reagents Self-inspection & quality audit Instruments Material
Treatment of results
Training Samples Documents Qualification General Procedures Validated protocols Specification
Facilities adapted Maintenance Calibrated
instruments
Qualified
apparatus
Recording
Data
validation
OOS/OOT
Check
Calculation
examined Glassware
cleaned:Q&V
Computerised systems validated
Treatment of Analytical Data
Analytical Data Processing
Pre-requisite Laboratory Practices and Principles Raw Data
Personnel
Qualification Equipment qualified
Reagents , Standards References qualified Analytical
methods
validated Adapted facilities
Pre-requisite Laboratory Practices and
Principles
Sound record keeping
Importance of sampling
Must provide representative data
Traceable and reliable reference standards
Appropriate performance of the analytical system Equipment qualification (calibration)
System suitability tests
Control samples
Appropriate validation of the analytical procedure
Treatment of Analytical Data
Raw Data
Definition
Numerical values read and transcribe manually or automatically (ex.
balances, burettes etc…)
Analytical data obtained with organoleptic control (ex. Assessment of the coloration, odor, turbidimetry)
Spectra, Chromatograms, curves of titration and other data
measured and obtained in the shape of a paper or plates from an
instrument of measurement (IR, UV, AAS, TLC, HPLC, GC, Titrators etc..)
Application
For each analytical method from European Pharmacopoeia or not :
Raw Data are in the shape of Numerical Values, Observation
Records or Graph records.
Types of GMP Documentation Raw Data
Raw Data :
The original record information on which all further actions or decisions are based
All data must be :
Permanent
Legible
Accurate
Traceable
Dated (and sometimes
timed)
Checked for accuracy
Accessible Raw Data includes :
?Production records
?Test laboratory ?Notebooks ?Chromatograms
?Charts
?Original print-outs ?Computer files
?Log book entries
?Any GMP system record entry
Treatment of Analytical Data
Raw Data
The tests performed should be recorded and the records should include at least the following data :
Dates of testing
Identification of the persons (initials of the persons who performed the testing &
initials of the persons who verified the testing and the calculations , where
appropriate - visa - signature)
Reference of the samples (name, batch number, internal identification number
etc..)
References to the relevant specifications and testing procedures
Test results, including observations and calculations and reference to any
certificates of analysis
Other information according to the cases :
Identification of the equipment (necessary if several identical equipment are
available)
Computerized system (software, version, etc…)
Identification of references materials used
Sequence of collecting the data
Raw Data
Traceability (GLP from OCDE 1997)
“All the data obtained during the study must be recorded directly, quickly, accurately and legibly by the relevant person. The data must be signed or initialed and dated. Any changes made in the raw data must be put on record as well in order not to mask the former data : the relevant person must explain the reasons for the change with the date, signature or initials.”
Raw Data
Keeping records / Archives
Any reliable means of safely conserving all the data for a period of time is permitted (paper, microfilm, photographic means,video, electronic computer systems etc…). All raw data must be kept for the length of time specified by the QC laboratory in accordance with the local legislation.
According to EU GMP Chapter 6, January 2006 :
Any Quality Control documentation relating to a batch record must be
retained for one year after the expiry date of the batch and at least
5 years after the batch release.
For legal reasons, it is mandatory to keep all GMP documents for 10/11 years at least
Raw Data
Keeping records / Archives (cont)
In the case of Recall, it is mandatory to keep all data (Recall
and Return files) for 20 years .
For some kinds of data (e.g. analytical tests results , yields,
environmental controls, …) it is recommended that records be kept in a manner permitting trend evaluation
In addition to the information which is part of the batch record, other original data such as laboratory notebooks and /or
records should be retained and readily available
Raw Data
Raw Data is validated if :
Requirements of pre-requisites are completed
System suitability tests of the method, if existing, are
satisfactory (SST)
No breakdown, no error of handling noted during the operation The use of statistical calculation could be also a help for the
validation of raw data (distribution of experimental data ;
variability, confidence intervals, trends, outliers)
Treatment of Analytical Data
Raw Data
Calculation
Direct treatment by the operating system: the raw data can be exploited directly to establish the final result (graphs, values, percentages etc…)
>>>>>>>>the operating system must be validated
Treatment by the operator : to ensure the integrity of raw
data; careful attention should be paid to capturing the raw
data; choosing and using properly the correct calculation
formula, as well as the transcription of the results (dated and signed by the operator)
Treatment of Raw Data Operating
system of Raw Data
Calculation (cont.)
Calculation of the average of several raw data figures : an internal laboratory rule must be defined in order to
determine the significant digit to be retained for the
intermediate results before calculating the average and rounding.
Treatment of Raw Data Operating
system of Raw Data
Rule for Rounding (Eur.Ph.)
“To determine conformity to numerical limit, the calculated value of the result of a test or an assay is first rounded to the number of significant figures predefined. Then the last digit is increased by 1 when the truncated part is equal to or more than 5 ; if the truncated part is less than 5 no change is made”.
In a practical situation, for intermediate results, it is not necessary to keep more digits than the number of significant digits.
Treatment of Analytical Data Operating
system of Raw Data
Example : Titrimetric Assay
Acceptance limits ( 4.0- 4.5 mg/tab.)
Numerical values : 4.234– 4.247- 4.314- 4.365
Average = 17.160/4 = 4.29
Rounding average = 4.3mg/tab.
Treatment of Analytical Data
Significant Figures
Determined by :
Measuring scale+one extra digit (estimation)
Digital instrument output (last digit assumed to be estimated)
Precision of the analytical procedure
Significant figures after calculation :
Addition or subtraction : smallest number of decimal places 10.2 mg/ml+0.235mg/ml = 10.4mg/ml (to 1 decimal place)
Mult. Or division : smallest number of significant figures
83.5/(100-15.45%) = 98.8%
Treatment of Analytical Data Significant Figures and rounding Only final result is rounded
Rounding by the first non-significant figure only < 5 → truncation
10.2 mg/ml + 0.235 mg/ml = 10.435 mg/ml → 10.4 mg/ml
5 → last significant figure +1
83.5 / (100-15.45%) = 98.75813% → 98.8%
Treatment of Analytical Data
Operating system of Raw Data Verification
“The results should be recorded and checked to make sure
that they are consistent with each other. Any calculations
should be critically examined” (EU GMP January 2006)
The verification must be done by a second person(signature and date). The verification of the results must included all the analytical data obtained (calculations, chromatograms etc…)
as well as the electronic data.
The top GMP Observations in QC
1. Quality control unit procedures
2. Data Integrity
3. Training
4. OOS management
5 Stability on time
6 Documentation management
7. Batch laboratory tests
8 Sampling management
9. Equipment calibration
10.Equipment cleaning and maintenance procedures –